The menopause is accompanied by increased risk of obesity, altered body fat distribution, and decreased skeletal muscle mass. The resulting decrease in RMR should be accompanied by a compensatory change in energy balance to avoid weight gain. We aimed to investigate habitual energy intake and expenditure in pre- and post-menopausal women matched for abdominal obesity. We recruited fifty-one healthy Caucasian women, BMI >18.5 and
Griffiths AJ, Humphreys SM, Clark ML, Fielding BA, Frayn KN (1994) Immediate metabolic availability of dietary fat in combination with carbohydrate., Am J Clin Nutr 59 (1) pp. 53-59
We tested the hypothesis that when fat is ingested in combination with carbohydrate, direct release of fatty acids into the plasma may occur. Eight normal subjects ingested two meals: high-fat (80 g fat, 80 g carbohydrate, and 18 g protein) and low-fat (
DAVIES AG, POSTLETHWAITE RJ, PRICE DA, BURN JL, HOULTON CA, FIELDING BA (1984) URINARY ALBUMIN EXCRETION IN SCHOOL-CHILDREN, ARCHIVES OF DISEASE IN CHILDHOOD 59 (7) pp. 625-630 BRITISH MED JOURNAL PUBL GROUP
Hodson L, McQuaid SE, Humphreys SM, Milne R, Fielding BA, Frayn KN, Karpe F (2010) Greater dietary fat oxidation in obese compared with lean men: an adaptive mechanism to prevent liver fat accumulation?, AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM 299 (4) pp. E584-E592 AMER PHYSIOLOGICAL SOC
Moore JB, Gunn PJ, Fielding BA (2014) The role of dietary sugars and de novo lipogenesis in non-alcoholic fatty liver disease., Nutrients 6 (12) pp. 5679-5703
Dietary sugar consumption, in particular sugar-sweetened beverages and the monosaccharide fructose, has been linked to the incidence and severity of non-alcoholic fatty liver disease (NAFLD). Intervention studies in both animals and humans have shown large doses of fructose to be particularly lipogenic. While fructose does stimulate de novo lipogenesis (DNL), stable isotope tracer studies in humans demonstrate quantitatively that the lipogenic effect of fructose is not mediated exclusively by its provision of excess substrates for DNL. The deleterious metabolic effects of high fructose loads appear to be a consequence of altered transcriptional regulatory networks impacting intracellular macronutrient metabolism and altering signaling and inflammatory processes. Uric acid generated by fructose metabolism may also contribute to or exacerbate these effects. Here we review data from human and animal intervention and stable isotope tracer studies relevant to the role of dietary sugars on NAFLD development and progression, in the context of typical sugar consumption patterns and dietary recommendations worldwide. We conclude that the use of hypercaloric, supra-physiological doses in intervention trials has been a major confounding factor and whether or not dietary sugars, including fructose, at typically consumed population levels, effect hepatic lipogenesis and NAFLD pathogenesis in humans independently of excess energy remains unresolved.
Frayn KN, Summers LKM, Fielding BA (1997) Regulation of the plasma non-esterified fatty acid concentration in the postprandial state, PROCEEDINGS OF THE NUTRITION SOCIETY 56 (2) pp. 713-721 C A B INTERNATIONAL
Fielding BA, Roberts R, Bickerton A, Karpe F, Gilbert M, Frayn KN (2004) Comparison of GC-MS and GC-cIRMS for the measurement of [C-13] palmitate enrichment in a stable isotope study in vivo in man, INTERNATIONAL JOURNAL OF OBESITY 28 pp. S165-S165 NATURE PUBLISHING GROUP
Karpe E, Ruge T, Hodson L, Fielding B, Humphreys SM, Dennis L, Cheeseman J, Frayn KN (2008) Regulation of fat storage in human subcutaneous adipose tissue over a 24-hour period, DIABETOLOGIA 51 pp. S20-S20 SPRINGER
Kotronen A, Westerbacka J, Fielding BA, Wahren J, Hodson L, Seppanen-Laakso T, Suortti T, Arola J, Hultcrantz R, Castillo S, Frayn KN, Oresic M, Yki-Jarvinen H (2010) Splanchnic balance of free fatty acids, endocannabinoids and lipids in subjects with NAFLD, DIABETOLOGIA 53 pp. S104-S104 SPRINGER
Robertson MD, Jackson KG, Fielding BA, Morgan LM, Williams CM, Frayn KN (2002) Acute ingestion of a meal rich in n-3 polyunsaturated fatty acids results in rapid gastric emptying in humans, AMERICAN JOURNAL OF CLINICAL NUTRITION 76 (1) pp. 232-238 AMER SOC CLINICAL NUTRITION
DAVIES AG, PRICE DA, POSTLETHWAITE RJ, ADDISON GM, BURN JL, FIELDING BA (1985) RENAL-FUNCTION IN DIABETES-MELLITUS, ARCHIVES OF DISEASE IN CHILDHOOD 60 (4) pp. 299-304 BRITISH MED JOURNAL PUBL GROUP
Fernandez C, Lindholm M, Krogh M, Lucas S, Larsson S, Osmark P, Berger K, Boren J, Fielding B, Frayn K, Holm C (2008) Disturbed cholesterol homeostasis in hormone-sensitive lipase-null mice, AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM 295 (4) pp. E820-E831 AMER PHYSIOLOGICAL SOC
Jackson KG, Robertson MD, Fielding BA, Frayn KN, Williams CM (2002) Olive oil increases the number of triacylglycerol-rich chylomicron particles compared with other oils: an effect retained when a second standard meal is fed, AMERICAN JOURNAL OF CLINICAL NUTRITION 76 (5) pp. 942-949 AMER SOC CLINICAL NUTRITION
Frayn KN, Fielding BA, Samra JS, Summers LKM (1997) Extracellular metabolic regulation in adipose tissue, PHYSIOLOGY, STRESS, AND MALNUTRITION pp. 303-323 LIPPINCOTT-RAVEN PUBL
Harjes U, Bridges E, McIntyre A, Fielding BA, Harris AL (2014) Fatty acid-binding protein 4, a point of convergence for angiogenic and metabolic signaling pathways in endothelial cells., J Biol Chem 289 (33) pp. 23168-23176
Fatty acid-binding protein 4 (FABP4) is an adipogenic protein and is implicated in atherosclerosis, insulin resistance, and cancer. In endothelial cells, FABP4 is induced by VEGFA, and inhibition of FABP4 blocks most of the VEGFA effects. We investigated the DLL4-NOTCH-dependent regulation of FABP4 in human umbilical vein endothelial cells by gene/protein expression and interaction analyses following inhibitor treatment and RNA interference. We found that FABP4 is directly induced by NOTCH. Stimulation of NOTCH signaling with human recombinant DLL4 led to FABP4 induction, independently of VEGFA. FABP4 induction by VEGFA was reduced by blockade of DLL4 binding to NOTCH or inhibition of NOTCH signal transduction. Chromatin immunoprecipitation of the NOTCH intracellular domain showed increased binding to two specific regions in the FABP4 promoter. The induction of FABP4 gene expression was dependent on the transcription factor FOXO1, which was essential for basal expression of FABP4, and FABP4 up-regulation following stimulation of the VEGFA and/or the NOTCH pathway. Thus, we show that the DLL4-NOTCH pathway mediates endothelial FABP4 expression. This indicates that induction of the angiogenesis-restricting DLL4-NOTCH can have pro-angiogenic effects via this pathway. It also provides a link between DLL4-NOTCH and FOXO1-mediated regulation of endothelial gene transcription, and it shows that DLL4-NOTCH is a nodal point in the integration of pro-angiogenic and metabolic signaling in endothelial cells. This may be crucial for angiogenesis in the tumor environment.
Fernandez C, Schuhmann K, Herzog R, Fielding B, Frayn K, Shevchenko A, James P, Holm C, Strom K (2011) Altered Desaturation and Elongation of Fatty Acids in Hormone-Sensitive Lipase Null Mice, PLOS ONE 6 (6) ARTN e21603 PUBLIC LIBRARY SCIENCE
Dhar H, Fielding BA, Clark ML, Frayn KN (1990) Background turbidity changes during the estimation of urinary albumin., Ann Clin Biochem 27 ( Pt 2) pp. 161-162
Ardilouze JL, Karpe F, Currie JM, Frayn KN, Fielding BA (2004) Subcutaneous adipose tissue blood flow varies between superior and inferior levels of the anterior abdominal wall, INTERNATIONAL JOURNAL OF OBESITY 28 (2) pp. 228-233 NATURE PUBLISHING GROUP
Tran C, Jacot-Descombes D, Lecoultre V, Fielding BA, Carrel G, Le K-A, Schneiter P, Bortolotti M, Frayn KN, Tappy L (2010) Sex differences in lipid and glucose kinetics after ingestion of an acute oral fructose load, BRITISH JOURNAL OF NUTRITION 104 (8) pp. 1139-1147 CAMBRIDGE UNIV PRESS
Hodson L, Fielding BA (2010) Trafficking and partitioning of fatty acids: the transition from fasted to fed state, CLINICAL LIPIDOLOGY 5 (1) pp. 131-144 FUTURE MEDICINE LTD
Most postprandial studies have investigated the response of a single meal, yet the ingestion of sequential meals is more typical in a Western society. The aim of this review is to explain how natural and stable isotope tracers of fatty acids have been used to investigate the metabolism of dietary fat after single and multiple meals, with a focus on in vivo measurements of adipose tissue metabolism. When stable isotope tracers are combined with arteriovenous difference measurements, very specific measurements of metabolic flux across tissues can be made. We have found that adipose tissue is a net importer of dietary fat for 5 h following a single test meal and for most of the day during a typical three-meal eating pattern. When dietary fat is cleared from plasma, some fatty acids spillover into the plasma and contribute up to 50% of postprandial plasma NEFA concentrations. Therefore, plasma NEFA concentrations after a meal reflect the balance between intracellular and extracellular lipolysis in adipose tissue. This balance is altered after the acute ingestion of fructose. The enzyme lipoprotein lipase is a key modulator of fatty acid flux in adipose tissue and its rate of action is severely diminished in obese men. In conclusion, in vivo studies of human metabolism can quantify the way that adipose tissue fatty acid trafficking modulates plasma lipid concentrations. This has implications for the flux of fatty acids to tissues that are susceptible to ectopic fat deposition such as the liver and muscle. © 2011 The Authors.
Chong MF-F, Hodson L, Bickerton AS, Roberts R, Neville M, Karpe F, Frayn KN, Fielding BA (2008) Parallel activation of de novo lipogenesis and stearoyl-CoA desaturase activity after 3 d of high-carbohydrate feeding, AMERICAN JOURNAL OF CLINICAL NUTRITION 87 (4) pp. 817-823 AMER SOC CLINICAL NUTRITION
PRICE DA, CLOSE GC, FIELDING BA (1984) AGE OF APPEARANCE OF CIRCADIAN-RHYTHM IN SALIVARY CORTISOL-LEVELS, PEDIATRIC RESEARCH 18 (1) pp. 118-118 WILLIAMS & WILKINS
Kotronen A, Seppala-Lindroos A, Vehkavaara S, Bergholm R, Frayn KN, Fielding BA, Yki-Javinen H (2009) Liver fat and lipid oxidation in humans, LIVER INTERNATIONAL 29 (9) pp. 1439-1446 WILEY-BLACKWELL PUBLISHING, INC
Adiels M, Larsson T, Sutton P, Taskinen M-R, Boren J, Fielding BA (2010) Optimization of N-methyl-N-[tert-butyldimethylsilyl]- trifluoroacetamide as a derivatization agent for determining isotopic enrichment of glycerol in very-low density lipoproteins, RAPID COMMUNICATIONS IN MASS SPECTROMETRY 24 (5) pp. 586-592 JOHN WILEY & SONS LTD
Summers LKM, Barnes SC, Fielding BA, Beysen C, Ilic V, Humphreys SM, Frayn KN (2000) Uptake of individual fatty acids into adipose tissue in relation to their presence in the diet, AMERICAN JOURNAL OF CLINICAL NUTRITION 71 (6) pp. 1470-1477 AMER SOC CLINICAL NUTRITION
Pinnick K, Neville M, Clark A, Fielding B (2010) Reversibility of Metabolic and Morphological Changes Associated With Chronic Exposure of Pancreatic Islet beta-Cells to Fatty Acids, JOURNAL OF CELLULAR BIOCHEMISTRY 109 (4) pp. 683-692 WILEY-LISS
Hodson L, Skeaff CM, Fielding BA (2008) Fatty acid composition of adipose tissue and blood in humans and its use as a biomarker of dietary intake, PROGRESS IN LIPID RESEARCH 47 (5) pp. 348-380 PERGAMON-ELSEVIER SCIENCE LTD
Frayn KN, Fielding BA, Karpe F (2005) Adipose tissue fatty acid metabolism and cardiovascular disease, CURRENT OPINION IN LIPIDOLOGY 16 (4) pp. 409-415 LIPPINCOTT WILLIAMS & WILKINS
FIELDING BA, HUMPHREYS SM, SHADID S, FRAYN KN (1995) PLASMA MONOACYLGLYCEROL, DIACYLGLYCEROL AND TRIACYLGLYCEROL MEASUREMENTS IN A STUDY OF FAT UPTAKE BY HUMAN ADIPOSE-TISSUE IN-VIVO, BIOCHEMICAL SOCIETY TRANSACTIONS 23 (3) pp. S487-S487 PORTLAND PRESS
Lord SR, Collins J, Fielding B, Buffa F, Karpe F, Harris A (2011) METFORMIN'S EFFECTS ON BREAST CANCER LIPID METABOLISM, ANNALS OF ONCOLOGY 22 pp. 31-31 OXFORD UNIV PRESS
Fielding BA, Frayn KN (2002) Lipid metabolism, CURRENT OPINION IN LIPIDOLOGY 13 (5) pp. 573-575 LIPPINCOTT WILLIAMS & WILKINS
The expansion of lower-body adipose tissue (AT) is paradoxically associated with reduced cardiovascular disease and diabetes risk. We examined whether the beneficial metabolic properties of lower-body AT are related to the production and release of the insulin-sensitizing lipokine palmitoleate (16:1n-7). Using venoarterial difference sampling, we investigated the relative release of 16:1n-7 from lower-body (gluteofemoral) and upper-body (abdominal subcutaneous) AT depots. Paired gluteofemoral and abdominal subcutaneous AT samples were analyzed for triglyceride fatty acid composition and mRNA expression. Finally, the triglyceride fatty acid composition of isolated human preadipocytes was determined. Relative release of 16:1n-7 was markedly higher from gluteofemoral AT compared with abdominal subcutaneous AT. Stearoyl-CoA desaturase 1 (SCD1), the key enzyme involved in endogenous 16:1n-7 production, was more highly expressed in gluteofemoral AT and was associated with greater enrichment of 16:1n-7. Furthermore, isolated human preadipocytes from gluteofemoral AT displayed a higher content of SCD1-derived fatty acids. We demonstrate that human gluteofemoral AT plays a major role in determining systemic concentrations of the lipokine palmitoleate. Moreover, this appears to be an inherent feature of gluteofemoral AT. We propose that the beneficial metabolic properties of lower-body AT may be partly explained by the intrinsically greater production and release of palmitoleate.
Beysen C, Karpe F, Fielding BA, Clark A, Levy JC, Frayn KN (2002) Interaction between specific fatty acids, GLP-1 and insulin secretion in humans, DIABETOLOGIA 45 (11) pp. 1533-1541 SPRINGER-VERLAG
FIELDING BA, HUMPHREYS SM, ALLMAN RFC, FRAYN KN (1993) MONOACYLGLYCEROL, DIACYLGLYCEROL, AND TRIACYLGLYCEROL CONCENTRATIONS IN HUMAN PLASMA - EFFECTS OF HEPARIN INJECTION AND OF A HIGH-FAT MEAL, CLINICA CHIMICA ACTA 216 (1-2) pp. 167-173 ELSEVIER SCIENCE BV
Fielding BA, Reid G, Grady M, Humphreys SM, Evans K, Frayn KN (2000) Ethanol with a mixed meal increases postprandial triacylglycerol but decreases postprandial non-esterified fatty acid concentrations, BRITISH JOURNAL OF NUTRITION 83 (6) pp. 597-604 C A B INTERNATIONAL
DAVIES AG, PRICE DA, HOULTON CA, BURN JL, FIELDING BA, POSTLETHWAITE RJ (1984) CONTINUOUS SUBCUTANEOUS INSULIN INFUSION IN DIABETES-MELLITUS - A YEARS PROSPECTIVE TRIAL, ARCHIVES OF DISEASE IN CHILDHOOD 59 (11) pp. 1027-1033 BRITISH MED JOURNAL PUBL GROUP
Sibbons C, Boyle L, Burdge GC, Umpleby M, Lilycrop KA, Hartwick CA, Lanham-New S, Hart K, Fielding BA (2015) Evaluation of fatty acid status in children of different nationalities, PROCEEDINGS OF THE NUTRITION SOCIETY 74 (OCE1) pp. E94-E94 CAMBRIDGE UNIV PRESS
Frayn KN, Karpe F, Fielding BA, Macdonald IA, Coppack SW (2003) Integrative physiology of human adipose tissue, INTERNATIONAL JOURNAL OF OBESITY 27 (8) pp. 875-888 NATURE PUBLISHING GROUP
Fielding BA, Samra JS, Ravell CL, Frayn KN (1999) Metabolism of individual fatty acids during infusion of a triacylglycerol emulsion, LIPIDS 34 (6) pp. 535-541 AMER OIL CHEMISTS SOC A O C S PRESS
Roberts R, Bickerton A, Fielding BA, Blaak E, Wagenmakers AJM, Gilbert M, Karpe F, Frayn KN (2004) A new protocol to study fatty acid metabolism in muscle and adipose tissue in subjects with the metabolic syndrome, INTERNATIONAL JOURNAL OF OBESITY 28 pp. S165-S165 NATURE PUBLISHING GROUP
Karmi A, Iozzo P, Viljanen A, Hirvonen J, Fielding BA, Virtanen K, Oikonen V, Kemppainen J, Viljanen T, Guiducci L, Haaparanta-Solin M, Nagren K, Solin O, Nuutila P (2010) Increased Brain Fatty Acid Uptake in Metabolic Syndrome, DIABETES 59 (9) pp. 2171-2177 AMER DIABETES ASSOC
Karpe F, Bickerton A, Fielding B, Hodson L, Ruge T, Frayn K (2007) Abnormalities in fatty acid storage and delivery in the metabolic syndrome, INTERNATIONAL JOURNAL OF OBESITY 31 pp. S6-S6 NATURE PUBLISHING GROUP
Tan GD, Neville MJ, Liverani E, Humphreys SM, Currie JM, Dennis L, Fielding BA, Karpe F (2006) The in vivo effects of the Pro12Ala PPAR gamma 2 polymorphism on adipose tissue NEFA metabolism: the first use of the Oxford Biobank, DIABETOLOGIA 49 (1) pp. 158-168 SPRINGER
Bernini F, Costet P, Ehrenborg E, Fisher R, Fielding B, Freeman D, Groen A, Malle E, Mulder M, Niemeier A, Hansen AT, von Eckardstein A (2012) European Lipoprotein Club: Report of the 34th ELC annual conference, Tutzing, 5-8 September 2011, Atherosclerosis 221 (1) pp. 287-293
Hodson L, Neville M, Chong MFF, Rogers I, Huda SS, Freeman DJ, Frayn KN, Fielding BA (2013) Micro-techniques for analysis of human adipose tissue fatty acid composition in dietary studies, Nutrition, Metabolism and Cardiovascular Diseases 23 (11) pp. 1128-1133
Background and aims: Adipose tissue (AT) fatty acid (FA) composition is considered to be the gold standard long-term biomarker of dietary fatty acid intake. Typically this measurement is made directly from samples collected via large-needle-biopsy or incision. However, with growing interest in the role of AT in relation to health, ideally the fatty acid composition would be analysed along with other measurements, such as gene expression or histology, on a single AT sample. Here we assess alternative ways of obtaining AT for measuring FA composition, in some cases in conjunction with other measurements. Methods and results: The FA composition of tissue obtained via different methods was compared to that of tissue collected via large-needle or surgical biopsy. Fatty acid composition was not significantly different in AT collected by small-needle mini-biopsy (n=10), from an RNA 'lipid layer' (obtained during RNA extraction, 2 sites, n=6 for each), or from cryosectioned tissue prepared for histology (n=10). We also assessed the usefulness of the composition of plasma NEFA as a surrogate marker of subcutaneous AT (n=58-80). Most FAs in plasma NEFA correlated strongly with those in AT (P
Bucci M, Karmi AC, Iozzo P, Badeau RM, Borra R, Saunavaara V, Pham T, Hannukainen JC, Kalliokoski K, Haaparanta-Solin M, Viljanen T, Parkkola R, Nuutila P, Fielding BA, Frayn KN, Viljanen A (2014) Enhanced fatty acid uptake in visceral adipose tissue is not reversed by weight loss in obese individuals with the metabolic syndrome, Diabetologia
Conclusions/interpretation: The data demonstrate that weight loss caused by VLCD does not affect abdominal fasting NEFA uptake rates. We found that visceral fat takes up more NEFAs than subcutaneous AT depots, even after weight loss.
Maldonado EM, Fielding BA, Fisher CP, Moore JB (2015) Quantitative lipid profiling of the early response to either fructose or glucose in an in vitro model of steatosis, PROCEEDINGS OF THE NUTRITION SOCIETY 74 (OCE5) pp. E282-E282 CAMBRIDGE UNIV PRESS
Karmi AC, Viljanen A, Borra R, Fielding B, Viljanen T, Frayn K, Iozzo P, Nuutila P (2009) The effect of weight loss on intra-abdominal fatty acid metabolism in metabolic syndrome, DIABETOLOGIA 52 pp. S75-S75 SPRINGER
FIELDING BA, HOULTON CA, PRICE DA, POSTLETHWAITE RJ (1983) AN ENZYME-LINKED IMMUNOSORBENT-ASSAY FOR THE MEASUREMENT OF URINARY ALBUMIN, EUROPEAN JOURNAL OF PEDIATRICS 140 (2) pp. 207-207 SPRINGER VERLAG
Karpe F, Fielding BA, Ilic V, Humphreys SM, Frayn KN (2002) Monitoring adipose tissue blood flow in man: a comparison between the (133)xenon washout method and microdialysis, INTERNATIONAL JOURNAL OF OBESITY 26 (1) pp. 1-5 NATURE PUBLISHING GROUP
Ardilouze J-L, Sotorník R, Dennis LA, Fielding BA, Frayn KN, Karpe F (2012) Failure to increase postprandial blood flow in subcutaneous adipose tissue is associated with tissue resistance to adrenergic stimulation, Diabetes and Metabolism 38 (1) pp. 27-33
Halliwell KJ, Fielding BA, Samra JS, Humphreys SM, Frayn KN (1996) Release of individual fatty acids from human adipose tissue in vivo after an overnight fast, JOURNAL OF LIPID RESEARCH 37 (9) pp. 1842-1848 LIPID RESEARCH INC
Fielding BA, Humphreys SM, Shadid S, Frayn KN (1995) Arterio-venous differences across human adipose tissue for mono-, di- and triacylglycerols before and after a high-fat meal, Endocrinology and Metabolism 2 (1) pp. 13-17
The purpose of this study was to determine whether or not partial acylglycerols, resulting from triacylglycerol hydrolysis, accumulate during the process of fat deposition in vivo. We measured mono-, di- and triacylglycerol levels in arterialized and adipose tissue venous plasma in normal subjects before and after a test meal. The mean concentrations of partial acylglycerols were consistently low in all plasma samples, accounting for less than 2% of the total acylglycerol measurement. The absence of monoacylglycerol accumulation in the adipose tissue venous plasma samples indicates that the disposal of monoacylglycerol by the adipose tissue was not rate limiting for complete hydrolysis of triacylglycerol in vivo. After heparin was injected intravenously 300 min after the high-fat meal, the mean concentration of monoacylglycerol in arterialized plasma increased from 1.6 ± 0.6 ¼mol/l to 106 ± 19 ¼mol/l (P = 0.01), whereas the mean concentration of diacylglycerol did not change (13.0 ± 2.3 ¼mol/l before, 17.4 ± 4.2 ¼mol/l after).
DHAR H, FIELDING BA, CLARK ML, FRAYN KN (1990) TURBIDITY IN IMMUNOTURBIDIMETRIC ASSAY - REPLY, ANNALS OF CLINICAL BIOCHEMISTRY 27 pp. 509-509 ROYAL SOC MEDICINE SERVICES LTD
Fielding BA, Frayn KN (2003) Lipid metabolism, CURRENT OPINION IN LIPIDOLOGY 14 (4) pp. 389-391 LIPPINCOTT WILLIAMS & WILKINS
Summers LKM, Fielding BA, Ilic V, Clark ML, Frayn KN (1999) The relationship between insulin sensitivity and postprandial adipose tissue lipid metabolism, DIABETOLOGIA 42 pp. A205-A205 SPRINGER VERLAG
Sniderman AD, Cianflone K, Summers L, Fielding B, Frayn K (1997) The acylation-stimulating protein pathway and regulation of postprandial metabolism, PROCEEDINGS OF THE NUTRITION SOCIETY 56 (2) pp. 703-712 C A B INTERNATIONAL
Tan GD, Savage DB, Fielding BA, Collins J, Hodson L, Humphreys SM, O'Rahilly S, Chatterjee K, Frayn KN, Karpe F (2008) Fatty Acid Metabolism in Patients with PPAR gamma Mutations, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 93 (11) pp. 4462-4470 ENDOCRINE SOC
Bickerton AST, Roberts R, Fielding BA, Tornqvist H, Blaak EE, Wagenmakers AJM, Gilbert M, Humphreys SM, Karpe F, Frayn KN (2008) Adipose tissue fatty acid metabolism in insulin-resistant men, DIABETOLOGIA 51 (8) pp. 1466-1474 SPRINGER
Chong MFF, Bickerton A, Roberts R, Karpe F, Hodson L, Fielding B, Frayn K (2006) De novo lipogenesis (DNL) occurs after a 3-day eucaloric low-fat, high-carbohydrate (HC) solid food diet, FASEB JOURNAL 20 (5) pp. A1022-A1023 FEDERATION AMER SOC EXP BIOL
Fielding BA, Humphreys SM, Shadid S, Frayn KN (1995) Plasma mono-, di- and triacylglycerol measurements in a study of fat uptake by human adipose tissue in vivo., Biochem Soc Trans 23 (3)
Irvine NA, Lillycrop KA, Fielding B, Torrens C, Hanson MA, Burdge GC (2015) Polyunsaturated fatty acid biosynthesis is involved in phenylephrine-mediated calcium release in vascular smooth muscle cells, Prostaglandins Leukotrienes and Essential Fatty Acids
© 2015. Stimulation of vascular smooth muscle (VSM) ±1-adrenoceptors induces myosin phosphorylation and vasoconstriction via mobilisation of intracellular calcium and production of specific eicosanoids. Polyunsaturated fatty acid (PUFA) biosynthesis in VSM cells is involved, although the precise mechanism is not known. To address this, we characterised PUFA biosynthesis in VSM cells and determined its role in intracellular calcium release and eicosanoid production. Murine VSM cells converted 18:2n-6 to longer chain PUFA including 22:5n-6. ´6 (D6d) and ´5 (D5d) desaturase, and elongase (Elovl) 5 were expressed. Elovl2 was not detected in human, mouse or rat VSM cells, or in rat or mouse aortae, but tit was not associated with hypermethylation of its promoter. D6d or D5d inhibition reduced 18:3n-6 and 20:4n-6 synthesis, respectively, and induced concentration-related decrease in phenylephrine-mediated calcium release, and in PGE2 and PGF2± secretion. Together these findings suggest that PUFA biosynthesis in VSM cells is involved in calcium release associated with vasoconstriction.
Frayn KN, Coppack SW, Fielding BA, Humphreys SM (1995) Coordinated regulation of hormone-sensitive lipase and lipoprotein lipase in human adipose tissue in vivo: implications for the control of fat storage and fat mobilization., Adv Enzyme Regul 35 pp. 163-178
The enzymes lipoprotein lipase (LPL, EC 184.108.40.206) and hormone-sensitive lipase (HSL, EC 220.127.116.11) apparently catalyze opposing functions in white adipose tissue: the former is concerned with fat storage, the latter with fat mobilization. We have studied their regulation in vivo in normal subjects in the postabsorptive state and after eating meals of different compositions, by measurement of arteriovenous concentration differences for triacylglycerol, non-esterified fatty acids and glycerol across a subcutaneous adipose depot. The two enzymes are regulated in a broadly reciprocal manner: in the overnight-fasted state, HSL is more active, but after a meal HSL is suppressed whilst LPL is activated. The movement of fatty acids in and out of adipose tissue appears to be driven by concentration gradients generated by regulation of these two enzymes, and also by activation, in the postprandial period, of the process of fatty acid esterification. The results show some interesting and perhaps unexpected features of metabolic regulation. Of the fatty acids generated by the action of LPL on circulating TAG, a large proportion is released directly into the venous plasma: close to 100% in the overnight-fasted state, and 50% or more at the peak of LPL action after a meal, making what appear reasonable assumptions. We suggest that this apparent 'inefficiency' of fat storage reflects the energetic cost of maintaining precise control over such a fundamental process. Although LPL is usually thought of as the enzyme regulating fat deposition, in fact the fatty acids and glycerol it releases from circulating TAG represent a substantial proportion of those released from adipose tissue, especially in the postprandial state. In addition, although HSL is considered the enzyme responsible for fat mobilization, suppression of its activity is essential to normal regulation of fat deposition. Thus, fat storage and fat mobilization during normal daily life are controlled by coordinated regulation of a number of enzymatic processes in white adipose tissue.
Fielding BA, Frayn KN (1998) Lipoprotein lipase and the disposition of dietary fatty acids, BRITISH JOURNAL OF NUTRITION 80 (6) pp. 495-502 C A B INTERNATIONAL
Hodson L, McQuaid SE, Karpe F, Frayn KN, Fielding BA (2009) Differences in partitioning of meal fatty acids into blood lipid fractions: a comparison of linoleate, oleate, and palmitate, AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM 296 (1) pp. E64-E71 AMER PHYSIOLOGICAL SOC
Westerbacka J, Kotronen A, Fielding BA, Wahren J, Hodson L, Perttila J, Seppanen-Laakso T, Suortti T, Arola J, Hultcrantz R, Castillo S, Olkkonen VM, Frayn KN, Oresic M, Yki-Jarvinen H (2010) Splanchnic Balance of Free Fatty Acids, Endocannabinoids, and Lipids in Subjects With Nonalcoholic Fatty Liver Disease, GASTROENTEROLOGY 139 (6) pp. 1961-U232 W B SAUNDERS CO-ELSEVIER INC
Banerjee R, Rial BF, Suttie J, Lewandowski A, Robson MD, Schneider J, Hodson L, Fielding B, Collier JD, Barnes E, Neubauer S (2012) WAIST CIRCUMFERENCE GREATER THAN 90CM IS A RISK FACTOR FOR HEPATIC STEATOSIS IN OTHERWISE HEALTHY ADULTS - A 3 TESLA MAGNETIC RESONANCE SPECTROSCOPY STUDY, JOURNAL OF HEPATOLOGY 56 pp. S504-S504
Bickerton A, Roberts R, Fielding B, Blaak E, Wagenmakers AJM, Gilbert M, Karpe F, Frayn KN (2004) Fatty acid oxidation in the metabolic syndrome, ATHEROSCLEROSIS 175 (2) pp. S7-S7 ELSEVIER SCI IRELAND LTD
Tan GD, Fielding BA, Currie JM, Humphreys SM, Desage M, Frayn K, Laville M, Vidal H, Karpe F (2005) The effects of rosiglitazone on fatty acid and triglyceride metabolism in type 2 diabetes, DIABETOLOGIA 48 (1) pp. 83-95 SPRINGER
Moffitt JH, Fielding BA, Evershed R, Berstan R, Currie JM, Clark A (2005) Adverse physicochemical properties of tripalmitin in beta cells lead to morphological changes and lipotoxicity in vitro, DIABETOLOGIA 48 (9) pp. 1819-1829 SPRINGER
Hodson L, Fielding BA (2012) Stearoyl-CoA desaturase: rogue or innocent bystander?, Prog Lipid Res 52 (1) pp. 15-42
Different lipid fractions in humans have characteristic fatty acid profiles and these are maintained partly through diet and to a lesser extent through endogenous synthesis. The enzyme stearoyl-CoA desaturase (SCD; EC 18.104.22.168) is the rate-limiting enzyme in the synthesis of monounsaturated fatty acids such as palmitoleic acid (16:1 n-7) and oleic acid (18:1 n-9). These are the two most abundant monounsaturated fatty acids in human plasma lipids, membranes and adipose tissue. Although in quantitative terms, the endogenous synthesis of fatty acids in humans is not great in most circumstances, it is becoming increasingly evident that SCD plays important structural and metabolic roles. In addition, 16:1 n-7 has been purported to act as a beneficial 'lipokine' in an animal model. Research in humans has relied on indirect measurements of SCD1 activity and therefore, much of our understanding has come from work on animal models. However, results have been somewhat counterintuitive and confusing, so the purpose of this review is to try to summarise our current understanding of this fascinating enzyme.
McQuaid SE, Humphreys SM, Hodson L, Fielding BA, Karpe F, Frayn KN (2010) Femoral Adipose Tissue May Accumulate the Fat That Has Been Recycled as VLDL and Nonesterified Fatty Acids, DIABETES 59 (10) pp. 2465-2473 AMER DIABETES ASSOC
Gutierrez E, Wiggins D, Fielding B, Gould AP (2007) Specialized hepatocyte-like cells regulate Drosophila lipid metabolism, NATURE 445 (7125) pp. 275-280 NATURE PUBLISHING GROUP
Fielding BA, Humphreys SM, Allman RF, Frayn KN (1993) Mono-, di- and triacylglycerol concentrations in human plasma: effects of heparin injection and of a high-fat meal., Clin Chim Acta 216 (1-2) pp. 167-173
A sensitive method has been developed to measure specific mono-, di- and triacylglycerol concentrations in human plasma, using thin-layer chromatography and enzymatic assay. The levels of partial acylglycerols in human plasma from fasting subjects were lower than previous reports had suggested and amounted to less than 3% of the total acylglycerols. After heparin injection the plasma monoacylglycerol concentration increased markedly (P
Robertson MD, Jackson KG, Williams CM, Fielding BA, Frayn KN (2000) Modified sham feeding of a modest-fat meal suppresses plasma non-esterified fatty acids., PROCEEDINGS OF THE NUTRITION SOCIETY 59 pp. 123A-123A C A B INTERNATIONAL
Jackson KG, Robertson MD, Fielding BA, Frayn KN, Williams CM (2001) Second meal effect: modified sham feeding does not provoke the release of stored triacylglycerol from a previous high-fat meal, BRITISH JOURNAL OF NUTRITION 85 (2) pp. 149-156 C A B INTERNATIONAL
Hodson L, Fielding BA, Bickerton A, Roberts R, Milne RW, Frayn KN, Karpe E (2005) Incorporation of exogenous and endogenous fatty acids into very low-density lipoprotein (VLDL): a study using stable isotope and immunoaffinity techniques in humans, DIABETOLOGIA 48 pp. A233-A233 SPRINGER
Summers LKM, Fielding BA, Ilic V, Quinlan PT, Frayn KN (1998) The effect of triacylglycerol fatty acid positional distribution on postprandial metabolism in subcutaneous adipose tissue, BRITISH JOURNAL OF NUTRITION 79 (2) pp. 141-147 C A B INTERNATIONAL
Riserus U, Tan GD, Fielding BA, Neville MJ, Currie J, Savage DB, Chatterjee VK, Frayn KN, O'Rahilly S, Karpe F (2005) Rosiglitazone increases indexes of stearoyl-CoA desaturase activity in humans - Link to insulin sensitization and the role of dominant-negative mutation in peroxisome proliferator-activated receptor-gamma, DIABETES 54 (5) pp. 1379-1384 AMER DIABETES ASSOC
FIELDING BA, PRICE DA, HOULTON CA (1983) ENZYME-IMMUNOASSAY FOR URINARY ALBUMIN, CLINICAL CHEMISTRY 29 (2) pp. 355-357 AMER ASSOC CLINICAL CHEMISTRY
Robertson MD, Jackson KG, Fielding BA, Williams CM, Frayn KN (2002) Acute effects of meal fatty acid composition on insulin sensitivity in healthy post-menopausal women., Br J Nutr 88 (6) pp. 635-640
Postprandial plasma insulin concentrations after a single high-fat meal may be modified by the presence of specific fatty acids although the effects of sequential meal ingestion are unknown. The aim of the present study was to examine the effects of altering the fatty acid composition in a single mixed fat-carbohydrate meal on glucose metabolism and insulin sensitivity of a second meal eaten 5 h later. Insulin sensitivity was assessed using a minimal model approach. Ten healthy post-menopausal women underwent four two-meal studies in random order. A high-fat breakfast (40 g fat) where the fatty acid composition was predominantly saturated fatty acids (SFA), n-6 polyunsaturated fatty acids (PUFA), long-chain n-3 PUFA or monounsaturated fatty acids (MUFA) was followed 5 h later by a low-fat, high-carbohydrate lunch (5.7 g fat), which was identical in all four studies. The plasma insulin response was significantly higher following the SFA meal than the other meals after both breakfast and lunch (P
Karpe F, Fielding BA, Ilic V, Macdonald IA, Summers LKM, Frayn KN (2002) Impaired postprandial adipose tissue blood flow response is related to aspects of insulin sensitivity, DIABETES 51 (8) pp. 2467-2473 AMER DIABETES ASSOC
Ardilouze J-L, Sotorník R, Dennis LA, Fielding BA, Frayn KN, Karpe F (2011) Failure to increase postprandial blood flow in subcutaneous adipose tissue is associated with tissue resistance to adrenergic stimulation, Diabetes and Metabolism
Marinou K, Hodson L, Frayn KN, Karpe F, Fielding BA (2007) Sources of fatty acids for 3-hydroxybutyrate production differ during short-term fasting in men and women, ATHEROSCLEROSIS SUPPLEMENTS 8 (1) pp. 23-24 ELSEVIER IRELAND LTD
Fielding BA, Humphreys SM, Frayn KN (1993) Mono- and di-acylglycerol concentrations in human plasma in relation to lipoprotein lipase activity., Biochem Soc Trans 21 ( Pt 3) (3)
Robertson MD, Jackson KG, Williams CM, Fielding BA, Frayn KN (2001) Prolonged effects of modified sham feeding on energy substrate mobilization, AMERICAN JOURNAL OF CLINICAL NUTRITION 73 (1) pp. 111-117 AMER SOC CLINICAL NUTRITION
Evans K, Kuusela PJ, Cruz ML, Wilhelmova I, Fielding BA, Frayn KN (1998) Rapid chylomicron appearance following sequential meals: effects of second meal composition, BRITISH JOURNAL OF NUTRITION 79 (5) pp. 425-429 C A B INTERNATIONAL
Bucci M, Karmi AC, Iozzo P, Fielding BA, Viljanen A, Badeau RM, Borra R, Saunavaara V, Pham T, Hannukainen JC, Kalliokoski K, Haaparanta-Solin M, Viljanen T, Parkkola R, Frayn KN, Nuutila P (2014) Enhanced fatty acid uptake in visceral adipose tissue is not reversed by weight loss in obese individuals with the metabolic syndrome, Diabetologia 58 (1) pp. 158-164
© 2014, Springer-Verlag Berlin Heidelberg.Methods: NEFA uptake in AT depots was measured with [18F]-fluoro-6-thia-heptadecanoic acid (18F-FTHA) and positron emission tomography (PET) in 18 obese participants with the metabolic syndrome before and after a 6 week VLCD. Whole body fat oxidation was measured using indirect calorimetry and [U-13C]palmitate. Sixteen non-obese participants were controls.Results: Obese participants had >100% higher (p
Moffitt JH, Fielding B, Currie J, Clark A (2004) Triacylglycerol formed in islet beta cells exposed to fatty acids do not contribute to decreased viability except in cells forming predominantly tripalmitin, DIABETOLOGIA 47 pp. A176-A176 SPRINGER
Hodson L, Harnden K, Banerjee R, Real B, Marinou K, Karpe F, Fielding BA (2014) Lower resting and total energy expenditure in postmenopausal compared with premenopausal women matched for abdominal obesity., J Nutr Sci 3
The menopause is accompanied by increased risk of obesity, altered body fat distribution and decreased skeletal muscle mass. The resulting decrease in RMR should be accompanied by a compensatory change in energy balance to avoid weight gain. We aimed to investigate habitual energy intake and expenditure in pre- and postmenopausal women matched for abdominal obesity. We recruited fifty-one healthy Caucasian women, BMI > 18·5 and
Costet P, Ehrenborg E, Fisher R, Fielding B, Groen A, Kardassis D, Malle E, Mulder M, Niemeier A, Norata GD, Hansen AT, Eckardstein AV (2012) European Lipoprotein Club: Report of the 35th ELC Annual Conference (Tutzing, 10th-13th September 2012), Atherosclerosis
Chong MF-F, Fielding BA, Frayn KN (2007) Mechanisms for the acute effect of fructose on postprandial lipemia, AMERICAN JOURNAL OF CLINICAL NUTRITION 85 (6) pp. 1511-1520 AMER SOC CLINICAL NUTRITION
Sell H, Blueher M, Kloeting N, Schlich R, Willems M, Ruppe F, Knoefel WT, Dietrich A, Fielding BA, Arner P, Frayn KN, Eckel J (2013) Adipose Dipeptidyl Peptidase-4 and Obesity Correlation with insulin resistance and depot-specific release from adipose tissue in vivo and in vitro, DIABETES CARE 36 (12) pp. 4083-4090
AMER DIABETES ASSOC
Nydahl MC, Smith RD, Kelly CNM, Fielding BA, Williams CM (2003) Achievement of dietary fatty acid intakes in long-term controlled intervention studies: approach and methodology, PUBLIC HEALTH NUTRITION 6 (1) pp. 31-40 C A B I PUBLISHING
Hodson L, Ruge T, Milne R, Fielding BA, Frayn KN, Karpe F (2006) Dietary fat is a major contributor to VLDL production in the fed state in humans, ATHEROSCLEROSIS 188 (1) pp. S3-S4 ELSEVIER IRELAND LTD
Lundbom J, Hakkarainen A, Fielding B, Soderlund S, Westerbacka J, Taskinen M-R, Lundbom N (2010) Characterizing human adipose tissue lipids by long echo time H-1-MRS in vivo at 1.5 Tesla: validation by gas chromatography, NMR IN BIOMEDICINE 23 (5) pp. 466-472 WILEY-BLACKWELL
Hodson L, Banerjee R, Rial B, Arlt W, Adiels M, Boren J, Marinou K, Fisher C, Mostad IL, Stratton IM, Barrett PHR, Chan DC, Watts GF, Harnden K, Karpe F, Fielding BA (2015) Menopausal Status and Abdominal Obesity Are Significant Determinants of Hepatic Lipid Metabolism in Women, JOURNAL OF THE AMERICAN HEART ASSOCIATION 4 (10) ARTN e002258 WILEY-BLACKWELL
Fielding BA, Callow J, Owen RM, Samra JS, Matthews DR, Frayn KN (1996) Postprandial lipemia: The origin of an early peak studied by specific dietary fatty acid intake during sequential meals, AMERICAN JOURNAL OF CLINICAL NUTRITION 63 (1) pp. 36-41 AMER SOC CLIN NUTRITION INC
Phillips DIW, Caddy S, Ilic V, Fielding BA, Frayn KN, Borthwick AC, Taylor R (1996) Intramuscular triglyceride and muscle insulin sensitivity: Evidence for a relationship in nondiabetic subjects, METABOLISM-CLINICAL AND EXPERIMENTAL 45 (8) pp. 947-950 W B SAUNDERS CO
McQuaid SE, Hodson L, Neville MJ, Dennis AL, Cheeseman J, Humphreys SM, Ruge T, Gilbert M, Fielding BA, Frayn KN, Karpe F (2011) Downregulation of Adipose Tissue Fatty Acid Trafficking in Obesity A Driver for Ectopic Fat Deposition?, DIABETES 60 (1) pp. 47-55 AMER DIABETES ASSOC
Karpe F, Bickerton AS, Hodson L, Fielding BA, Tan GD, Frayn KN (2007) Removal of triacylglycerols from chylomicrons and VLDL by capillary beds: the basis of lipoprotein remnant formation, BIOCHEMICAL SOCIETY TRANSACTIONS 35 pp. 472-476 PORTLAND PRESS LTD
Griffin BA, Fielding BA (2001) Postprandial lipid handling, CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE 4 (2) pp. 93-98 LIPPINCOTT WILLIAMS & WILKINS
Pinnick KE, Collins SC, Londos C, Gauguier D, Clark A, Fielding BA (2008) Pancreatic ectopic fat is characterized by adipocyte infiltration and altered lipid composition, OBESITY 16 (3) pp. 522-530 NATURE PUBLISHING GROUP
Summers LKM, Fielding BA, Bradshaw HA, Ilic V, Beysen C, Clark ML, Moore NR, Frayn KN (2002) Substituting dietary saturated fat with polyunsaturated fat changes abdominal fat distribution and improves insulin sensitivity, DIABETOLOGIA 45 (3) pp. 369-377 SPRINGER-VERLAG
Frayn KN, Fielding BA, Macdonald IA, Coppack SW, Lawrence V, Karpe F (2004) Pulsatile blood flow and lipolysis in human adipose tissue, INTERNATIONAL JOURNAL OF OBESITY 28 pp. S81-S81 NATURE PUBLISHING GROUP
Kalant D, Phelis S, Fielding BA, Frayn KN, Cianflone K, Sniderman AD (2000) Increased postprandial fatty acid trapping in subcutaneous adipose tissue in obese women, JOURNAL OF LIPID RESEARCH 41 (12) pp. 1963-1968 LIPID RESEARCH INC
Loh NY, Neville MJ, Marinou K, Hardcastle SA, Fielding BA, Duncan EL, McCarthy MI, Tobias JH, Gregson CL, Karpe F, Christodoulides C (2015) LRP5 regulates human body fat distribution by modulating adipose progenitor biology in a dose- and depot-specific fashion., Cell Metab 21 (2) pp. 262-272
Common variants in WNT pathway genes have been associated with bone mass and fat distribution, the latter predicting diabetes and cardiovascular disease risk. Rare mutations in the WNT co-receptors LRP5 and LRP6 are similarly associated with bone and cardiometabolic disorders. We investigated the role of LRP5 in human adipose tissue. Subjects with gain-of-function LRP5 mutations and high bone mass had enhanced lower-body fat accumulation. Reciprocally, a low bone mineral density-associated common LRP5 allele correlated with increased abdominal adiposity. Ex vivo LRP5 expression was higher in abdominal versus gluteal adipocyte progenitors. Equivalent knockdown of LRP5 in both progenitor types dose-dependently impaired ²-catenin signaling and led to distinct biological outcomes: diminished gluteal and enhanced abdominal adipogenesis. These data highlight how depot differences in WNT/²-catenin pathway activity modulate human fat distribution via effects on adipocyte progenitor biology. They also identify LRP5 as a potential pharmacologic target for the treatment of cardiometabolic disorders.
Umpleby M, Shojaee-Moradie F, Fielding B, Li X, Isherwood C, Jackson N, Wilinska G, Hovorka R, Bell J, Thomas EL, Wright J, Frost GS, Griffin B (2015) A DIET LOW IN SUGAR REDUCES THE PRODUCTION OF ATHEROGENIC LIPOPROTEINS IN MEN WITH HIGH LIVER FAT, ATHEROSCLEROSIS 241 (1) pp. E46-E46 ELSEVIER IRELAND LTD
Theytaz F, Noguchi Y, Egli L, Campos V, Buehler T, Hodson L, Patterson BW, Nishikata N, Kreis R, Mittendorfer B, Fielding B, Boesch C, Tappy L (2012) Effects of supplementation with essential amino acids on intrahepatic lipid concentrations during fructose overfeeding in humans, American Journal of Clinical Nutrition 96 (5) pp. 1008-1016
Background: A high dietary protein intake has been shown to blunt the deposition of intrahepatic lipids in high-fat- and high-carbohydrate-fed rodents and humans. Objective: The aim of this study was to evaluate the effect of essential amino acid supplementation on the increase in hepatic fat content induced by a high-fructose diet in healthy subjects. Design: Nine healthy male volunteers were studied on 3 occasions in a randomized, crossover design after 6 d of dietary intervention. Dietary conditions consisted of a weight-maintenance balanced diet (control) or the same balanced diet supplemented with 3 g fructose·kg-1·d-1and 6.77 g of a mixture of 5 essential amino acids 3 times/d (leucine, isoleucine, valine, lysine, and threonine) (HFrAA) or with 3 g fructose·kg-1·d -1 and a maltodextrin placebo 3 times/d (HFr); there was a washout period of 4 to 10 wk between each condition. For each condition, the intrahepatocellular lipid (IHCL) concentration, VLDL-triglyceride concentration, and VLDL-[13C]palmitate production were measured after oral loading with [13C]fructose. Results: HFr increased the IHCL content (1.27 ± 0.31 compared with 2.74 ± 0.55 vol %; P
Summers LKM, Fielding BA, Ilic V, Frayn KN (1998) The relationship between body mass index, abdominal fat distribution, insulin sensitivity and plasma lipids, DIABETOLOGIA 41 pp. A347-A347 SPRINGER VERLAG
There is net outward flow of fatty acids from adipose tissue in the fasted state but net inward flow and storage in the postprandial state. We investigated how this is regulated. Arteriovenous differences were measured across a subcutaneous adipose depot in six normal subjects before and for 5 h after a meal containing 80 g fat and 80 g carbohydrate. In five further experiments, insulin was infused at 40 mU.m-2.min-1 from 30 min after the meal, clamping the plasma glucose. Net transcapillary fatty acid flow changed from negative (outward flow from tissue to capillaries) in the postabsorptive state to consistently positive (net inward flow, implying fat storage) after the meal despite continued net efflux of fatty acids into venous blood. In the "clamped" experiments (with additional insulin), net fatty acid efflux in the venous blood was suppressed and positive transcapillary flux (storage) was more marked. Regulation of fatty acid flow appeared to depend on coordinated changes in hormone-sensitive lipase (HSL) and lipoprotein lipase (LPL) action and fatty acid esterification. Additional insulin caused no further suppression of HSL or activation of LPL but markedly stimulated fatty acid retention (presumed to represent esterification). In the absence of additional insulin, a high proportion of the fatty acids liberated by LPL are released into the venous plasma in both postabsorptive and postprandial states. We hypothesize that this "loss" of fatty acids is necessary to give precise control to the pathway of fat storage.
Riserus U, Sprecher D, Jonson T, Olson E, Hirschberg S, Fang Z, Hegde P, Richards D, Sarov-Blat L, Strum J, Cheeseman J, Fielding B, Moore N, Murgatroyd P, O'Rahilly S, Sutton P, Willson T, Hassall D, Keith F, Karpe F (2007) PPAR-delta activation reverses multiple metabolic abnormalities, reduces oxidative stress and promotes fat oxidation in obese humans, INTERNATIONAL JOURNAL OF OBESITY 31 (9) pp. 1487-1487 NATURE PUBLISHING GROUP
Bickerton AST, Roberts R, Fielding BA, Hodson L, Blaak EE, Wagenmakers AJM, Gilbert M, Karpe F, Frayn KN (2007) Preferential uptake of dietary fatty acids in adipose tissue and muscle in the postprandial period, DIABETES 56 (1) pp. 168-176 AMER DIABETES ASSOC
Marinou K, Hodson L, Vasan SK, Fielding BA, Banerjee R, Brismar K, Koutsilieris M, Clark A, Neville MJ, Karpe F (2014) Structural and functional properties of deep abdominal subcutaneous adipose tissue explain its association with insulin resistance and cardiovascular risk in men, Diabetes Care 37 (3) pp. 821-829
OBJECTIVE Fat distribution is an important variable explaining metabolic heterogeneity of obesity. Abdominal subcutaneous adipose tissue (SAT) is divided by the Scarpa's fascia into a deep subcutaneous adipose tissue (dSAT) and a superficial subcutaneous adipose tissue (sSAT) layer. This study sought to characterize functional differences between the two SAT layers to explore their relative contribution to metabolic traits and cardiovascular risk (CVR) profile. RESEARCH DESIGN AND METHODS We recruited 371 Caucasians consecutively from a local random, populationbased screening project in Oxford and 25 Asian Indians fromthe local community. The depth of the SAT layers was determined by ultrasound (US), and adipose tissue (AT) biopsies were performed under US guidance in a subgroup of 43 Caucasians. Visceral adipose tissue (VAT) mass was quantified by dual-energy X-ray absorptiometry scan. RESULTS Male adiposity in both ethnic groups was characterized by a disproportionate expansion of dSAT, which was strongly correlated with VAT mass. dSAT depth was a strong predictor of global insulin resistance (IR; homeostatic model assessment of IR), liver-specific IR (insulin-like growth factor binding protein-1), and Framingham risk score independently of other measures of adiposity in men. Moreover, dSAT had higher expression of proinflammatory, lipogenic, and lipolytic genes and contained higher proportions of saturated fatty acids. There was increased proportion of small adipocytes in dSAT. CONCLUSIONS SAT is heterogeneous; dSAT expands disproportionally more than sSAT with increasing obesity in Caucasian males (confirmed also in Asian Indians). Its expansion is related to increased CVR independent of other adiposity measures, and it has biological properties suggestive of higher metabolic activity contributing to global IR.© 2014 by the American Diabetes Association.
Iozzo P, Bucci M, Roivainen A, Nagren K, Jaervisalo MJ, Kiss J, Guiducci L, Fielding B, Naum AG, Borra R, Virtanen K, Savunen T, Salvadori PA, Ferrannini E, Knuuti J, Nuutila P (2010) Fatty Acid Metabolism in the Liver, Measured by Positron Emission Tomography, Is Increased in Obese Individuals, GASTROENTEROLOGY 139 (3) pp. 846-U203 W B SAUNDERS CO-ELSEVIER INC
Karpe F, Fielding BA, Coppack SW, Lawrence VJ, Macdonald IA, Frayn KN (2005) Oscillations of fatty acid and glycerol release from human subcutaneous adipose tissue in vivo, DIABETES 54 (5) pp. 1297-1303 AMER DIABETES ASSOC
Purpose of review
In 2004, the ?omega-3 index? was described as the sum of eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3) in red blood cells (RBCs) as an index of coronary heart disease mortality. This review outlines new evidence to support the omega-3 index as a tool to inform disease prognosis.
Recent studies have reported differential metabolism of EPA and DHA. High dose supplementation with EPA and DHA led to increased levels of RBC DHA that were associated with decreased liver fat. EPA and DHA in RBCs were associated with reduced mortality in a prospective study of patients with cardiac disease; the strongest association was with EPA. A diet containing 9.5 g alpha linolenic acid lead to an increase in EPA but not DHA status in middle aged women.
Dietary intake or supplementation studies with n-3 fatty acids should include measurement of n-3 status in a standardised way. The omega-3 index, reflecting EPA and DHA status throughout the body, is convenient and may be appropriate in some cases, but since EPA and DHA assimilate differently in membranes, and have different potency, measurement of individual fatty acid composition in RBCs may be more informative
Food security can be improved by reducing post-harvest losses in sustainable food product chains. About 50% of fish is lost during filleting, including significant levels of high quality protein (10?23% (w/w)), which may be a source for biofunctional peptides. The fish processing waste protein hydrolysate can be a potential solution for minimizing the environmental issues related to marine processing products, and act as an alternative to producing value added fish processing by products. The main aim of this study was to investigate the physicochemical properties of fish processing waste streams from Atlantic Mackerel (Scomber scombrus) and mixed fish by membrane separation.
Protein hydrolysates of Atlantic Mackerel (Scomber scombrus) and mixed fish from fish waste streams were prepared by enzymatic hydrolysis using pepsin and pancreatin and measured for their antioxidant and functional properties. The chemical composition (moisture, protein, total lipids and ash) of the Atlantic mackerel and Nile Perch (Lates niloticus) fish fillets (FF) compared to fish waste (FW) was also investigated.
Protein fractions from the fish waste samples were separated by using the TFF cogent ¼scale ultrafiltration system from Millipore, and parameters including transmembrane pressure (TMP) on flux excursion, protein performance scalability, mass transfer analysis, as well as hold up volume were studied. The mechanism of antioxidant activity was studied by DPPH, FRAP, FTC and TBARS assays. It was demonstrated that fish waste water protein hydrolysate especially for Atlantic Mackerel showed good antioxidant activities by the Ferric Thiocyanate (FTC) and Thiobarbituric acid Reactive substances (TBARS) methods and compared well with other antioxidants (BHA, ascorbic acid and trolox). There was significant difference (p
Structural and thermodynamic changes in fish waste samples were also determined by FT-Raman spectroscopy, differential scanning calorimetry (DSC) and small deformation rheology respectively. The DSC thermograms from the samples indicated that fish waste samples may be comparable. Moreover in fish waste sample hydrolysates, the same trends were obtained in 10 kDa AM and MF fractions. Fish waste samples especially hydrolysed fish waste samples, showed different protein denaturation transition peaks, indicating that enzymatic hydrolysis can affect the thermodynamic and functional properties of protein samples. Similarly, the rheological properties were different for different fish samples (AM and MF) with AM showing higher G? or elastic modulus values (p
Abstract: Dietary fructose has been linked to an increased post-prandial triglyceride (TG) level, which is an established independent risk factor for cardiovascular disease. Although much research has focused on the effects of fructose consumption on liver-derived very-low density lipoprotein (VLDL), emerging evidence also suggests that fructose may raise post-prandial TG levels by affecting the metabolism of enterocytes of the small intestine. Enterocytes have become well recognised for their ability to transiently store lipids following a meal and to thus control post-prandial TG levels according to the rate of chylomicron (CM) lipoprotein synthesis and secretion. The influence of fructose consumption on several aspects of enterocyte lipid metabolism are discussed, including de novo lipogenesis, apolipoprotein B48 and CM-TG production, based on the findings of animal and human isotopic tracer studies. Methodological issues affecting the interpretation of fructose studies conducted to date are highlighted, including the accurate separation of CM and VLDL. Although the available evidence to date is limited, disruption of enterocyte lipid metabolism may make a meaningful contribution to the hypertriglyceridaemia often associated with fructose consumption.
Specialized metabolic-sensors in the hypothalamus regulate blood glucose levels by influencing hepatic glucose output and hypoglycemic counter regulatory responses. Hypothalamic reactive oxygen species (ROS) may act as a metabolic signal mediating responses to changes in glucose, other substrates and hormones. The role of ROS in the brain?s control of glucose homeostasis remains unclear. We hypothesized that hydrogen peroxide (H2O2), a relatively stable form of ROS, acts as a sensor of neuronal glucose consumption and availability and that lowering brain H2O2 with the enzyme catalase would lead to systemic responses increasing blood glucose. During hyperinsulinemic euglycemic clamps in rats, ICV catalase infusion resulted in increased hepatic glucose output, which was associated with reduced neuronal activity in the arcuate nucleus of the hypothalamus (ARC). Electrophysiological recordings revealed a subset of ARC neurons expressing pro-opiomelanocortin (POMC) that were inhibited by catalase and excited by H2O2. During hypoglycemic clamps, ICV catalase increased glucagon and epinephrine responses to hypoglycemia, consistent with perceived lower glucose levels. Our data suggest that H2O2 represents an important metabolic cue which, through tuning the electrical activity of key neuronal populations such as POMC neurons, may have a role in the brain?s influence of glucose homeostasis and energy balance.
Umpleby Margot, Shojaee-Moradie F, Fielding Barbara, Li X, Marino A, Alsini N, Isherwood Cheryl, Jackson N, Ahmad A, Stolinski M, Lovegrove JA, Johnsen Sigurd, Mendis Agampodi, Wright John, Wilinska ME, Hovorka R, Bell JD, Thomas EL, Frost GS, Griffin Bruce (2017) Impact of liver fat on the differential partitioning of hepatic triacylglycerol into VLDL subclasses on high and low sugar diets, Clinical Science 131 (21) pp. 2561-2573
Dietary sugars are linked to the development of non-alcoholic fatty liver disease (NAFLD)
and dyslipidaemia, but it is unknown if NAFLD itself influences the effects of sugars on
plasma lipoproteins. To study this further, men with NAFLD (n=11) and low liver fat
?controls? (n= 14) were fed two iso-energetic diets, high or low in sugars (26% or 6% total
energy) for 12 weeks, in a randomised, cross-over design. Fasting plasma lipid and
lipoprotein kinetics were measured after each diet by stable isotope trace-labelling.
There were significant differences in the production and catabolic rates of VLDL subclasses
between men with NAFLD and controls, in response to the high and low sugar diets. Men
with NAFLD had higher plasma concentrations of VLDL1-triacylglycerol (TAG) after the
rate after the high sugar diet (P
low sugar diet (P
hepatic TAG into a higher production of VLDL1-TAG (P
contrast, a higher production of VLDL2-TAG (P
VLDL subclass kinetics could be explained, in part, by differences in the contribution of
fatty acids from intra-hepatic stores, and de novo lipogenesis. This study provides new
evidence that liver fat accumulation leads to a differential partitioning of hepatic TAG into
large and small VLDL subclasses, in response to high and low intakes of sugars.
Polyunsaturated fatty acids (PUFAs) are important for immune function. Limited evidence
indicates that immune cell activation involves endogenous PUFA synthesis, but this has not
been characterised. To address this, we measured metabolism of 18:3n-3 in quiescent and
activated peripheral blood mononuclear cells (PBMCs), and in Jurkat T cell leukaemia.
PBMCs from men and women (n = 34) were incubated with [1-13C]18:3n-3 with or without
Concanavalin A (Con. A). 18:3n-3 conversion was undetectable in unstimulated PBMCs, but
up-regulated when stimulated. The main products were 20:3n-3 and 20:4n-3, while 18:4n-3
was undetectable, suggesting initial elongation and D8 desaturation. PUFA synthesis was
17.4-fold greater in Jurkat cells than PBMCs. The major products of 18:3n-3 conversion in
Jurkat cells were 20:4n-3, 20:5n-3 and 22:5n-3. 13C Enrichment of 18:4n-3 and 20:3n-3
suggests parallel initial elongation and 6 desaturation. The FADS2 inhibitor SC26196
reduced PBMC, but not Jurkat cell, proliferation suggesting PUFA synthesis is involved in
regulating mitosis in PBMCs. Con. A stimulation increased FADS2, FADS1, ELOVL5 and
ELOVL4 mRNA expression in PBMCs. A single transcript corresponding to the major
isoform of FADS2, FADS20001, was detected in PBMCs and Jurkat cells. PBMC activation
induced hypermethylation of a 470bp region in the FADS2 5?-regulatory sequence. This
region was hypomethylated in Jurkat cells compared to quiescent PBMCs. These findings
show that PUFA synthesis involving initial elongation and D8 desaturation is involved in
regulating PBMC proliferation and is regulated via transcription possibly by altered DNA
methylation. These processes were dysregulated in Jurkat cells. This has implications for
understanding the regulation of mitosis in normal and transformed lymphocytes.
Conversion of the essential n-3 (18:3n-3) and n-6 (18:2n-6) fatty acids to longer chain polyunsaturated fatty acids (PUFA) involves sequential desaturation and elongation reactions. Previous studies have reported gender differences in n-3 PUFA synthesis, whereas the effect of age is less clear. n-3 PUFAs are reported to have important effects on immune cell function. A previous study reported long chain PUFA synthesis in mitogen stimulated but not quiescent peripheral blood mononuclear cells (PBMCs). However, the underlying mechanism is not known.
PUFA synthesis was investigated in PBMCs incubated with [1-13C]18:3n-3 for 48 h. Activation with the T-lymphocyte mitogen concanavalin A (Con A) increased PUFA synthesis. 22:6n-3 synthesis was not detected. [1-13C] incorporation was greatest for 20:3n-3 suggesting initial chain elongation is an important fate for 18:3n-3. Con A increased expression of three key genes (FADS2, FADS1 and ELOVL5) involved in PUFA synthesis, suggesting upregulation of the pathway is controlled at the transcriptional level. ELOVL2 expression was negligible, possibly explaining the lack of 22:6n-3 synthesis. Con A increased methylation of 12 CpGs in the FADS2 promoter contradicting the general view that DNA methylation represses transcription. Subsequent 5?RACE analysis verified that activated PBMCs were not using an alternative promoter for FADS2 transcription. Contrary to expectation, 18:3n-3 conversion in activated PBMCs was not affected by gender or menopausal status and there was no clear age effect.
PUFA synthesis was constitutive in the Jurkat T-lymphocyte leukaemic cell-line and was higher than in PBMCs. FADS2, FADS1 and ELOVL5 mRNA expression was also higher in Jurkat cells and was associated with 50% lower methylation of 17 CpGs in the FADS2 promoter, suggesting transcriptional dysregulation of PUFA synthesis in Jurkat cells involves altered DNA methylation.
These findings have provided novel insights into the regulation of PUFA biosynthesis in PBMCs and upregulation of the pathway in activated PBMCs suggests that newly synthesised PUFAs may be important for cell function.
Objectives: To comprehensively survey the sugar and
nutrient contents of yogurt products available in UK
supermarkets, in particular those marketed to children.
Design: A cross-sectional survey of yogurt products
available in the UK?s supermarkets in November 2016.
Methods: Data were collected from five major online
UK supermarkets and a process flow strategy was used
to place yogurts into eight categories: children?s, dairy
alternatives, dessert, drinks, fruit, flavoured, natural/Greek
style and organic. A comprehensive database of product
information for 921 unique products was created and
Results: The total sugar, fat, protein, calcium and energy
contents were highly variable across categories, and
the ranges were extremely broad. Although lower than
the dessert category, the medians (range) of the total
sugar content of children?s (10.8 g/100 g (4.8?14.5)),
fruit (11.9 g/100 g (4.6?21.3)), flavoured (12.0 g/100 g
(0.1?18.8)) and organic (13.1 g/100 g (3.8?16.9)) yogurt
products were all well above 10 g/100 g, and represented
>45% of total energy. Only two out of 101 children?s
yogurt and fromage frais products surveyed qualified
as low sugar (d5 g/100 g). Natural/Greek yogurts had
dramatically lower sugar contents (5.0 g/100 g (1.6, 9.5),
largely lactose) than all other categories. While low-fat
higher fat yogurts, nonetheless 55% (285 of 518 low-fat
yogurts) contained between 10 and 20 g sugar/100 g.
Within the children?s category, fromage frais had higher
protein (5.3 g/100 g (3.3, 8.6) vs 3.2 (2.8, 7.1); p
and calcium contents (150 mg/100 g (90, 240) vs
130.5 mg/100 g (114, 258); p=0.0015) than yogurts.
Conclusions: While there is good evidence that yogurt
can be beneficial to health, products on the market vary
widely in total sugars. Fewer than 9%, and only 2% of
the children?s, products surveyed were low enough in
sugar to earn ?green? in UK front of the pack labelling.
Reformulation for the reduction of free sugars in yogurts is
GLP-1 agonists control postprandial glucose and lipid excursion in type 2 diabetes; however the mechanism(s) are unclear.
To determine the mechanism(s) of postprandial lipid and glucose control with lixisenatide (GLP-1 analogue) in type 2 diabetes.
Randomised, double-blind, cross-over study.
Centre for Diabetes, Endocrinology, and Research, Royal Surrey County Hospital, Guildford, UK
Eight obese men with type 2 diabetes (57.3±1.9yrs; BMI 30.3±1.0kg/m2, HbA1C 66.5±2.6mmol/mol, [8.2±0.3%]).
Two metabolic studies, four-weeks after lixisenatide or placebo; with cross-over and repetition of studies.
Main outcome measures
Study one: very-low density lipoprotein (VLDL) and chylomicron (CM) triacylglycerol (TAG) kinetics were measured with iv bolus of [2H5]glycerol in a 12h study, with hourly feeding. Oral [13C]triolein, in a single meal, labelled enterally-derived TAG.
Study two: glucose kinetics were measured with [U-13C]glucose in a mixed-meal (plus acetaminophen to measure gastric emptying) and variable iv [6,6-2H2]glucose infusion.
Study one: CM-TAG (but not VLDL-TAG) pool-size, was lower with lixisenatide (P=0.046). Lixisenatide reduced CM [13C]oleate AUC60-480min concentration (P=0.048) and increased CM-TAG clearance; with no effect on CM-TAG production rate.
Study two: postprandial glucose and insulin AUC0-240min were reduced with lixisenatide (P=0.0051, PÂ0.05). Total glucose production rate (Ra) (P=0.015), Rameal (P=0.0098) and acetaminophen AUC0-360min (P=0.006) were lower with lixisenatide than placebo.
Lixisenatide reduced [13C]oleate concentration, derived from a single meal in CM-TAG, as well as glucose Rameal, through delayed gastric emptying. However day-long CM production, measured with repeated meal-feeding, was not reduced by lixisenatide and decreased CM-TAG concentration was due to increased CM-TAG clearance.
Background: Observational studies often infer hepatic de novo lipogenesis (DNL) by measuring circulating fatty acid (FA) markers; however it remains to be elucidated whether these markers accurately reflect hepatic DNL.
Objective: We investigated associations between fasting hepatic DNL and proposed FA markers of DNL in subjects consuming their habitual diet.
Design: Fasting hepatic DNL was assessed using ²H2O (heavy water) in 149 non-diabetic men and women and measuring the synthesis of very low-density lipoprotein triglyceride (VLDL-TG) palmitate. FA markers of blood lipid fractions was determined by gas chromatography (GC).
Results: Neither the lipogenic index (16:0/18:2n-6) nor the SCD index (16:1n-7/16:0) in VLDL-TG were associated with isotopically assessed DNL (r=0.13, P=0.1 and r=-0.08, P=0.35, respectively). The relative abundance (mol%) of 14:0, 16:0 and 18:0 in VLDL-TG were weakly (rd0.35) associated with DNL whereas abundance of 16:1n-7, 18:1n-7 and 18:1n-9 were not associated. When the cohort was split by median DNL, only abundance of 14:0 and 18:0 in VLDL-TG could discriminate between subjects having high (11.5%) and low (3.8%) fasting hepatic DNL. Based on a subgroup, FA markers in total plasma TG, plasma cholesteryl esters, plasma phospholipids and red blood cell phospholipids were generally not associated with DNL.
Conclusions: The usefulness of circulating FAs as markers of hepatic DNL in healthy individuals consuming their habitual diet is limited due to their inability to clearly discriminate between individuals with low and high fasting hepatic DNL.
Morigny Pauline, Houssier Marianne, Mairal Aline, Ghilain Claire, Etienne Mouisel, Benhamed Fadila, Masri Bernard, Recazens Emeline, Denechaud Pierre-Damien, Tavernier Geneviève, Caspar-Bauguil Sylvie, Virtue Sam, Sramkova Veronika, Monbrun Laurent, Mazars Anne, Zazoun Madjid, Guilmeau Sandra, Barquissau Valentin, Beuzelin Diane, Bonnel Sophie, Marques Marie, Monge-Roffarello Boris, Lefort Corinne, Fielding Barbara, Sulpice Thierry, Astrup Arne, Payrastre Bernard, Bertrand-Michel Justine, Meugnier Emmanuelle, Ligat Laetitia, Lopez Frederic, Guillou Hervé, Ling Charlotte, Holm Cecilia, Rabasa-Lhoret Remi, Saris Wim, Stich Vladimir, Arner Peter, Ryden Mikael, Moro Cedric, Viguerie Nathalie, Harms Matthew, Hallén Stefan, Vidal-Puig Antonio, Vidal Hubert, Postic Catherine, Langin Dominique (2018) Interaction between Hormone-Sensitive Lipase and ChREBP in Fat Cells Controls Insulin Sensitivity, Nature Metabolism
Impaired adipose tissue insulin signalling is a critical feature of insulin resistance. Here we identify a pathway linking the lipolytic enzyme hormone-sensitive lipase (HSL) to insulin action via the glucose-responsive transcription factor ChREBP and its target, the fatty acid elongase ELOVL6. Genetic inhibition of HSL in human adipocytes and mouse adipose tissue results in enhanced insulin sensitivity and induction of ELOVL6. ELOVL6 promotes an increase in phospholipid oleic acid, which modifies plasma membrane fluidity and enhances insulin signalling. HSL deficiency?mediated effects are suppressed by gene silencing of ChREBP and ELOVL6. Mechanistically, physical interaction between HSL, independent of lipase activity, and the isoform activated by glucose metabolism ChREBP± impairs ChREBP± translocation into the nucleus and induction of ChREBP², the isoform with high transcriptional activity that is strongly associated with whole-body insulin sensitivity. Targeting the HSL?ChREBP interaction may allow therapeutic strategies for the restoration of insulin sensitivity.
Potatoes have been an affordable, staple part of the diet for many hundreds of years. Recently however, there has been a decline in consumption, perhaps influenced by erroneous reports of being an unhealthy food. This review provides an overview of the nutritional value of potatoes and examines the evidence for associations between potato consumption and non-communicable diseases. Potatoes are an important source of micronutrients, such as vitamin C, vitamin B6, potassium, folate, and iron and contribute a significant amount of fibre to the diet. However, nutrient content is affected by cooking method; boiling causes leaching of water-soluble nutrients, whereas frying can increase the resistant starch content of the cooked potato. Epidemiological studies have reported associations between potato intake and obesity, type 2 diabetes and cardiovascular disease. However, results are contradictory and confounded by lack of detail on cooking methods. Indeed, potatoes have been reported to be more satiating than other starchy carbohydrates, such as pasta and rice, which may aid weight maintenance. Future research should consider cooking methods in the study design in order to reduce confounding factors and further explore the health impact of this food.
Background: Cardiovascular disease (CVD) remains a significant cause of mortality globally, with a reduction in free sugars consumption a public health target for decreasing disease burden. Fructose raises post-prandial triacylglycerol (TAG) concentrations (risk factor for CVD), relative to glucose or sucrose, possibly due disrupted intestinal TAG metabolism.
Aims: Determine whether effects of high-fructose consumption on plasma TAG concentration are explained by intestinal and/or hepatic TAG lipoprotein kinetics, as well as de novo lipogenesis (DNL), in humans and an in vitro model.
Methods: Five overweight males consumed drinks containing 30% energy as fructose or complex carbohydrate hourly for 11h on two separate occasions, in a randomised cross-over design (4 week washout). Stable isotopes were given to measure DNL, chylomicron (CM)-TAG and VLDL-TAG kinetics. CM and VLDL were separated according to their apolipoprotein B (apoB) content (Sf>20 fraction). Caco-2 cells were treated (96h) with different fructose and glucose concentrations, or a mixture of sugars (?Mix?), and stable isotopes tracers ([13C6]-fructose; [13C6]-glucose). TAG enrichments were measured by gas chromatography-mass spectrometry.
Results: Fructose consumption in comparison to the complex CHO had no effect on either intestinal or hepatic DNL. Intestinal and hepatic DNL were correlated in the fasted (P
Conclusions: Fructose increased post-prandial TAG concentrations, possibly due to less insulin-mediated lipoprotein metabolism. DNL was unaffected by fructose consumption. This study supports public strategies to restrict dietary free sugars.
Fish skin, a by-product of filleting could be upgraded to value-added products for human consumption, thereby preventing waste and pollution. The aims were to prepare gelatin from skin of Nile or black tilapia (Oreochromis nilotica); characterize its physical-chemical, rheological and thermal properties and those of fish gelatin-whey protein mixtures; prepare hydrolysates and assess their foaming properties in the presence and absence of whey protein and green tea.
Gelatin extracted successfully from tilapia skins, gave a 19-26% yield and comprised high protein (90.2 + 0.68 %) and low fat (0.62 + 0.03 %), moisture (5.2 + 0.62 %) and ash content (0.08 + 0.05 %). Amino acid profile included mainly glycine (33.94%), alanine (26.1%) and glutamic acid, proline, arginine, aspartic acid and imino acids. The Bloom strength of 6.67% (w/v) tilapia gelatin in distilled water was higher (301 + 11.6 g) than commercial tilapia (207 + 5.6 g), bovine (~ 225 g), and porcine (~ 300 g) gelatins.
The rheological properties of 3,5 and 10% (w/v) tilapia gelatin indicated G? (elastic modulus) values 1,135 and 720 Pa, respectively, and gelling points of 16.2°C, 5% 17.2°C and 19.8°C respectively whereas melting temperatures were 14.9°C, 14.9°C and 15.0°C respectively. The gels were highly stable over a frequency range of 0-100 rad/sec.
DSC results indicated high melting temperatures (Tm) 22oC, compared to bovine (26.2°C) and porcine (30.7°C) gelatin. Cold water fish gelatin did not gel. However, bovine and porcine gelatins had lower enthalpy change (?H) values 0.58 J/g and 0.45 J/g respectively, compared with tilapia gelatin (2.51 J/g), probably due to protein denaturation of collagen.
In tilapia gelatin-whey protein mixed gels, whey proteins were dominant. Gelling temperatures of 10% WPI with 5% gelatin (88.9°C) or 10% gelatin (87.4°C) mixtures were higher than for WPI (80.3°C) or gelatin at 3% (16.2°C), 5% (17.2°C) and 10% (19.8°C). Whey protein (10%) was unstable but formed a good stable gel network with gelatin at 5 % (597 Pa) and 10% (26974 Pa). Whey (10 %) and gelatin (10%) also gave a strong gel by large deformation analysis. Tm and ?H for 10% whey protein and 5 or 10% gelatin/ mixtures were higher (67.2°C, 68.8°C and 68.2°C respectively) than for gelatin or whey protein alone. The ?H values of gelatins increased when combined with the WPI. Three % gelatin (0.03 J/g), 10% WPI + 3% gelatin (0.44 J/g), 5 % gelatin (0.18 J/g), 10% WPI + 5% gelatin (0.56), 10% gelatin (1.3 J/g) and 10% WPI + 10% gelatin (0.59). Phase contrast microscopy of gelatin showed a fine uniform and homogeneous network with small particles whereas the whey protein structure had larger aggregates. The gelatin-whey mixtures formed a compatible network.
Gelatin produced the highest volume of foam FE (933%), followed by gelatin + whey protein (853%), gelatin hydrolysate + whey protein (767%); these were not significantly different (p>0.05). This was followed by a mixture of gelatin + whey protein + green tea (575%) that was significantly lower (p
mpaired regulation of immune function characterised by chronic inflammation together with a declining protective immune response is a major challenge to healthy ageing. It is therefore important to understand the mechanisms that regulate immune function and the impact of ageing upon such processes. Appropriate induction and resolution of the immune response requires adequate availability of polyunsaturated fatty acids (PUFAs) for incorporation into cell membranes. However, humans are unable to synthesise PUFAs de novo and are dependent upon dietary intake for pre-formed PUFAs or synthesis by the liver from the essential fatty acids, linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (aLNA, 18:3n-3). We have shown that activation of peripheral blood mononuclear cells (PBMCs) 37 increases PUFA biosynthesis from essential fatty acids via a mechanism that involves altered epigenetic regulation of a key gene in the pathway. Moreover, induction of PUFA synthesis is directly involved in the regulation of lymphocyte activation and proliferation. The aim of the BBSRC responsive mode award ?How does polyunsaturated fatty acid biosynthesis regulate T lymphocyte function?? is to determine how PUFA biosynthesis regulates T cell function and the effect of ageing on this process. The project will identify points of regulation in the biosynthetic pathway and how these might influence the capacity for up-regulation of PUFA synthesis in older individuals. We will use stable isotope tracers of LA and aLNA to determine whether newly synthesised PUFAs are preferential substrates for synthesis of lipid mediators and whether they are involved in formation of membrane microdomains that mediate cell signalling.
Lord Simon R., Collins Jennifer M., Cheng Wei-Chen, Haider Syed, Wigfield Simon, Gaude Edoardo, Fielding Barbara A., Pinnick Katherine E., Harjes Ulrike, Segaran Ashvina, Jha Pooja, Hoefler Gerald, Pollak Michael N., Thompson Alastair M., Roy Pankaj G., English Ruth, Adams Rosie F. Adams, Frezza Christian, Buffa Francesca M., Karpe Fredrik, Harris Adrian L. (2019) Transcriptomic analysis of human primary breast cancer identifies fatty acid oxidation as a target for metformin, British Journal of Cancer
Background: Epidemiological studies suggest that metformin may reduce the incidence of cancer in
patients with diabetes and multiple late phase clinical trials assessing the potential of repurposing
this drug are underway. Transcriptomic profiling of tumour samples is an excellent tool to
understand drug bioactivity, identify candidate biomarkers and assess for mechanisms of resistance
Methods: 36 patients with untreated primary breast cancer were recruited to a window study and
transcriptomic profiling of tumour samples carried out before and after metformin treatment.
Results: Multiple genes that regulate fatty acid oxidation were upregulated at the transcriptomic
level and there was a differential change in expression between 2 previously identified cohorts of
patients with distinct metabolic responses. Increase in expression of a mitochondrial fatty oxidation
gene composite signature correlated with change in a proliferation gene signature. In vitro assays
showed that, in contrast to previous studies in models of normal cells, metformin reduces fatty acid
oxidation with a subsequent accumulation of intracellular triglyceride, independent of AMPK
Conclusions: We propose that metformin at clinical doses targets fatty acid oxidation in cancer cells
with implications for patient selection and drug combinations.
Lord Simon R., Collins Jennifer M., Cheng Wei-Chen, Haider Syed, Wigfield Simon, Gaude Edoardo, Fielding Barbara, Pinnick Katherine E., Harjes Ulrike, Segaran Ashvina, Jha Pooja, Hoefler Gerald, Pollak Michael N., Thompson Alastair M., Roy Pankaj G., English Ruth., Adams Rosie F., Frezza Christian, Buffa Francesca M., Karpe Fredrik, Harris Adrian L. (2020) Transcriptomic analysis of human primary breast cancer identifies fatty acid oxidation as a target for metformin, British Journal of Cancer 122 (2) pp. 258-265
Epidemiological studies suggest that metformin may reduce the incidence of cancer in patients with diabetes and multiple late phase clinical trials assessing the potential of repurposing this drug are underway. Transcriptomic profiling of tumour samples is an excellent tool to understand drug bioactivity, identify candidate biomarkers and assess for mechanisms of resistance to therapy.
Thirty-six patients with untreated primary breast cancer were recruited to a window study and transcriptomic profiling of tumour samples carried out before and after metformin treatment.
Multiple genes that regulate fatty acid oxidation were upregulated at the transcriptomic level and there was a differential change in expression between two previously identified cohorts of patients with distinct metabolic responses. Increase in expression of a mitochondrial fatty oxidation gene composite signature correlated with change in a proliferation gene signature. In vitro assays showed that, in contrast to previous studies in models of normal cells, metformin reduces fatty acid oxidation with a subsequent accumulation of intracellular triglyceride, independent of AMPK activation.
We propose that metformin at clinical doses targets fatty acid oxidation in cancer cells with implications for patient selection and drug combinations.
Clinical Trial Registration
We hypothesised that probiotic supplementation (PRO) increases the absorption and oxidation of
orally ingested maltodextrin during 2h endurance cycling, thereby sparing muscle glycogen for a
subsequent time trial (simulating a road race). Measurements were made of lipid and carbohydrate
oxidation, plasma metabolites and insulin, gastrointestinal permeability, and subjective symptoms of
discomfort. Seven male cyclists were randomized to PRO (bacterial composition given in methods) or
placebo (PLC) for four weeks, separated by a 14-day washout period. After each period, cyclists
consumed a 10% maltodextrin solution (initial 8 mL·kg-1 bolus and 2 mL·kg-1 every 15 min) while
exercising for 2h at 55% Wmax followed by a 100 kJ time trial. PRO resulted in small increases in peak
oxidation rates of the ingested maltodextrin (0.84 ± 0.10 vs 0.77 ± 0.09 g·min-1, P = 0.016), and mean
total carbohydrate oxidation (2.20 ± 0.25 vs 1.87 ± 0.39 g·min-1, P = 0.038), while fat oxidation was
reduced (0.40 ± 0.11 vs 0.55 ± 0.10 g·min-1, P = 0.021) . During PRO small but significant increases were
seen in glucose absorption, plasma glucose and insulin concentration and decreases in NEFA and
glycerol. Differences between markers of GI damage and permeability and time trial performance
were not significant (P > 0.05). In contrast to the hypothesis, PRO led to minimal increases in
absorption and oxidation of the ingested maltodextrin and small reductions in fat oxidation, while
having no effect on subsequent time trial performance.
Mycobacterium tuberculosis (Mtb) infects macrophages and macrophage-derived foam cells, a hallmark of granulomata in tuberculous lesions. We analysed the effects of lipid accumulation in human primary macrophages and quantified strong triglyceride and phospholipid remodelling which depended on the dietary fatty acid used for the assay. The enrichment of >70% in triglyceride and phospholipids can alter cell membrane properties, signalling and phagocytosis in macrophages. In conventional macrophage cultures, cells are heterogeneous, small or large macrophages. In foam cells, a third population of 30% of cells with increased granularity can be detected. We found that foam cell formation is heterogenous and that lipid accumulation and foam cell formation reduces the phagocytosis of Mtb. Under the conditions tested, cell death was highly prevalent in macrophages, whereas foam cells were largely protected from this effect. Foam cells also supported slower Mtb replication, yet this had no discernible impact on the intracellular efficacy of four different antitubercular drugs. Foam cell formation had a significant impact in the inflammatory potential of the cells. TNF-±, IL-1² and prototypical chemokines were increased. The ratio of inflammatory IL-1², TNF-± and IL-6 versus anti-inflammatory IL-10 was significantly higher in response to Mtb versus LPS, and was increased in foam cells compared to macrophages, suggestive of increased pro-inflammatory properties. Cytokine production correlated with NF-ºB activation in our models. We conclude that foam cell formation reduces the host cell avidity for, and phagocytosis of, Mtb while protecting the cells from death. This protective effect is associated with enhanced inflammatory potential of foam cells and restricted intracellular growth of Mtb.
Herring Roselle A., Shojaee-Moradie Fariba, Garesse Robert, Stevenage Mary, Jackson Nicola, Fielding Barbara, Mendis Agampodi, Johnsen Sigurd, Umpleby Margot, Davies Melanie, Russell-Jones David L. (2020) Full Title Metabolic effects of an SGLT2 inhibitor (dapagliflozin) during a period of acute insulin withdrawal and development of ketoacidosis in people with type 1 diabetes., Diabetes Care
American Diabetes Association
Objective: To determine the effect of SGLT2 inhibitor dapagliflozin on glucose flux, lipolysis and ketone body concentrations during insulin withdrawal in people with type 1 diabetes.
Research Design and Methods: A double-blind placebo controlled crossover study with a 4-week wash out period was performed in 12 people with type 1 diabetes using insulin pump therapy. Participants received dapagliflozin or placebo in random order for 7 days. Stable isotopes were infused to measure the rate of glucose production (Ra), disappearance (Rd) and lipolysis. At isotopic steady state insulin was withdrawn and the study terminated after 600 minutes or earlier if blood glucose reached 18mmol/L, bicarbonate 5.0 mmol/L.
Results: At baseline, glucose Ra was significantly higher with dapagliflozin than placebo. Following insulin withdrawal, plasma glucose concentrations at the end point were significantly lower with dapagliflozin than placebo and AUC0-180min glucose Rd and AUC0-180min ²-hydroxybutyrate (BOHB) were significantly higher. There was a small but significantly higher AUC0-180min glycerol Ra (measure of lipolysis) with dapagliflozin. Non-esterified fatty acid concentrations were not different between treatments.When divided by BMI>27 and
Conclusions: During insulin withdrawal the increase in BOHB with
dapaglifozin may be partially due to increased lipolysis. However reduced renal excretion, reduced BOHB uptake by peripheral tissues or a metabolic switch to increase ketogenesis within the liver may also play a role.
A high fructose intake exacerbates postprandial plasma triacylglycerol (TAG) concentration, an independent risk factor for cardiovascular disease, although it is unclear whether this is due to increased production or impaired clearance of triacylglycerol (TAG)-rich lipoproteins. We determined the in vivo acute effect of fructose on postprandial intestinal and hepatic lipoprotein TAG kinetics and de novo lipogenesis (DNL). Five overweight men were studied twice, 4 weeks apart. They consumed hourly mixed-nutrient drinks that were high-fructose (30% energy) or low-fructose (