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Turning over our fat stores: the key to metabolic health Blaxter Award Lecture 2018

  • Keith N. Frayn (a1)


The present paper results from my receiving the Nutrition Society's first Blaxter Award, and describes briefly my academic history. My interest in human fat metabolism began in the Medical Research Council's Trauma Unit, studying metabolic changes in critically ill patients and their responses to nutrition. On moving to Oxford in 1986, I began to study pathways for depositing fat in adipose tissue. This involved the development of new methodologies, in particular, a technique for measurement of arterio-venous differences of metabolite concentrations across human adipose tissue beds, primarily the subcutaneous anterior abdominal depot. Our early studies showed that this tissue is dynamic in its metabolic behaviour, responding rapidly (within minutes) to changes in nutritional state. This led to an understanding of adipose tissue as playing an essential role in metabolic health, by capturing incoming dietary fatty acids, storing them as TAG and releasing them when needed, analogous to the role of the liver in glucose metabolism; we called this ‘buffering’ of fatty acid fluxes. In obesity, the mass of adipose tissue expands considerably, more than is often appreciated from BMI values. We confirmed other observations of a strong suppression of release of NEFA from adipose tissue in obesity, tending to normalise circulating NEFA concentrations. A corollary, however, is that fatty acid uptake must be equally suppressed, and this disrupts the ‘buffering’ capacity of adipose tissue, leading to fat deposition in other tissues; ectopic fat deposition. This, in turn, is associated with many metabolic abnormalities linked to obesity.


Corresponding author

Corresponding author: Keith N. Frayn, email


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1.King, RFGJ, Almond, DJ, Oxby, CB et al. (1984) Calculation of short-term changes in body fat from measurement of respiratory gas exchange. Metabolism 33, 826832.
2.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. Progr Lipid Res 47, 348380.
3.Rodbell, M (1964) Metabolism of isolated fat cells. 1. Effects of hormones on glucose metabolism and lipolysis. J Biol Chem 239, 375380.
4.Samra, JS, Frayn, KN, Giddings, JA et al. (1995) Modification and validation of a commercially available portable detector for measurement of adipose tissue blood flow. Clin Physiol 15, 241248.
5.Frayn, KN (2002) Adipose tissue as a buffer for daily lipid flux. Diabetologia 45, 12011210.
6.Spalding, KL, Arner, E, Westermark, PO et al. (2008) Dynamics of fat cell turnover in humans. Nature 453, 783787.
7.Arner, P, Bernard, S, Salehpour, M et al. (2011) Dynamics of human adipose lipid turnover in health and metabolic disease. Nature 478, 110113.
8.Global BMI Mortality Collaboration (2016) Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet 388, 776786.
9.Emerging Risk Factors Collaboration, Wormser, D, Kaptoge, S et al. (2011) Separate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease: collaborative analysis of 58 prospective studies. Lancet 377, 10851095.
10.Cusi, K (2010) The role of adipose tissue and lipotoxicity in the pathogenesis of type 2 diabetes. Curr Diab Rep 10, 306315.
11.Garg, A (2011) Lipodystrophies: genetic and acquired body fat disorders. J Clin Endocrinol Metab 96, 33133325.
12.Tan, GD, Neville, MJ, Liverani, E et al. (2006) The in vivo effects of the Pro12Ala PPARγ2 polymorphism on adipose tissue NEFA metabolism: the first use of the Oxford Biobank. Diabetologia 49, 158168.
13.Karpe, F, Dickmann, JR & Frayn, KN (2011) Fatty acids, obesity, and insulin resistance: time for a reevaluation. Diabetes 60, 24412449.
14.Opie, LH & Walfish, PG (1963) Plasma free fatty acid concentrations in obesity. New Engl J Med 268, 757760.
15.Reeds, DN, Stuart, CA, Perez, O et al. (2006) Adipose tissue, hepatic, and skeletal muscle insulin sensitivity in extremely obese subjects with acanthosis nigricans. Metabolism 55, 16581663.
16.Langin, D, Dicker, A, Tavernier, G et al. (2005) Adipocyte lipases and defect of lipolysis in human obesity. Diabetes 54, 31903197.
17.Jocken, JWE, Langin, D, Smit, E et al. (2007) Adipose triglyceride lipase and hormone-sensitive lipase protein expression is decreased in the obese insulin-resistant state. J Clin Endocrinol Metab 92, 22922299.
18.Summers, LKM, Samra, JS, Humphreys, SM et al. (1996) Subcutaneous abdominal adipose tissue blood flow: variation within and between subjects and relationship to obesity. Clin Sci 91, 679683.
19.Simonsen, L, Bülow, J, Astrup, A et al. (1990) Diet-induced changes in subcutaneous adipose tissue blood flow in man: effect of ß-adrenoceptor inhibition. Acta Physiol Scand 139, 341346.
20.Ardilouze, J, Fielding, B, Currie, J et al. (2004) Nitric oxide and beta-adrenergic stimulation are major regulators of pre- and postprandial subcutaneous adipose tissue blood flow in humans. Circulation 109, 4752.
21.Green, S, O'Connor, E, Kiely, C et al. (2018) Effect of obesity on oxygen uptake and cardiovascular dynamics during whole-body and leg exercise in adult males and females. Physiol Rep 6, e13705.
22.Potts, JL, Coppack, SW, Fisher, RM et al. (1995) Impaired postprandial clearance of triacylglycerol-rich lipoproteins in adipose tissue in obese subjects. Am J Physiol 268, E588EE94.
23.McQuaid, SE, Hodson, L, Neville, MJ et al. (2011) Down-regulation of adipose tissue fatty acid trafficking in obesity: a driver for ectopic fat deposition? Diabetes 60, 4755.
24.Griffin, BA & Fielding, BA (2001) Postprandial lipid handling. Curr Opin Clin Nutr Metab Care 4, 9398.
25.Frayn, KN (2005) Obesity and metabolic disease: is adipose tissue the culprit? Proc Nutr Soc 64, 713.
26.Frayn, KN, Coppack, SW, Humphreys, SM et al. (1989) Metabolic characteristics of human adipose tissue in vivo. Clin Sci 76, 509516.
27.Karpe, F, Fielding, BA, Coppack, SW et al. (2005) Oscillations of fatty acid and glycerol release from human subcutaneous adipose tissue in vivo. Diabetes 54, 12971303.
28.Frayn, KN, Shadid, S, Hamlani, R et al. (1994) Regulation of fatty acid movement in human adipose tissue in the postabsorptive-to-postprandial transition. Am J Physiol 266, E308E317.
29.Ruge, T, Hodson, L, Cheeseman, J et al. (2009) Fasted to fed trafficking of fatty acids in human adipose tissue reveals a novel regulatory step for enhanced fat storage. J Clin Endocrinol Metab 94, 17811788.


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Turning over our fat stores: the key to metabolic health Blaxter Award Lecture 2018

  • Keith N. Frayn (a1)


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