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DOI: 10.1055/s-0030-1269851
© Georg Thieme Verlag KG Stuttgart · New York
Insulin Resistance in the Control of Body Fat Distribution: A New Hypothesis
Publication History
received 21.07.2010
accepted 11.11.2010
Publication Date:
30 November 2010 (online)
Abstract
Obesity causes insulin resistance, which is a prime etiological factor for type 2 diabetes, dyslipidemia, and cardiovascular disease. However, insulin resistance may be a normal physiological response to obesity that limits further fat deposition and which only has pathological effects at high levels. The current hypothesis suggests that in obesity the initial deposition of triglycerides occurs in subcutaneous adipose tissue and as this increases in size insulin resistance will rise and limit further subcutaneous lipid accumulation. Triglycerides will then be diverted to the visceral fat depot as well as to ectopic sites. This leads to a substantial rise in insulin resistance and the prevalence of its associated disorders. Evidence supporting this hypothesis includes studies showing that in lean subjects the prime determinant of insulin resistance is BMI, that is, subcutaneous fat whilst in overweight and obese subjects it is waist circumference and visceral adiposity. It has also been shown that the metabolic syndrome suddenly increases in prevalence at high levels of insulin resistance and we suggest that this is due to the diversion of lipids from the subcutaneous to the visceral depot. This system may have functioned in our evolutionary past to limit excessive adiposity by causing lipid deposition to occur at a site that has maximal effects on insulin resistance but involves minimal weight gain.
Key words
insulin resistance - human adipose tissue - waist circumference - obesity
References
- 1 Eckel RH. Insulin resistance: an adaptation for weight maintenance. Lancet. 1992; 340 1452-1453
- 2 Swinburn BA, Nyomba BL, Saad MF, Zurlo F, Raz I, Knowler WC, Lillioja S, Bogardus C, Ravussin E. Insulin resistance associated with lower rates of weight gain in Pima Indians. J Clin Invest. 1991; 88 168-173
- 3 Ravussin E, Smith SR. Increased fat intake, impaired fat oxidation, and failure of fat cell proliferation result in ectopic fat storage, insulin resistance, and type 2 diabetes mellitus. Ann NY Acad Sci. 2002; 967 363-378
- 4 Frayn KN. Visceral fat and insulin resistance – causative or correlative?. Br J Nutr. 2000; 83 (S 01) S71-S77
- 5 Després JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature. 2006; 444 881-887
- 6 Sniderman AD, Bhopal R, Prabhakaran D, Sarrafzadegan N, Tchernof A. Why might South Asians be so susceptible to central obesity and its atherogenic consequences? The adipose tissue overflow hypothesis. Int J Epidemiol. 2007; 36 220-225
- 7 Bolinder J, Kager L, Ostman J, Arner P. Differences at the receptor and postreceptor levels between human omental and subcutaneous adipose tissue in the action of insulin on lipolysis. Diabetes. 1983; 32 117-123
- 8 Zierath JR, Livingston JN, Thörne A, Bolinder J, Reynisdottir S, Lönnqvist F, Arner P. Regional difference in insulin inhibition of non-esterified fatty acid release from human adipocytes: relation to insulin receptor phosphorylation and intracellular signalling through the insulin receptor substrate-1 pathway. Diabetologia. 1998; 41 1343-1354
- 9 Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004; 89 2548-2556
- 10 Hamdy O, Porramatikul S, Al-Ozairi E. Metabolic obesity: the paradox between visceral and subcutaneous fat. Curr Diabetes Rev. 2006; 2 367-373
- 11 Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS, Klein S, Coppack SW. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab. 1997; 82 4196-4200
- 12 Sopasakis VR, Sandqvist M, Gustafson B Hammarstedt A, Schmelz M, Yang X, Jansson PA, Smith U. High local concentrations and effects on differentiation implicate interleukin-6 as a paracrine regulator. Obes Res. 2004; 12 454-460
- 13 Lefebvre AM, Laville M, Vega N, Riou JP, van Gaal L, Auwerx J, Vidal H. Depot-specific differences in adipose tissue gene expression in lean and obese subjects. Diabetes. 1998; 47 98-103
- 14 Ramis JM, Bibiloni B, Moreiro J, García-Sanz JM, Salinas R, Proenza AM, Lladó I. Tissue leptin and plasma insulin are associated with lipoprotein lipase activity in severely obese patients. J Nutr Biochem. 2005; 16 279-285
- 15 Berndt J, Kralisch S, Klöting N, Ruschke K, Kern M, Fasshauer M, Schön MR, Stumvoll M, Blüher M. Adipose triglyceride lipase gene expression in human visceral obesity. Exp Clin Endocrinol Diabetes. 2008; 116 203-210
- 16 Pouliot MC, Després JP, Nadeau A, Moorjani S, Prud’Homme D, Lupien PJ, Tremblay A, Bouchard C. Visceral obesity in men. Associations with glucose tolerance, plasma insulin, and lipoprotein levels. Diabetes. 1992; 41 826-834
- 17 Katzmarzyk PT, Perusse L, Bouchard C. Genetics of abdominal visceral fat levels. Am J Hum Biol. 1999; 11 225-235
- 18 Rice T, Chagnon YC, Perusse L, Borecki IB, Ukkola O, Rankinen T, Gagnon J, Leon AS, Skinner JS, Wilmore JH, Bouchard C, Rao DC. A genomewide linkage scan for abdominal subcutaneous and visceral fat in black and white families: the HERITAGE Family Study. Diabetes. 2002; 51 848-855
- 19 Seidell JC, Oosterlee A, Deurenberg P, Hautvast JG, Ruijs JH. Abdominal fat depots measured with computed tomography: effects of degree of obesity, sex, and age. Eur J Clin Nutr. 1988; 42 805-815
- 20 Pouliot M-C, Després J-P, Lemieux S, Moorjani S, Bouchard C, Tremblay A, Nadeau A, Lupien PJ. Waist circumference and abdominal sagittal diameter: best simple anthropometric indexes of abdominal visceral adipose tissue accumulation and related cardiovascular risk in men and women. Am J Cardiol. 1994; 73 460-468
- 21 Bonora E, Del Prato S, Bonadonna RC, Gulli G, Solini A, Shank ML, Ghiatas AA, Lancaster JL, Kilcoyne RF, Alyassin AM. Total body fat content and fat topography are associated differently with in vivo glucose metabolism in non-obese and obese non-diabetic women. Diabetes. 1992; 41 1151-1159
- 22 Abate N, Garg A, Peshock RM, Stray-Gundersen J, Grundy SM. Relationships of generalized and regional adiposity to insulin sensitivity in men. J Clin Invest. 1995; 96 88-98
- 23 Goodpaster BH, Thaete EL, Simoneau JA, Kelley DE. Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat. Diabetes. 1997; 46 1579-1585
- 24 Kelley DE, Thaete FL, Troost F, Huwe T, Goodpaster BH. Subdivisions of subcutaneous abdominal adipose tissue and insulin resistance. Am J Physiol Endocrinol Metab. 2000; 278 E941-E948
- 25 Ross R, Aru J, Freeman J, Hudson R, Janssen I. Abdominal adiposity and insulin resistance in obese men. Am J Physiol Endocrinol Metab. 2002; 282 E657-E663
- 26 Ross R, Freeman J, Hudson R, Janssen I. Abdominal obesity, muscle composition, and insulin resistance in premenopausal women. J Clin Endocrinol Metab. 2002; 87 5044-5051
- 27 Ribeiro-Filho FF, Faria AN, Kohlmann NE, Zanella MT, Ferreira SR. Two-hour insulin determination improves the ability of abdominal fat measurement to identify risk for the metabolic syndrome. Diabetes Care. 2003; 26 1725-1730
- 28 Frederiksen L, Nielsen TL, Wraae K, Hagen C, Frystyk J, Flyvbjerg A, Brixen K, Andersen M. Subcutaneous rather than visceral adipose tissue is associated with adiponectin levels and insulin resistance in young men. J Clin Endocrinol Metab. 2009; 94 4010-4015
- 29 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. . Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001; 285 2486-2497
- 30 Park S-H, Lee W-Y, Rhee E-J, Jeon WK, Kim BI, Ryu SH, Kim SW. Relative risks of the metabolic syndrome according to the degree of insulin resistance in apparently healthy Korean adults. Clin Sci. 2005; 108 553-559
- 31 Naran N, Chetty N, Crowther N. The relationship between insulin resistance and individual components of the metabolic syndrome in the South African Indian population. Diabet Med. 2006; 23 (S 04) 742-743
- 32 Lemieux S, Prud’homme D, Nadeau A, Tremblay A, Bouchard C, Després JP. Seven-year changes in body fat and visceral adipose tissue in women. Association with indexes of plasma glucose-insulin homeostasis. Diabetes Care. 1996; 19 983-991
- 33 Zamboni M, Armellini F, Turcato E, Todisco P, Gallagher D, Dalle Grave R, Heymsfield S, Bosello O. Body fat distribution before and after weight gain in anorexia nervosa. Int J Obes Relat Metab Disord. 1997; 21 33-36
- 34 Lara-Castro C, Weinsier RL, Hunter GR, Desmond R. Visceral adipose tissue in women: longitudinal study of the effects of fat gain, time, and race. Obes Res. 2002; 10 868-874
- 35 Gunderson EP, Sternfeld B, Wellons MF, Whitmer RA, Chiang V, Quesenberry Jr CP, Lewis CE, Sidney S. Childbearing may increase visceral adipose tissue independent of overall increase in body fat. Obesity. 2008; 16 1078-1084
- 36 Lovejoy JC, Champagne CM, de Jonge L, Xie H, Smith SR. Increased visceral fat and decreased energy expenditure during the menopausal transition. Int J Obes. 2008; 32 949-958
- 37 Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, Vasan RS, Murabito JM, Meigs JB, Cupples LA, D’Agostino Sr RB, O’Donnell CJ. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. 2007; 116 39-48
- 38 Hairston KG, Bryer-Ash M, Norris JM, Haffner S, Bowden DW, Wagenknecht LE. Sleep duration and five-year abdominal fat accumulation in a minority cohort: the IRAS family study. Sleep. 2010; 33 289-295
- 39 Ross R, Léger L, Guardo R, De Guise J, Pike BG. Adipose tissue volume measured by magnetic resonance imaging and computerized tomography in rats. J Appl Physiol. 1991; 70 2164-2172
- 40 Tang H, Vasselli JR, Wu EX, Boozer CN, Gallagher D. High-resolution magnetic resonance imaging tracks changes in organ and tissue mass in obese and aging rats. Am J Physiol Regul Integr Comp Physiol. 2002; 282 R890-R899
- 41 Neel JV. Diabetes mellitus: a “thrifty” genotype rendered detrimental by progress. Am J Hum Genet. 1962; 14 353-361
- 42 Bellisari A. Evolutionary origins of obesity. Obes Rev. 2008; 9 165-180
- 43 Thomas EL, Saeed N, Hajnal JV, Brynes A, Goldstone AP, Frost G, Bell JD. Magnetic resonance imaging of total body fat. J Appl Physiol. 1998; 85 1778-1785
Correspondence
N. J. Crowther
Associate Professor
Department of Chemical
Pathology
National Health Laboratory
Service
University of the Witwatersrand
Faculty of Health Sciences
7 York Road
Parktown 2193
Johannesburg
South Africa
Phone: +27/11/489 8525
Fax: +27/11/489 8451
Email: nigel.crowther@nhls.ac.za