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Visceral fat and insulin resistance — causative or correlative?

  • Keith N. Frayn (a1)


The association between abdominal fat accumulation and risk of chronic diseases, including type II diabetes and coronary heart disease, has long been recognized. Insulin resistance may be a key factor in this link. Many studies have pointed to an association between insulin resistance and intra-abdominal fat accumulation (visceral obesity). However there is no clear proof of a causal link between visceral fat accumulation and insulin resistance. In assessing the probability of a causal link, it is useful to consider potential mechanisms. One such potential causal link is the release of non-esterified fatty acids from visceral fat into the portal vein, so that they have direct effects on hepatic metabolism. Visceral fat has been shown in many studies to exhibit a high rate of lipolysis compared with subcutaneous fat depots. However, if the idea that visceral fat releases fatty acids into the portal vein at a high rate is examined critically, a number of difficulties appear. Not least of these is the fact that continued high rates of lipolysis should lead to the disappearance of the visceral fat depot, unless these high rates of fat mobilization are matched by high rates of fat deposition. There is far less evidence for high rates of fat deposition in visceral adipose tissue, and some contrary evidence. Evidence for high rates of visceral lipolysis in vivo from studies involving catheterization of the portal vein is not strong. If this potential link is discounted, then other reasons for the relationship between visceral fat and insulin resistance must be considered. One is that there is no direct causal link, but both co-correlate with some other variable. A possibility is that this other variable is subcutaneous abdominal fat, which usually outweighs intra-abdominal fat several-fold. Subcutaneous fat probably plays the major role in determining systemic plasma non-esterified fatty acid concentrations, which are relevant in determining insulin resistance. In conclusion, there is at present no proof of a causal link between visceral fat accumulation and insulin resistance, or the associated metabolic syndrome. The possibility of co-correlation with some other factor, such as subcutaneous abdominal fat accumulation, must not be forgotten.

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Corresponding author

Corresponding author: K. N. Frayn, fax +44 1865 224652, email


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Abate, N, Garg, A, Peshock, RM, Stray, Gundersen, J, & Grundy, SM (1995) Relationships of generalized and regional adiposity to insulin sensitivity in men. Journal of Clinical Investigation 96, 8898.
Abate, N, Garg, A, Peshock, RM, Stray-Gundersen, J, Adams-Huet, B & Grundy, SM (1996) Relationship of generalized and regional adiposity to insulin sensitivity in men with NIDDM. Diabetes 45, 16841693.
Abate, N, Garg, A, Coleman, R, Grundy, SM & Peshock, RM (1997) Prediction of total subcutaneous abdominal, intraperitoneal, and retroperitoneal adipose tissue masses in men by a single axial magnetic resonance imaging slice. American Journal of Clinical Nutrition 65, 403408.
Alessi, MC, Peiretti, F, Morange, P, Henry, M, Nalbone, G, Juhan-Vague, I (1997) Production of plasminogen activator inhibitor 1 by human adipose tissue: possible link between visceral fat accumulation and vascular disease. Diabetes 46, 860867.
Arner, P (1997) Impact of visceral fat. International Journal of Obesity 21, (Suppl. 2), S20.
Arner, P (1999) Catecholamine-induced lipolysis in obesity. International Journal of Obesity 23, (Suppl. 1), 1013.
Ashwell, M, Cole, TJ & Dixon, AK (1985) Obesity: new insight into the anthropometric classification of fat distribution shown by computed tomography. British Medical Journal 290, 16921694.
Barzilai, N, She, L, Liu, BQ, Vuguin, P, Cohen, P, Wang, J & Rossetti, L (1999) Surgical removal of visceral fat reverses hepatic insulin resistance. Diabetes 48, 9498.
Björkman, O, Eriksson, LS, Nyberg, B & Wahren, J (1990) Gut exchange of glucose and lactate in basal state and after oral glucose ingestion in postoperative patients. Diabetes 39, 747751.
Björntorp, P (1988) Abdominal obesity and the development of noninsulin-dependent diabetes mellitus. Diabetes/Metabolism Reviews 4, 615622.
Björntorp, P (1990) ‘Portal’ adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 10, 493496.
Björntorp, P (1996) The regulation of adipose tissue distribution in humans. International Journal of Obesity 20, 291302.
Björntorp, P (1997) Neuroendocrine factors in obesity. Journal of Endocrinology 155, 193195.
Björntorp, P (1997) Stress and cardiovascular disease. Acta Physiologica Scandinavica Supplement 640, 144148.
Blackard, WG, Clore, JN, Glickman, PS, Nestler, JE & Kellum, JM (1993) Insulin sensitivity of splanchnic and peripheral adipose tissue in vivo in morbidly obese man. Metabolism 42, 11951200.
Després, JP, Nadeau, A, Tremblay, A, Ferland, M, Moorjani, S, Lupien, PJ, Thériault, G, Pinault, S & Bouchard, C (1989) Role of deep abdominal fat in the association between regional adipose tissue distribution and glucose tolerance in obese women. Diabetes 38, 304309.
Engfeldt, P & Arner, P (1988) Lipolysis in human adipocytes, effects of cell size, age and of regional differences. Hormone and Metabolic Research Supplement 19, 2629.
Ferrannini, E, Barrett, EJ, Bevilacqua, S & DeFronzo, RA (1983) Effect of fatty acids on glucose production and utilization in man. Journal of Clinical Investigation 72, 17371747.
Folsom, AR, Kaye, SA, Sellers, TA, Hong, C-P, Cerhan, JR, Potter, JD & Prineas, RJ (1993) Body fat distribution and 5-year risk of death in older women. Journal of the American Medical Association 269, 483487.
Fontbonne, A, Thibult, N, Eschwège, E, Ducimetière, P (1992) Body fat distribution and coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes mellitus: the Paris Prospective Study, 15-year follow up. Diabetologia 35, 464468.
Frayn, KN, Coppack, SW & Humphreys, SM (1993) Subcutaneous adipose tissue metabolism studied by local catheterization. International Journal of Obesity 17(Suppl. 3), S18-S21.
Fried, SK, Bunkin, DA & Greenberg, AS (1998) Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. Journal of Clinical Endocrinology and Metabolism 83, 847–50.
Guo, Z, Hensrud, DD, Johnson, CM & Jensen, MD (1999) Regional postprandial fatty acid metabolism in different obesity phenotypes. Diabetes 48, 15861592.
Hagenfeldt, L, Wahren, J, Pernow, B & Raf, L (1972) Uptake of individual free fatty acids by skeletal muscle and liver in man. Journal of Clinical Investigation 51, 23242330.
Havel, RJ, Kane, JP, Balasse, EO, Segel, N & Basso, LV (1970) Splanchnic metabolism of free fatty acids and production of triglycerides of very low density lipoproteins in normotriglyceridemic and hypertriglyceridemic humans. Journal of Clinical Investigation 49, 20172035.
Hotamisligil, GS, Arner, P, Caro, JF, Atkinson, RL & Spiegelman, BM (1995) Increased adipose tissue expression of tumor necrosis factor-α in human obesity and insulin resistance. Journal of Clinical Investigation 95, 24092415.
Jeppesen, J, Hollenbeck, CB, Zhou, M-Y, Coulston, AM, Jones, C, Chen, Y-DI & Reaven, GM (1995) Relation between insulin resistance, hyperinsulinemia, postheparin plasma lipoprotein lipase activity, and postprandial lipemia. Arteriosclerosis, Thrombosis, and Vascular Biology 15, 320324.
Kalmijn, S, Curb, JD, Rodriguez, BL, Yano, K & Abbott, RD (1999) The association of body weight and anthropometry with mortality in elderly men: The Honolulu Heart Program. International Journal of Obesity 23, 395402.
Kissebah, AH & Krakower, GR (1994) Regional adiposity and morbidity. Physiological Reviews 74, 761811.
Landin, K, Stigendal, L, Eriksson, E, Krotkiewski, M, Risberg, B, Tengborn, L & Smith, U (1990) Abdominal obesity is associated with an impaired fibrinolytic activity and elevated plasminogen activator inhibitor-1. Metabolism 39, 10441048.
Lefebvre, A-M, Laville, M, Vega, N, Riou, JP, van Gaal, L, Auwerx, J & Vidal, H (1998) Depot-specific differences in adipose tissue gene expression in lean and obese subjects. Diabetes 47, 98103.
Mårin, P, Andersson, B, Ottosson, M, Olbe, L, Chowdhury, B, Kvist, H, Holm, G, Sjöström, L, Björntorp, P (1992) The morphology and metabolism of intra-abdominal adipose tissue in men. Metabolism 41, 12421248.
Martin, ML & Jensen, MD (1991) Effects of body fat distribution on regional lipolysis in obesity. Journal of Clinical Investigation 88, 609613.
Maslowska, MH, Sniderman, AD, MacLean, LD & Cianflone, K (1993) Regional differences in triacylglycerol synthesis in adipose tissue and in cultured preadipocytes. Journal of Lipid Research 34, 219228.
Mauriège, P, Galitzky, J, Berlan, M & Lafontan, M (1987) Heterogeneous distribution of beta and alpha-2 adrenoceptor binding sites in human fat cells from various fat deposits: functional consequences. European Journal of Clinical Investigation 17, 156165.
Mauriège, P, Marette, A, Atgie, C, Bouchard, C, Theriault, G, Bukowiecki, LK, Marceau, P, Biron, S, Nadeau, A, Després, JP (1995) Regional variation in adipose tissue metabolism of severely obese premenopausal women. Journal of Lipid Research 36, 672684.
Misra, A, Garg, A, Abate, N, Peshock, RM, Stray-Gundersen, J (1997) Relationship of anterior and posterior subcutaneous abdominal fat to insulin sensitivity in nondiabetic men. Obesity Research 5, 9399.
Mohamed-Ali, V, Goodrick, S, Rawesh, A, Katz, DR, Miles, JM, Yudkin, JS, Klein, S & Coppack, SW (1997) Subcutaneous adipose tissue secretes interleukin-6 but not tumor necrosis-factor-α in vivo. Journal of Clinical Endocrinology and Metabolism 82, 41964200.
Mohamed-Ali, V, Pinkney, JH & Coppack, SW (1998) Adipose tissue as an endocrine and paracrine organ. International Journal of Obesity 22, 11451158.
Montague, CT, Prins, JB, Sanders, L, Zhang, J, Sewter, CP, Digby, J, Byrne, CD, O'Rahilly, S (1998) Depot-related gene expression in human subcutaneous and omental adipocytes. Diabetes 47, 13841391.
östman, J, Arner, P, Engfeldt, P & Kager, L (1979) Regional differences in the control of lipolysis in human adipose tissue. Metabolism 28, 11981205.
Pedersen, SB, Jønler, M & Richelsen, B (1994) Characterization of regional and gender differences in glucocorticoid receptors and lipoprotein lipase activity in human adipose tissue. Journal of Clinical Endocrinology and Metabolism 78, 13541359.
Pereira, ME & Pond, CM (1995) Organization of white adipose tissue in Lemuridae. American Journal of Primatology 35, 113.
Reaven, GM (1988) Role of insulin resistance in human disease. Diabetes 37, 15951607.
Reaven, GM, Chen, Y-DI & Krauss, RM (1992) Resistance to insulin-mediated glucose uptake and hyperinsulinaemia in subjects with small, dense LDL. Circulation 86 (Suppl.), I-73.
Ross, R, Leger, L, Morris, D, de Guise, J & Guardo, R (1992) Quantification of adipose tissue by MRI: relationship with anthropometric variables. Journal of Applied Physiology 72, 787795.
Saghizadeh, M, Ong, JM, Garvey, WT, Henry, RR & Kern, PA (1996) The expression of TNF-α by human muscle. Relationship to insulin resistance. Journal of Clinical Investigation 97, 11111116.
Seidell, JC & Bouchard, C (1997) Visceral fat in relation to health: is it a major culprit or simply an innocent bystander?. International Journal of Obesity 21, 626631.
Siiteri, PK (1987) Adipose tissue as a source of hormones. American Journal of Clinical Nutrition 45, 277282.
Snyder, WS (1975). Report of the Task Force on Man, International Commission on Radiological Protection. Oxford: Pergamon Press.
Svedberg, J, Björntorp, P, Smith, U, Lönnroth, P (1990) Free-fatty acid inhibition of insulin binding, degradation, and action in isolated rat hepatocytes. Diabetes 39, 570574.
Tavernier, G, Galitzky, J, Valet, P, Remaury, A, Bouloumie, A, Lafontan, M & Langin, D (1995) Molecular mechanisms underlying regional variations of catecholamine-induced lipolysis in rat adipocytes. American Journal of Physiology 268, E1135-E1142.
Thomas, EL, Saeed, N, Hajnal, JV, Brynes, A, Goldstone, AP, Frost, G & Bell, JD (1998) Magnetic resonance imaging of total body fat. Journal of Applied Physiology 85, 17781785.
Vague, J (1947) La différenciation sexuelle, facteur déterminant des formes de l'obésité. La Presse Médicale 30, 339340.
Vague, J (1956) The degree of masculine differentiation of obesities: a factor determining predisposition to diabetes, atherosclerosis, gout and uric calculous disease. American Journal of Clinical Nutrition 4, 2034.
Van Harmelen, V, Lönnqvist, F, Thörne, A, Wennlund, A, Large, V, Reynisdottir, S & Arner, P (1997) Noradrenaline-induced lipolysis in isolated mesenteric, omental and subcutaneous adipocytes from obese subjects. International Journal of Obesity 21, 972979.
Van Harmelen, V, Reynisdottir, S, Eriksson, P, Thörne, A, Hoffstedt, J, Lönnqvist, F & Arner, P (1998) Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes 47, 913917.
Wiesenthal, SR, Sandhu, H, McCall, RH, Tchipashvili, V, Yoshii, H, Polonsky, K, Shi, ZQ, Lewis, GF, Mari, A & Giacca, A (1999) Free fatty acids impair hepatic insulin extraction in vivo. Diabetes 48, 766774.



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