Hostname: page-component-848d4c4894-r5zm4 Total loading time: 0 Render date: 2024-06-16T19:11:42.425Z Has data issue: false hasContentIssue false

Visceral fat and insulin resistance — causative or correlative?

Published online by Cambridge University Press:  09 March 2007

Keith N. Frayn*
Oxford Lipid Metabolism Group, Radcliffe Infirmary, Oxford, OX2 6HE, UK
Corresponding author: K. N. Frayn, fax +44 1865 224652, email
Rights & Permissions [Opens in a new window]


Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

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.

Research Article
Copyright © The Nutrition Society 2000


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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle Scholar
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.CrossRefGoogle ScholarPubMed
Arner, P (1997) Impact of visceral fat. International Journal of Obesity 21, (Suppl. 2), S20.Google Scholar
Arner, P (1999) Catecholamine-induced lipolysis in obesity. International Journal of Obesity 23, (Suppl. 1), 1013.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Björntorp, P (1988) Abdominal obesity and the development of noninsulin-dependent diabetes mellitus. Diabetes/Metabolism Reviews 4, 615622.CrossRefGoogle ScholarPubMed
Björntorp, P (1990) ‘Portal’ adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 10, 493496.CrossRefGoogle Scholar
Björntorp, P (1996) The regulation of adipose tissue distribution in humans. International Journal of Obesity 20, 291302.Google ScholarPubMed
Björntorp, P (1997) Neuroendocrine factors in obesity. Journal of Endocrinology 155, 193195.CrossRefGoogle ScholarPubMed
Björntorp, P (1997) Stress and cardiovascular disease. Acta Physiologica Scandinavica Supplement 640, 144148.Google ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.Google ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Frayn, KN, Coppack, SW & Humphreys, SM (1993) Subcutaneous adipose tissue metabolism studied by local catheterization. International Journal of Obesity 17(Suppl. 3), S18-S21.Google ScholarPubMed
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.Google ScholarPubMed
Guo, Z, Hensrud, DD, Johnson, CM & Jensen, MD (1999) Regional postprandial fatty acid metabolism in different obesity phenotypes. Diabetes 48, 15861592.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Kissebah, AH & Krakower, GR (1994) Regional adiposity and morbidity. Physiological Reviews 74, 761811.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle Scholar
Martin, ML & Jensen, MD (1991) Effects of body fat distribution on regional lipolysis in obesity. Journal of Clinical Investigation 88, 609613.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
Mohamed-Ali, V, Pinkney, JH & Coppack, SW (1998) Adipose tissue as an endocrine and paracrine organ. International Journal of Obesity 22, 11451158.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
östman, J, Arner, P, Engfeldt, P & Kager, L (1979) Regional differences in the control of lipolysis in human adipose tissue. Metabolism 28, 11981205.CrossRefGoogle ScholarPubMed
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.Google ScholarPubMed
Pereira, ME & Pond, CM (1995) Organization of white adipose tissue in Lemuridae. American Journal of Primatology 35, 113.CrossRefGoogle ScholarPubMed
Reaven, GM (1988) Role of insulin resistance in human disease. Diabetes 37, 15951607.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Siiteri, PK (1987) Adipose tissue as a source of hormones. American Journal of Clinical Nutrition 45, 277282.CrossRefGoogle ScholarPubMed
Snyder, WS (1975). Report of the Task Force on Man, International Commission on Radiological Protection. Oxford: Pergamon Press.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Vague, J (1947) La différenciation sexuelle, facteur déterminant des formes de l'obésité. La Presse Médicale 30, 339340.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed