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Metabolic impact of body fat distribution

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Abstract

Many studies have shown that fat distribution influences metabolism independently of the effects of total body fat stores. The accumulation of fat in the abdominal area, particularly in the visceral fat compartment, seems to be associated with an increased risk to display complications such as insulin resistance, diabetes, dyslipidemias and atherosclerosis. As reviewed in this paper, the mechanisms explaining this impact of fat distribution is not clearly established, although evidence suggests that free-fatty acids, leptin, TNF-α, PPAR-γ, and F are directly or indirectly involved in this process. Despite a lot of research has yet to be performed to mechanistically characterize the impact of visceral fat on the metabolic profile, there is enough consensus in the literature about its effect to justify its consideration in a clinical setting. In this regard, the use of waist circumference as a clinical marker of variations in visceral fat is highly relevant and should be encouraged. This review also presents an evolutionary perspective according to which body fat gain would have been and may still remain an adaptation that helps to deal with stress and inflammation.

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References

  1. Vague J. La différenciation sexuelle, facteur déterminant des formes de l’obésité. Presse Méd. 1947, 55: 339–340.

    CAS  PubMed  Google Scholar 

  2. Lapidus L., Bengtsson C., Larsson B., Pennert K., Rybo E., Sjöström L. Distribution of adipose tissue and risk of cardiovascular disease and death: a 12 year follow-up of participants in the population study of women in Gothenburg, Sweden. B.M.J. 1984, 289: 1258–1261.

    Article  Google Scholar 

  3. Larsson B., Svärdsudd K., Welin L., Wilhelmsen L., Björntorp P., Tibblin G. Abdominal adipose tissue distribution, obesity and risk of cardiovascular disease and death: 13 year follow-up of participants in the study of men born in 1913. B.M.J. 1984, 288: 1401–1404.

    Article  CAS  Google Scholar 

  4. Ohlson L.O., Larsson B., Svärdsudd K. et al. The influence of body fat distribution on the incidence of diabetes mellitus — 13.5 years of follow-up of the participants in the study of men born in 1913. Diabetes 1985, 34: 1055–1058.

    Article  CAS  PubMed  Google Scholar 

  5. Donahue R.P., Abbott R.D., Bloom E., Reed D.M., Yano K. Central obesity and coronary heart disease in men. Lancet 1987, 1: 821–824.

    Article  CAS  PubMed  Google Scholar 

  6. Kissebah A.H. Central obesity: measurement and metabolic effects. Diabetes Rev. 1997, 5: 8–20.

    Google Scholar 

  7. Björntorp P. Metabolic implications of body fat distribution. Diabetes Care 1991, 14: 1132–1143.

    Article  PubMed  Google Scholar 

  8. Fried S.K., Leibel R.L., Edens N.K., Kral J.G. Lipolysis in intraabdominal adipose tissues of obese women. Obes. Res. 1993, 1: 443–448.

    Article  CAS  PubMed  Google Scholar 

  9. Mauriège P., Galitzky J., Berlan M., Lafontan M. Heterogeneous distribution of ß- and a2-adrenoceptor binding sites in human fat cells from various deposits: functional consequences. Eur. J. Clin. Invest. 1987, 17: 156–165.

    Article  PubMed  Google Scholar 

  10. Mauriège P., Marette A., Atgié C. et al. Regional variation in adipose tissue metabolism of severely obese women. J. Lipid Res. 1995, 36: 672–684.

    PubMed  Google Scholar 

  11. Hellmér J., Marcus C., Sonnenfeld T., Arner P. Mechanisms for differences in lipolysis between human subcutaneous and omental fat cells. J. Clin. Endocrinol. Metab. 1992, 75: 15–20.

    PubMed  Google Scholar 

  12. Lönnqvist F., Krief S., Strosberg A.D., Nyberg B., Emorine L.J., Arner P. Evidence of a functional ß3-adrenoceptor in man. Br. J. Pharmacol. 1993, 110: 929–936.

    Article  PubMed  Google Scholar 

  13. Vikman H.L., Savola J.M., Raasmaja A., Ohisalo J.J. α2A-adrenergic regulation of cyclic AMP accumulation and lipolysis in human omental and subcutaneous adipocytes. Int. J. Obes. 1996, 20: 185–189.

    CAS  Google Scholar 

  14. Hoffstedt J., Arner P., Hellers G., Lönnqvist F. Variation in adrenergic regulation of lipolysis between omental and subcutaneous adipocytes from obese and non-obese men. J. Lipid Res. 1997, 38: 795–804.

    CAS  PubMed  Google Scholar 

  15. Arner P. Not all fat is alike. Lancet 1998, 351: 1301–1302.

    Article  CAS  PubMed  Google Scholar 

  16. Björntorp P. “Portal“ adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 1990, 10: 493–496.

    Article  PubMed  Google Scholar 

  17. Björntorp P. Visceral obesity: a civilization syndrome. Obes. Res. 1993, 1: 206–222.

    Article  PubMed  Google Scholar 

  18. Kissebah A.H., Krakower G.R. Regional adiposity and morbidity. Physiol. Rev. 1994, 74: 761–811.

    CAS  PubMed  Google Scholar 

  19. Frayn K.N., Williams C.M., Arner P. Are increased plasma non-esterified fatty acid concentrations a risk marker for coronary heart disease and other chronic diseases? Clin. Sci. (Lond.), 1996, 90: 243–253.

    CAS  Google Scholar 

  20. Boden G. Pathogenesis of type 2 diabetes. Insulin resistance. Endocrinol. Metab. Clin. North Am. 2001, 30: 801–815.

    Article  CAS  PubMed  Google Scholar 

  21. Zhang Y., Proenca R., Maffei M., Barone M., Leopold L., Friedmann J.M. Positional cloning of the mouse obese gene and its human homologue. Nature 1994, 372: 425–432.

    Article  CAS  PubMed  Google Scholar 

  22. Pelleymounter M.A., Cullen M.J., Baker M.B. et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995, 269: 540–543.

    Article  CAS  PubMed  Google Scholar 

  23. Tartaglia L.A., Dembsky M., Wenig X. et al. Identification and expression cloning of a leptin receptor, OB-R. Cell 1995, 83: 1263–1271.

    Article  CAS  PubMed  Google Scholar 

  24. Couillard C., Mauriege P., Prud’homme D. et al. Plasma leptin concentrations: gender differences and associations with metabolic risk factors for cardiovascular disease. Diabetologia 1997, 40: 1178–1184.

    Article  CAS  PubMed  Google Scholar 

  25. Hickey M.S., Israel R.G., Gardiner S.N. et al. Gender differences in serum leptin levels in humans. Biochem. Mol. Med. 1996, 59: 1–6.

    Article  CAS  PubMed  Google Scholar 

  26. Nagy T.R., Gower B.A., Trowbridge C.A., Dezenberg C., Shewchuk R.M., Goran M.I. Effects of gender, ethnicity, body composition, and fat distribution on serum leptin concentrations in children. J. Clin. Endocrinol. Metab. 1997, 82: 2148–2152.

    CAS  PubMed  Google Scholar 

  27. Ronnemaa T., Karonen S.L., Rissanen A., Koskenvuo M., Koivisto V.A. Relation between plasma leptin levels and measures of body fat in identical twins discordant for obesity. Ann. Intern. Med. 1997, 126: 26–31.

    Article  CAS  PubMed  Google Scholar 

  28. Lönnqvist F., Wennlund A., Arner P. Relationship between circulating leptin and peripheral fat distribution in obese subjects. Int. J. Obes. 1997, 21: 255–260.

    Article  Google Scholar 

  29. Minocci A., Savia G., Lucantoni R. et al. Leptin plasma concentrations are dependent on body fat distribution in obese patients. Int. J. Obes. 2000, 24: 1139–1144.

    Article  CAS  Google Scholar 

  30. Cnop M., Landchild M.J., Vidal J. et al. The concurrent accumulation of intra-abdominal and subcutaneous fat explains the association between insulin resistance and plasma leptin concentrations. Distinct metabolic effects of two fat compartments. Diabetes 2002, 51: 1005–1015.

    Article  CAS  PubMed  Google Scholar 

  31. Shimabukuro M., Koyama K., Chen G. et al. Direct antidiabetic effect of leptin through triglyceride depletion of tissues. Proc. Natl. Acad. Sci. USA 1997, 94: 4637–4641.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Unger R.H., Zhou Y.T., Orci L. Regulation of fatty acid homeostasis in cells: novel role of leptin. Proc. Natl. Acad. Sci. USA 1999, 96: 2327–2332.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Unger R.H., Orci L. Lipotoxic diseases of nonadipose tissues in obesity. Int. J. Obes. 2000, 24: S28–S32.

    Article  CAS  Google Scholar 

  34. Liuzzi A., Savia G., Tagliaferri M. et al. Serum leptin concentration in moderate and severe obesity: relationship with clinical, anthropometric and metabolic factors. Int. J. Obes. 1999, 23: 1066–1073.

    Article  CAS  Google Scholar 

  35. Holub M., Zwiauer K., Winkler C. et al. Relation of plasma leptin to lipoproteins in overweight children undergoing weight reduction. Int. J. Obes. 1999, 23: 60–66.

    Article  CAS  Google Scholar 

  36. Krempler F., Breban D., Oberkofler H. et al. Leptin, peroxisome proliferator-activated receptor-γ, and CCAAT/enhancer binding protein-α mRNA expression in adipose tissue of humans and their relation to cardiovascular risk factors. Arterioscler. Thromb. Vasc. Biol. 2000, 20: 443–449.

    Article  CAS  PubMed  Google Scholar 

  37. Hotamisligil G.S., Shargill N.S., Spiegelmann B.M. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993, 259: 87–91.

    Article  CAS  PubMed  Google Scholar 

  38. Hotamisligil G.S., Budavari A., Murray D., Spiegelmann B.M. Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes. J. Clin. Invest. 1994, 94: 1543–1549.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Hotamisligil G.S., Peraldi P., Budavari A., Ellis R., White M.F., Spiegelman B.M. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity- induced insulin resistance. Science 1996, 271: 665–668.

    Article  CAS  PubMed  Google Scholar 

  40. Hotamisligil G.S., Spiegelman B.M. Tumor necrosis factor a: a key component of the obesity-diabetes link. Diabetes 1994, 43: 1271–1278.

    Article  CAS  PubMed  Google Scholar 

  41. Kern P.A., Saghizadeh M., Ong J.M., Bosch R.J., Deem R., Simsolo R.B. The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. J. Clin. Invest 1995, 95: 2111–2119.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Hotamisligil G.S., Arner P., Caro J.F., Atkinson R.L., Spiegelman B.M. Increased adipose tissue expression of tumor necrosis factor-a in human obesity and insulin resistance. J. Clin. Invest. 1995, 95: 2409–2415.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Saghizadeh M., Ong J.M., Garvey W.T., Henry R.R., Kern P.A. The expression of TNF-a by human muscle. Relationship to insulin resistance. J. Clin. Invest. 1996, 97: 1111–1116.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Bertin E., Nguyen P., Guenounou M., Durlach V., Potron G., Leutenegger M. Plasma levels of tumor necrosis factor- alpha (TNF-alpha) are essentially dependent on visceral fat amount in type 2 diabetic patients. Diabetes Metab. 2000, 26: 178–182.

    CAS  PubMed  Google Scholar 

  45. Hotamisligil G.S., The role of TNF alpha and TNF receptors in obesity and insulin resistance. J. Int. Med. 1999, 245: 621–625.

    Article  CAS  Google Scholar 

  46. Oefi F., Hurel S., Newkirk J., Sopwith M., Taylor R. Effects of an engineered human anti-TNF-alpha antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes 1998, 47: 721–726.

    Article  Google Scholar 

  47. Pincelli A.I., Brunani A., Scacchi M. et al. The serum concentration of tumor necrosis factor alpha is not an index of growth-hormone- or obesity-induced insulin resistance. Horm. Res. 2001, 55: 57–64.

    Article  CAS  PubMed  Google Scholar 

  48. Cseh K., Winkler G., Melczer Z., Baranyi E. The role of tumour necrosis factor (TNF)- a resistance in obesity and insulin resistance. Diabetologia 2000, 43: 525.

    Article  CAS  PubMed  Google Scholar 

  49. Marin P., Andersson B., Ottosson M. et al. The morphology and metabolism of intraabdominal adipose tissue in men. Metabolism 1992, 41: 1242–1248.

    Article  CAS  PubMed  Google Scholar 

  50. Bollinder 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.

    Article  Google Scholar 

  51. Fernández-Real J.-M., Ricart W. Insulin resistance and inflammation in an evolutionary perspective: the contribution of cytokine genotype/phenotype to thriftiness. Diabetologia 1999, 42: 1367–1374.

    Article  PubMed  Google Scholar 

  52. Kliewer S.A., Umesono K., Noonan D.J., Heyman R.A., Evans R.M. Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptor. Nature 1992, 358: 771–774.

    Article  CAS  PubMed  Google Scholar 

  53. Tontonoz P., Hu E., Graves R.A., Budavari A.I., Spiegelman B.M. MPPAR?2: tissue-specific regulator of an adipocyte enhancer. Genes Dev. 1994, 8: 1224–1234.

    Article  CAS  PubMed  Google Scholar 

  54. Schoonjans K., Staels B., Auwerx J. The peroxisome proliferator activated receptors (PPARS) and their effect on lipid metabolism and adipocyte differentiation. Biochem. Biophys. Acta 1996, 1302: 93–109.

    Article  CAS  PubMed  Google Scholar 

  55. Vidal-Puig A., Considine R.V., Jimenez-Linan M. et al. Peroxisome proliferator-activated receptor gene expression in human tissues: effects of obesity, weight loss, and regulation by insulin and glucocorticoids. J. Clin. Invest. 1997, 99: 2416–2422.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Lefebvre A.M., Laville M., Vega N. et al. Depot-specific differences in adipose tissue gene expression in lean and obese subjects. Diabetes 1998, 47: 98–103.

    Article  CAS  PubMed  Google Scholar 

  57. Rieusset J., Andreelli F., Auboeuf D. et al. Insulin acutely regulates the expression of the peroxisome proliferatoractivated receptor-? in human adipocytes. Diabetes 1999, 48: 699–705.

    Article  CAS  PubMed  Google Scholar 

  58. Klausner H., Heimberg M. Effect of adrenal-cortical hormones on release of triglycerides and glucose by liver. Am. J. Physiol. 1967, 212: 1236–1246.

    CAS  PubMed  Google Scholar 

  59. Khani S., Tayek J.A. Cortisol increases gluconeogenesis in humans: its role in the metabolic syndrome. Clin. Sci. (Lond.) 2001, 101: 739–747.

    Article  CAS  Google Scholar 

  60. Cigolini M., Smith U. Human adipose tissue in culture. VIII. Studies on the insulin-antagonistic effect of glucocorticoids. Metabolism 1979, 28: 502–510.

    Article  CAS  PubMed  Google Scholar 

  61. Holmäng P., Björntorp P. The effects of cortisol on insulin sensitivity in muscle. Acta Physiol. Scand., 1992, 144: 425–431.

    Article  PubMed  Google Scholar 

  62. Whitworth J.A., Mangos G.J., Kelly J.J. Cushing, cortisol, and cardiovascular disease. Hypertension 2000, 36: 912–916.

    Article  CAS  PubMed  Google Scholar 

  63. Marin P., Darin M., Amemiya T., Andersson B., Jern S., Bjorntörp P. Cortisol secretion in relation to body fat distribution in obese premenopausal women. Metabolism 1992, 41: 882–886.

    Article  CAS  PubMed  Google Scholar 

  64. Walker B.R., Soderberg S., Lindahl B., Olsson T. Independent effects of obesity and cortisol in predicting cardiovascular risk factors in men and women. J. Intern. Med. 2000, 247: 198–204.

    Article  CAS  PubMed  Google Scholar 

  65. Lottenberg S.A., Giannella-Neto D., Derendorf H., et al. Effect of fat distribution on pharmacokinetics of cortisol in obesity. Int. J. Clin. Pharmacol. Ther. 1998, 36: 501–505.

    CAS  PubMed  Google Scholar 

  66. Rebuffé-Scrive M., Lundholm K., Björntorp P. Glucocorticoid hormone binding to human adipose tissue. Eur. J. Clin. Invest. 1985, 15: 267–271.

    Article  PubMed  Google Scholar 

  67. Bujalska I.J., Kumar S., Stewart P.M. Does central obesity reflect “Cushing’s disease of the omentum?”. Lancet 1997, 349: 1210–1213.

    Article  CAS  PubMed  Google Scholar 

  68. Björntorp P., Rosmond R. The metabolic syndrome — a neuroendrocrine disorder? Br. J. Nutr. 2000, 83 (Suppl. 1): S49–S57.

    PubMed  Google Scholar 

  69. Rosmond R., Dallman M.F., Björntorp P. Stress-related cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities. J. Clin. Endocrinol. Metab. 1998, 83: 1853–1859.

    CAS  PubMed  Google Scholar 

  70. Rankinen T., Kim S.Y., Perusse L., Després J.P., Bouchard C. The prediction of abdominal visceral fat level from body composition and anthropometry: ROC analysis. Int. J. Obes. 1999, 23: 801–809.

    Article  CAS  Google Scholar 

  71. Després J.P., Prud’homme D., Pouliot M.C., Tremblay A., Bouchard A., Bouchard C. Estimation of deep abdominal adipose-tissue accumulation from simple anthroprometric measurement in men. Am. J. Clin. Nutr. 1991, 54: 471–477.

    PubMed  Google Scholar 

  72. National Heart, Lung, and Blood Institute, Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. The evidence report. Obes. Res. 1998, 6 (Suppl. 2): 515–209S.

    Google Scholar 

  73. Shor-Posner G., Campa A., Zhang G. et al. When obesity is desirable: a longitudinal study of the Miami HIV-1-infected drug abusers (MIDAS) cohort. J. Acquir. Immun. Defic. Syndr. 2000, 23: 81–88.

    Article  CAS  Google Scholar 

  74. Epel E.E., Moyer A.E., Martin C.D. et al. Stress-induced cortisol, mood, and fat distribution in men. Obes. Res. 1999, 7: 9–15.

    Article  CAS  PubMed  Google Scholar 

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Gasteyger, C., Tremblay, A. Metabolic impact of body fat distribution. J Endocrinol Invest 25, 876–883 (2002). https://doi.org/10.1007/BF03344051

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