Depot-Specific Hormonal Characteristics of Subcutaneous and Visceral Adipose Tissue and their Relation to the Metabolic Syndrome

B. L. Wajchenberg; D. Giannella-Neto; M. E. R. da Silva; R. F. Santos

doi:10.1055/s-2002-38256

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2002; 34(11/12): 616-621
DOI: 10.1055/s-2002-38256

Review

Depot-Specific Hormonal Characteristics of Subcutaneous and Visceral Adipose Tissue and their Relation to the Metabolic Syndrome

B. L. Wajchenberg ¹ , D. Giannella-Neto ^1, ² , M. E. R. da Silva ^1, ³ , R. F. Santos ^1, ³

¹ Endocrine Service (Diabetes), Medical Investigation Laboratories, Hospital das Clinicas, São Paulo, SP, Brazil
² 25 (LIM 25), Hospital das Clinicas, São Paulo, SP, Brazil
³ 18 (LIM 18), Hospital das Clinicas, São Paulo, SP, Brazil

Abstract

Visceral adipose tissue (VAT) imaged by computed tomography (CT) or magnetic resonance imaging (MRI) is associated with the metabolic syndrome features, being morphologically and functionally different from subcutaneous adipose tissue (SAT). Insulin effect is lower and catecholamine effect higher in visceral adipose tissue, with its metabolites and its secretions draining through portal system, partially at least, to the liver. Thus, visceral cells transfer and release fatty acids more extensively, have increased glucocorticoid and reduced thiazolidinedione responses, produce more angiotensinogen, interleukin-6 and plasminogen activator inhibitor-1, and secrete less leptin and adiponectin than SAT. Furthermore, there are regional differences in the intrinsic characteristics of the preadipocytes, with those of SAT presenting greater differentiation and fat cell gene expression but less apoptosis than that of VAT. All features contribute to the morbidity associated with increased VAT. To evaluate the relationship between VAT and components of the metabolic syndrome, 55 non-diabetic women, 11 lean (VAT < 68 cm²) and 44 obese were studied. The obese with VAT within the normal range (VAT ≤ 68 cm²) had higher BMI, WHR, BP and resistance to FFA suppression during oGTT in comparison to the lean controls. The obese with VAT > 68 cm² compared to those with VAT ≤ 68 cm² had similar body mass index (BMI) but significantly higher in vivo homeostasis model assessment for insulin resistance (HOMA_IR) results and triglycerides. By pooling all data, correlation analysis indicated that VAT contributes more to insulin resistance (HOMA_IR) than SAT does, but not when insulin-suppressed plasma free fatty acids during oral glucose tolerance test as an index of insulin resistance are taken into consideration.

Key words

Adipose Tissue - Subcutaneous (SAT) - Visceral (VAT) - Obesity - Metabolic Syndrome - Insulin Resistance

Full Text

References

1 Wajchenberg B L. Subcutaneous and visceral adipose tissue: Their relation to the metabolic syndrome. Endocr Rev. 2000; 21 697-738
2 Alberti K GMM, Zimmet P Z (for the WHO Consultation). Definition, diagnosis and classification of diabetes mellitus and its complications. Part I: Diagnosis and classification of diabetes mellitus, provisional report of a WHO consultation. Diabet Med. 1998; 15 539-553
3 Montague C T, O’Rahilly S. The perils of portliness. Causes and consequences of visceral adiposity. Ann Rev Diabetes. 2001; 49 1-8
4 Smith S R, Lovejoy J C, Greenway F, Ryan D, deJonge L, de la Bretonne J, Volafova J, Bray G A. Contribution of total body fat, abdominal subcutaneous adipose tissue compartments, and visceral adipose tissue to the metabolic complications of obesity. Metabolism. 2001; 50 426-435
5 Tchkonia T, Karagiannides I, Forse R A, Kirkland J L. Different fat depots are distinct mini-organs. Current Opin Endocrinol Diabetes. 2001; 8 227- 234
6 Smith S R, Zachwieja J J. Visceral adipose tissue: a critical review of intervention strategies. Int J Obes. 1999; 23 329-335
7 Engfeldt P, Arner P. Lipolysis in human adipocytes. Effects of cell size, age and of regional differences. Horm Metab Res Suppl.. 1988; 19 26-29
8 Martin M L, Jensen M D. Effects of body fat distribution on regional lipolysis in obesity. J Clin Invest. 1991; 88 609-613
9 Guo Z, Hensrud D D, Johnson C M, Jensen M D. Regional postprandial fatty acid metabolism in different obesity phenotypes. Diabetes. 1999; 48 1586-1592.
10 Frayn K N. Visceral fat and insulin resistance - causative or correlative?. Brit J Nutrit. 2000; 83 Suppl. 1 S71-S77
11 Lewis G F, Carpentier A, Adeli K, Giacca A. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev. 2002; 23 201-229
12 Rebuffé-Scrieve M, Bronnegard M, Nilsson A, Eldh J, Gustafsson J-A, Björntorp P. Steroid hormone receptors in human adipose tissue. J Clin Endocrinol Metab. 1990; 71 1215-1219
13 Fried S K, Russell C D, Grauso N L, Brolin R E. Lipoprotein lipase regulation by insulin and glucocorticoids in subcutaneous and omental adipose tissues of obese women and men. J Clin Invest. 1993; 92 2191-2198
14 Bujalska I J, Kumar S, Stewart P M. Does central obesity reflect “Cushing’s disease of the omentum“?. Lancet. 1997; 349 1210-1213.
15 Elmquist J K. CNS regulation of energy balance and body weight: insights from rodent models. Lab Anim Sci. 1998; 48 630-637
16 Ahima R S, Flier J S. Adipose tissue as an endocrine organ. Trends Endocr Metab. 2000; 11 327-332
17 Monokoshi Y, Kim Y B, Peroni O D, Fryer L G, Muller C, Carling D, Kahn B B. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature. 2002; 415 339-343
18 Kamon J, Yamauchi T, Waki H, Uchida S K, Ito Y, Suzuki R, Aoyama M, Takasawa K, Kubota N, Terauchi Y, Tobe K, Kadowaki T. Mechanism for the regulation of adiponectin expression. Diabetes. 2002; 51 (Suppl. 2) A351
19 Yang W-S, Jeng C-Y, Wu T-J, Tanaka S, Funahashi T, Matsuzawa Y, Wang J-P, Chen C-H, Tay T-Y, Chuang L-M. Synthetic peroxysome proliferator activated receptor-γ agonist, rosiglitazone, increases plasma levels of adiponectin in type 2 diabetic patients. Diabetes Care:. 2002; 25 376-380
20 Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley R E, Tataranni P A. Hipoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001; 86 1930-1935.
21 Ito Y, Yamauchi T, Waki H, Kamon J, Uchida S, Kimura S, Kadowaki T. Direct effects of adiponectin on skeletal muscle. Diabetes. 2002; 51 Suppl. 2 A1868
22 Yamauchi T, Kamon J, Terauchi Y, Kubota N, Waki H, Mori Y, Hara K, Akanuma Y, Kimura S, Tobe K, Yoda M, Tomita M, Froguel P, Kadowaki T. Replenishment of fat-derived hormone adiponectin reverses insulin resistance in lipoatrophic diabetes and type 2 diabetes. Diabetes. 2001; 50 Suppl. 2 A282
23 Steppan C M, Bailey S T, Bhat S, Brown E J, Banerjee R R, Wright C M, Patel H R, Ahima R S, Lazar M A. The hormone resistin links obesity to diabetes. Nature. 2001; 409 307-312
24 McTernan P G, McTernan C L, Chetty R, Jenner K, Fisher F M, Lauer M N, Crocker J, Barnett A H, Kumar S. Increased resistin gene and protein expression in human abdominal adipose tissue. J Clin Endocrinol Metab. 2002; 87 2407-2410
25 Engeli S, Sharma A M. Role of adipose tissue for cardiovascular-renal regulation in health and disease. Horm Metab Res. 2000; 32 485-499
26 Yudkin J S, Kumari M, Humphries S E, Mohamed-Ali V. Inflammation, obesity, stress and coronary heart disease; is interleukin-6 the link?. Atherosclerosis. 2000; 148 209-214
27 Päth G, Bornstein S R, Ehrhart-Bornstein M, Scherbaum W A. Interleukin-6 and the interleukin-6 receptor in the human adrenal gland: expression and effects on steroidogenesis. J Clin Endocrinol Metab. 1997; 82 2343-2349
28 Sethi J, Hotamisligil G S. The role of TNFα in adipocyte metabolism. Semin Cell Dev Biol. 1999; 10 19-29
29 Alessi M C, Peiretti F, Morange P, Henry M, Nalbone G, Juhan-Vague I. Production of Plasminogen activator inhibitor-1 by human adipose tissue. Possible link between visceral fat accumulation and vascular disease. Diabetes. 1997; 46 860-867
30 Niesler C U, Siddle K, Prins J B. Human preadipocytes display lower depot-specific susceptibility to apoptosis. Diabetes. 1998; 47 1365-1368
31 Caserta F, Tchkonia T, Civelek V N, Prentki M, Brown N F, McGarry J D, Forse R A, Corkey B E, Hamilton J A, Kirkland J L. Fat depot origin affects fatty acid handling in cultured rat and human preadipocytes. Am J Physiol Endocrinol Metab. 2001; 280 E238-E247
32 Tchkonia T, Giorgadze N, Pirtskhalava T, Tchoukalova Y, Karagiannides I, Forse R A, DePonte M, Stevenson M, Guo W, Han J, Waloga G, Lash T L, Jensen M D, Kirkland J L. Fat depot origin affects adipogenesis in primary cultured and cloned human preadipoocytes. Am J Physiol Regul Integr Comp Physiol. 2002; 82 1286-1296
33 Adams M, Montague C T, Prins J B, Holder J C, Smith S A, Sanders L, Sewter C P, Digby J E, Lazar M E, Chatterjee V KK, O’Rahilly S. Activators of PPARγ have depot-specific effects on human pre-adipocyte differentiation. J Clin Invest. 1997; 100 3149-3153
34 Kelly I, Han T, Walsh K, Lean M. Effects of thiazolidinedione compound on body fat and fat distribution of patients with type 2 diabetes. Diabetes Care. 1999; 22 288-293
35 Ruderman N, Chisholm D, Pi-Sunyer X, Schneider S. The metabolically obese, normal-weight individual revisited. Diabetes. 1998; 47 699-713
36 Rönnemaa T, Koskenvuo M, Marniemi J, Koivunen T, Sajantila A, Rissanen A, Kaitsaari M, Bouchard C, Kaprio J. Glucose metabolism in identical twins discordant for obesity. The critical role of visceral fat. J Clin Endocrinol Metab. 1997; 82 383-387
37 Lemieux S, Prud’homme D, Nadeau A, Tremblay A, Bouchard C, Desprès J P. Seven-year changes in body fat and visceral adipose tissue in women. Diabetes Care. 1996; 19 983-991
38 Marks S J, Moore N R, Clark M I, Strauss B JG, Hockaday T DR. Reduction of visceral adipose tissue and improvement of metabolic indices: effect of dexfenfluramine in NIDDM. Obes Res. 1996; 4 1-7
39 Kelley D E, Williams K V, Price J C, McKolanis T M, Goodpaster B H, Thaete F L. Plasma fatty acids, adiposity, and variance of skeletal muscle insulin resistance in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2001; 86 5412-5419
40 Abate B, Garg A, Peshock R M, Stray-Gundersen J, Grundy S M. Relationships of generalized and regional adiposity to insulin sensitivity in men. J Clin Invest. 1995; 96 88-98
41 Goodpaster B H, Thaete F L, Simoneau J-A, Kelley D E. Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat. Diabetes. 1997; 46 1579-1585

B. L. Wajchenberg

Endocrine Service (Diabetes), Medical Investigation Laboratories

Hospital das Clinicas · São Paulo, SP · Brazil