Home LiteratureArticle Details
PMID: 17393135 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Adipose tissue distribution and risk of metabolic disease: does thiazolidinedione-induced adipose tissue redistribution provide a clue to the answer?

Diabetologia ·Vol. 50 ·No. 6 ·2007-06-00 ·Pages 1127-39

Yang X, Smith U

Abstract

The relative effect of visceral and subcutaneous obesity on the risk of chronic metabolic disease has been a matter of long-term dispute. While ample data support either of the fat depots being causative or associative, valid argument for one depot often automatically belittles the other. Paradigms such as the visceral/portal hypothesis and the acquired lipodystrophy/ectopic fat storage and endocrine hypothesis have been proposed. Nevertheless, neither hypothesis alone explains the entire pathophysiological setting. Treatment of diabetes with thiazolidinediones selectively increases fat partitioning to the subcutaneous adipose depot but does not change visceral fat accumulation. This is in contrast to the preferential visceral fat mobilisation by diet and exercise. Surgical removal of visceral or subcutaneous adipose tissue yields relatively long-lasting metabolic improvement only when combined with procedures that ameliorate adipose tissue cell composition. These studies illustrate that human adipose tissue in different anatomic locations does not work in isolation, and that there is a best-fit relationship in terms of volume and function among different fat depots that needs to be met to maintain the systemic energy balance and to prevent the complications related to obesity.

MeSH Terms
Adipose Tissue/anatomy & histology,cytology,physiology Body Weight Hormones/physiology Humans Insulin Resistance Metabolic Diseases/etiology Metabolic Syndrome/prevention & control Overweight/physiology Thiazolidinediones/therapeutic use
Chemicals
Hormones Thiazolidinediones
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Yang X
Centre of Excellence for Metabolic and Cardiovascular Research/The Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
Smith U
References (98)
98 references, click to expand
  1. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase.
    Nat Med. 2002 Nov;8(11):1288-95 PMID: 12368907
  2. Adiponectin acts in the brain to decrease body weight.
    Nat Med. 2004 May;10(5):524-9 PMID: 15077108
  3. Circulating interleukin 6 levels, blood pressure, and insulin sensitivity in apparently healthy men and women.
    J Clin Endocrinol Metab. 2001 Mar;86(3):1154-9 PMID: 11238501
  4. Regional body composition changes exhibit opposing effects on coronary heart disease risk factors.
    Arterioscler Thromb Vasc Biol. 2004 May;24(5):923-9 PMID: 15016639
  5. Exercise training-induced triglyceride lowering negatively correlates with DHEA levels in men with type 2 diabetes.
    Int J Obes Relat Metab Disord. 2001 Aug;25(8):1108-12 PMID: 11477494
  6. Metabolic and body composition factors in subgroups of obesity: what do we know?
    J Clin Endocrinol Metab. 2004 Jun;89(6):2569-75 PMID: 15181025
  7. Heterogeneous distribution of beta and alpha-2 adrenoceptor binding sites in human fat cells from various fat deposits: functional consequences.
    Eur J Clin Invest. 1987 Apr;17(2):156-65 PMID: 3034620
  8. Two-hour insulin determination improves the ability of abdominal fat measurement to identify risk for the metabolic syndrome.
    Diabetes Care. 2003 Jun;26(6):1725-30 PMID: 12766101
  9. Glucose uptake and perfusion in subcutaneous and visceral adipose tissue during insulin stimulation in nonobese and obese humans.
    J Clin Endocrinol Metab. 2002 Aug;87(8):3902-10 PMID: 12161530
  10. Intrinsic regional differences in androgen receptors and dihydrotestosterone metabolism in human preadipocytes.
    Horm Metab Res. 2002 May;34(5):223-8 PMID: 12063633
  11. Adipose depot-specific expression of cIAP2 in human preadipocytes and modulation of expression by serum factors and TNFalpha.
    Int J Obes Relat Metab Disord. 2001 Jul;25(7):1027-33 PMID: 11443502
  12. The impact of liposuction on body fat.
    Plast Reconstr Surg. 1998 Oct;102(5):1686-9 PMID: 9774031
  13. Association of visceral fat with coronary risk factors in a population-based sample of postmenopausal women.
    Int J Obes Relat Metab Disord. 2002 Jan;26(1):33-9 PMID: 11791144
  14. Human adipose triglyceride lipase (PNPLA2) is not regulated by obesity and exhibits low in vitro triglyceride hydrolase activity.
    Diabetologia. 2006 Jul;49(7):1629-36 PMID: 16752181
  15. Comparison of hormone-sensitive lipase activity in visceral and subcutaneous human adipose tissue.
    J Clin Endocrinol Metab. 1997 Dec;82(12):4162-6 PMID: 9398732
  16. Rosiglitazone promotes development of a novel adipocyte population from bone marrow-derived circulating progenitor cells.
    J Clin Invest. 2006 Dec;116(12 ):3220-8 PMID: 17143331
  17. Depot- and sex-specific differences in human leptin mRNA expression: implications for the control of regional fat distribution.
    Diabetes. 1997 Mar;46(3):342-7 PMID: 9032087
  18. Are there persons who are obese, but metabolically healthy?
    Metabolism. 2001 Dec;50(12):1499-504 PMID: 11735101
  19. Omental and subcutaneous adipose tissue steroid levels in obese men.
    Steroids. 2006 Aug;71(8):674-82 PMID: 16762384
  20. Glucose uptake and insulin action in human adipose tissue--influence of BMI, anatomical depot and body fat distribution.
    Int J Obes Relat Metab Disord. 2002 Jan;26(1):17-23 PMID: 11791142
  21. Effects of troglitazone on fat distribution in the treatment of male type 2 diabetes.
    Metabolism. 1999 Sep;48(9):1102-7 PMID: 10484048
  22. Activators of peroxisome proliferator-activated receptor gamma have depot-specific effects on human preadipocyte differentiation.
    J Clin Invest. 1997 Dec 15;100(12):3149-53 PMID: 9399962
  23. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery.
    N Engl J Med. 2004 Dec 23;351(26):2683-93 PMID: 15616203
  24. Differential regulation of adiponectin secretion from cultured human omental and subcutaneous adipocytes: effects of insulin and rosiglitazone.
    J Clin Endocrinol Metab. 2002 Dec;87(12):5662-7 PMID: 12466369
  25. Does central obesity reflect "Cushing's disease of the omentum"?
    Lancet. 1997 Apr 26;349(9060):1210-3 PMID: 9130942
  26. Deterioration of the metabolic risk profile in women. Respective contributions of impaired glucose tolerance and visceral fat accumulation.
    Diabetes Care. 2001 May;24(5):902-8 PMID: 11347752
  27. The effects of surgically removing subcutaneous fat on the metabolic profile and insulin sensitivity in obese women after large-volume liposuction treatment.
    Horm Metab Res. 2002 Aug;34(8):446-9 PMID: 12198600
  28. Regional uptake of meal fatty acids in humans.
    Am J Physiol Endocrinol Metab. 2003 Dec;285(6):E1282-8 PMID: 12915396
  29. 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 N Y Acad Sci. 2002 Jun;967:363-78 PMID: 12079864
  30. Effects of a thiazolidinedione compound on body fat and fat distribution of patients with type 2 diabetes.
    Diabetes Care. 1999 Feb;22(2):288-93 PMID: 10333947
  31. Analysis of lipolytic protein trafficking and interactions in adipocytes.
    J Biol Chem. 2007 Feb 23;282(8):5726-35 PMID: 17189257
  32. Thiazolidinedione derivative improves fat distribution and multiple risk factors in subjects with visceral fat accumulation--double-blind placebo-controlled trial.
    Diabetes Res Clin Pract. 2001 Dec;54(3):181-90 PMID: 11689273
  33. Intra-abdominal adipose tissue values associated with risk of possessing elevated blood lipids and blood pressure.
    Obes Res. 1994 Nov;2(6):563-8 PMID: 16355516
  34. Understanding adipocyte differentiation.
    Physiol Rev. 1998 Jul;78(3):783-809 PMID: 9674695
  35. Mechanisms for differences in lipolysis between human subcutaneous and omental fat cells.
    J Clin Endocrinol Metab. 1992 Jul;75(1):15-20 PMID: 1320047
  36. Regulation of hepatic acute phase plasma protein genes by hepatocyte stimulating factors and other mediators of inflammation.
    Mol Biol Med. 1990 Apr;7(2):147-59 PMID: 1692952
  37. Metabolism of adipose tissue in intraabdominal depots in severely obese men and women.
    Metabolism. 1990 Oct;39(10):1021-5 PMID: 2215250
  38. Malonyl-CoA, fuel sensing, and insulin resistance.
    Am J Physiol. 1999 Jan;276(1 Pt 1):E1-E18 PMID: 9886945
  39. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase.
    Nature. 2002 Jan 17;415(6869):339-43 PMID: 11797013
  40. Lipoprotein lipase regulation by insulin and glucocorticoid in subcutaneous and omental adipose tissues of obese women and men.
    J Clin Invest. 1993 Nov;92(5):2191-8 PMID: 8227334
  41. Splanchnic lipolysis in human obesity.
    J Clin Invest. 2004 Jun;113(11):1582-8 PMID: 15173884
  42. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome.
    Endocr Rev. 2000 Dec;21(6):697-738 PMID: 11133069
  43. Target value of intraabdominal fat area for improving coronary heart disease risk factors.
    Obes Res. 2004 Apr;12(4):695-703 PMID: 15090639
  44. Contributions of total body fat, abdominal subcutaneous adipose tissue compartments, and visceral adipose tissue to the metabolic complications of obesity.
    Metabolism. 2001 Apr;50(4):425-35 PMID: 11288037
  45. Effect of troglitazone on body fat distribution in type 2 diabetic patients.
    Diabetes Care. 1999 Jun;22(6):908-12 PMID: 10372240
  46. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia.
    J Clin Endocrinol Metab. 2001 May;86(5):1930-5 PMID: 11344187
  47. In vitro lipid synthesis in human adipose tissue from three abdominal sites.
    Am J Physiol. 1993 Sep;265(3 Pt 1):E374-9 PMID: 8214046
  48. Is there a threshold of visceral fat loss that improves the metabolic profile in obese postmenopausal women?
    Metabolism. 2003 May;52(5):599-604 PMID: 12759890
  49. Contribution of intra-abdominal fat accumulation to the impairment of glucose and lipid metabolism in human obesity.
    Metabolism. 1987 Jan;36(1):54-9 PMID: 3796297
  50. Quantification of adipose tissue by MRI: relationship with anthropometric variables.
    J Appl Physiol (1985). 1992 Feb;72(2):787-95 PMID: 1559959
  51. The morphology and metabolism of intraabdominal adipose tissue in men.
    Metabolism. 1992 Nov;41(11):1242-8 PMID: 1435298
  52. Effect of Abdominal Lipectomy on Lipid Profile, Glucose Handling and Blood Pressure in Patients with Truncal Obesity.
    Obes Surg. 1996 Apr;6(2):159-166 PMID: 10729858
  53. Regulation of glucose transport and insulin signaling by troglitazone or metformin in adipose tissue of type 2 diabetic subjects.
    Diabetes. 2002 Jan;51(1):30-6 PMID: 11756319
  54. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid.
    J Clin Endocrinol Metab. 1998 Mar;83(3):847-50 PMID: 9506738
  55. Alpha 2A-adrenergic regulation of cyclic AMP accumulation and lipolysis in human omental and subcutaneous adipocytes.
    Int J Obes Relat Metab Disord. 1996 Feb;20(2):185-9 PMID: 8646256
  56. Glucocorticoids down-regulate glucose uptake capacity and insulin-signaling proteins in omental but not subcutaneous human adipocytes.
    J Clin Endocrinol Metab. 2004 Jun;89(6):2989-97 PMID: 15181089
  57. Daily exercise lowers blood pressure and reduces visceral adipose tissue areas in overweight Japanese men.
    Diabetes Res Clin Pract. 2003 Dec;62(3):149-57 PMID: 14625129
  58. A pilot study of long-term effects of a novel obesity treatment: omentectomy in connection with adjustable gastric banding.
    Int J Obes Relat Metab Disord. 2002 Feb;26(2):193-9 PMID: 11850750
  59. Differences in mRNA expression of the proteins secreted by the adipocytes in human subcutaneous and visceral adipose tissues.
    Biochim Biophys Acta. 2000 Jan 3;1500(1):88-96 PMID: 10564721
  60. Regional adiposity and morbidity.
    Physiol Rev. 1994 Oct;74(4):761-811 PMID: 7938225
  61. Increased lipolysis and decreased leptin production by human omental as compared with subcutaneous preadipocytes.
    Diabetes. 2002 Jul;51(7):2029-36 PMID: 12086930
  62. Decrease in intra-abdominal visceral fat may reduce blood pressure in obese hypertensive women.
    Hypertension. 1996 Jan;27(1):125-9 PMID: 8591874
  63. Cholesterol, a cell size-dependent signal that regulates glucose metabolism and gene expression in adipocytes.
    J Biol Chem. 2001 May 18;276(20):16904-10 PMID: 11278795
  64. Efficacy of troglitazone on body fat distribution in type 2 diabetes.
    Diabetes Care. 2000 Aug;23 (8):1067-71 PMID: 10937499
  65. Effect of pioglitazone on body composition and energy expenditure: a randomized controlled trial.
    Metabolism. 2005 Jan;54(1):24-32 PMID: 15562376
  66. Leptin: its role in obesity and beyond.
    Diabetologia. 1997 Dec;40(12):1371-9 PMID: 9447943
  67. Relationships between visceral, trunk and whole-body adipose tissue weights by cadaver dissection.
    Ann Hum Biol. 2003 Nov-Dec;30(6):668-77 PMID: 14675908
  68. Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts type II diabetes independent of insulin resistance.
    Diabetologia. 2000 Dec;43(12):1498-506 PMID: 11151758
  69. Regional differences in the response of human pre-adipocytes to PPARgamma and RXRalpha agonists.
    Diabetes. 2002 Mar;51(3):718-23 PMID: 11872672
  70. Stromal cells are the main plasminogen activator inhibitor-1-producing cells in human fat: evidence of differences between visceral and subcutaneous deposits.
    Arterioscler Thromb Vasc Biol. 2002 Jan;22(1):173-8 PMID: 11788479
  71. Noradrenaline-induced lipolysis in isolated mesenteric, omental and subcutaneous adipocytes from obese subjects.
    Int J Obes Relat Metab Disord. 1997 Nov;21(11):972-9 PMID: 9368819
  72. Effects of pioglitazone versus diet and exercise on metabolic health and fat distribution in upper body obesity.
    Diabetes Care. 2003 Nov;26(11):3148-52 PMID: 14578253
  73. Visceral adipose tissue: a critical review of intervention strategies.
    Int J Obes Relat Metab Disord. 1999 Apr;23(4):329-35 PMID: 10340808
  74. Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients.
    J Clin Endocrinol Metab. 2002 Jun;87(6):2784-91 PMID: 12050251
  75. Visceral fat as a main determinant of plasminogen activator inhibitor 1 level in women.
    Int J Obes Relat Metab Disord. 1998 Apr;22(4):312-7 PMID: 9578235
  76. Differences at the receptor and postreceptor levels between human omental and subcutaneous adipose tissue in the action of insulin on lipolysis.
    Diabetes. 1983 Feb;32(2):117-23 PMID: 6337893
  77. Expression of cellular inhibitor of apoptosis protein-2 in human subcutaneous and omental adipose tissue.
    Int J Obes Relat Metab Disord. 2004 Mar;28(3):352-6 PMID: 14724658
  78. Risk factors in obese women, with particular reference to visceral fat component.
    Diabetes Metab. 1997 Feb;23 (1):68-74 PMID: 9059769
  79. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans.
    Endocrinology. 2004 May;145(5):2273-82 PMID: 14726444
  80. Comparison of proliferation and differentiation capacity of human adipocyte precursor cells from the omental and subcutaneous adipose tissue depot of obese subjects.
    Metabolism. 2004 May;53(5):632-7 PMID: 15131769
  81. Steroid hormone receptors in human adipose tissues.
    J Clin Endocrinol Metab. 1990 Nov;71(5):1215-9 PMID: 2229280
  82. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase.
    Science. 2004 Nov 19;306(5700):1383-6 PMID: 15550674
  83. Fat depot origin affects adipogenesis in primary cultured and cloned human preadipocytes.
    Am J Physiol Regul Integr Comp Physiol. 2002 May;282(5):R1286-96 PMID: 11959668
  84. The effect of metformin on fat distribution and the metabolic syndrome in women with polycystic ovary syndrome--a randomised, double-blind, placebo-controlled trial.
    BJOG. 2006 Jul;113(7):817-24 PMID: 16827766
  85. Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution.
    J Clin Invest. 1983 Sep;72(3):1150-62 PMID: 6350364
  86. The function of leptin in nutrition, weight, and physiology.
    Nutr Rev. 2002 Oct;60(10 Pt 2):S1-14; discussion S68-84, 85-7 PMID: 12403078
  87. Depot- and gender-related differences in the lipolytic pathway of adipose tissue from severely obese patients.
    Cell Physiol Biochem. 2006;17(3-4):173-80 PMID: 16543734
  88. Lipoatrophy revisited.
    Trends Endocrinol Metab. 2000 Dec;11(10):410-6 PMID: 11091118
  89. Effect of a six month gemfibrozil treatment and dietary recommendations on the metabolic risk profile of visceral obese men.
    Int J Obes Relat Metab Disord. 2001 Aug;25(8):1136-43 PMID: 11477498
  90. Comparison of human abdominal subcutaneous versus omental preadipocyte differentiation in primary culture.
    Metabolism. 2002 Sep;51(9):1211-5 PMID: 12200769
  91. Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease.
    N Engl J Med. 2004 Jun 17;350(25):2549-57 PMID: 15201411
  92. Higher production of IL-8 in visceral vs. subcutaneous adipose tissue. Implication of nonadipose cells in adipose tissue.
    Am J Physiol Endocrinol Metab. 2004 Jan;286(1):E8-13 PMID: 13129857
  93. High local concentrations and effects on differentiation implicate interleukin-6 as a paracrine regulator.
    Obes Res. 2004 Mar;12(3):454-60 PMID: 15044662
  94. Leptin secretion from subcutaneous and visceral adipose tissue in women.
    Diabetes. 1998 Jun;47(6):913-7 PMID: 9604868
  95. Improvements in cardiovascular risk profile with large-volume liposuction: a pilot study.
    Plast Reconstr Surg. 2001 Aug;108(2):510-9; discussion 520-1 PMID: 11496197
  96. Adipose tissue as a buffer for daily lipid flux.
    Diabetologia. 2002 Sep;45(9):1201-10 PMID: 12242452
  97. Intra-abdominal adipose tissue cut-points related to elevated cardiovascular risk in women.
    Int J Obes Relat Metab Disord. 1996 Jul;20(7):613-7 PMID: 8817354
  98. Increased obese mRNA expression in omental fat cells from massively obese humans.
    Nat Med. 1995 Sep;1(9):953-6 PMID: 7585224
Article Info
Journal
Diabetologia
Abbr.
Diabetologia
ISSN
0012-186X
DOI
10.1007/s00125-007-0640-1
Published
2007-06-00
Epub
2007-00-29
Pages
1127-39
Language
English
Region
Germany
NLM ID
0006777
Subset
IM
External Links
PubMed source DOI: 10.1007/s00125-007-0640-1 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2