Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Proceedings Article
  • Published:

Metabolic heterogeneity of obesity: role of adipose tissue

International Journal of Obesity Supplements volume 2, pages S8–S10 (2012)Cite this article

Subjects

Abstract

Obesity is not synonymous with insulin resistance. Why some but not all individuals develop insulin resistance with weight excess is not clear, but a number of plausible hypotheses with ample support now exist. This article reviews regional fat distribution, inflammation, lipotoxicity/ectopic fat and impaired adipogenesis as leading theories as to why excess body weight has the potential to promote insulin resistance.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Flegal KM, Carroll MD, Ogden CL, Curtin LR . Prevalence and trends in obesity among US adults, 1999–2008. JAMA 2010; 202: 235–241.

    Article  Google Scholar 

  2. Finklestein EA, Trogdon JG, Cohen JW, Dietz W . Annual medical spending attributable to obesity: payer-and service-specific estimates. Health Aff 2009; 28: w822–w831.

    Article  Google Scholar 

  3. McLaughlin T, Allison G, Abbasi F, Lamendola C, Reaven G . Prevalence of insulin resistance and associated cardiovascular risk factors among normal, overweight, and obese individuals. Metabolism 2004; 53: 495–499.

    Article  CAS  PubMed  Google Scholar 

  4. Yeni-Komshian H, Caratoni M, Abbasi F, Reaven GM . Relationship between several surrogate estimates of insulin resistance and quantification of insulin-mediated glucose disposal in 480 healthy nondiabetic volunteers. Diabetes Care 2000; 23: 171–173.

    Article  CAS  PubMed  Google Scholar 

  5. McLaughlin T, Abbasi F, Lamendola C, Reaven G . Heterogeneity in prevalence of risk factors for cardiovascular disease and type 2 diabetes in obese individuals: impact of differences in insulin sensitivity. Archives Int Med 2007; 167: 642–648.

    Article  CAS  Google Scholar 

  6. Yip J, Gacchini FS, Reaven GM . Resistance to insulin-mediated glucose disposal as a predictor of cardiovascular disease. J Clin Endocrinol Metab 1998; 83: 2773–2777.

    Article  CAS  PubMed  Google Scholar 

  7. Facchini FS, Hua N, Abbasi F, Reaven GM . Insulin resistance as a predictor of age-related-diseases. J Clin Endocrinol Metab 2001; 86: 3574–3578.

    Article  CAS  PubMed  Google Scholar 

  8. Zavaroni I, Bonini L, Gasparini P, Barilli AL, Zuccarelli A, Dall’Aglio E et al. Hyperinsulinemia in a normal population as a predictor of non-insulin-dependent diabetes mellitus, hypertension, and coronary heart disease: the Barilla factory revisited. Metabolism 1999; 48: 989–994.

    Article  CAS  PubMed  Google Scholar 

  9. McLaughlin T, Abbasi F, Lamendola C, Liang L, Reaven G, Schaaf P et al. Differentiation between obesity and insulin resistance in the association with C-reactive protein. Circulation 2002; 106: 2908–2912.

    Article  CAS  PubMed  Google Scholar 

  10. McLaughlin T, Stuhlinger M, Lamendola C, Abbasi F, Reaven GM, Tsao PS . Plasma asymmetric dimethylarginine concentrations are elevated in insulin-resistant women and fall with weight loss. J Clin Endocrinol Metab 2006; 91: 1896–1900.

    Article  CAS  PubMed  Google Scholar 

  11. McLaughlin T, Abbasi F, Kim HS, Lamendola C, Schaaf P, Reaven G . Relationship between insulin resistance, weight loss and coronary heart disease risk in obese healthy women. Metabolism 2001; 50: 795–800.

    Article  CAS  PubMed  Google Scholar 

  12. Ohlson LO, Larsson B, Svardsudd K, Welin L, Eriksson H, Wilhelmsen L 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 

  13. Lapidus L, Bengtsson C, Larsson B, Pennert K, Rybo E, Sjostrom 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. Br Med J 1984; 289: 1257–1261.

    Article  CAS  Google Scholar 

  14. McLaughlin T, Lamendola C, Liu A, Abbasi F . Preferential fat deposition in subcutaneous versus visceral depots is associated with insulin sensitivity. J Clin Endocrinol Metab 2011; 96: E1756–E1760.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Brochu M, Starling RD, Tchernof A, Matthews DE, Garcia-Rubi EET . Visceral adipose tissue is an independent correlate of glucose disposal in older obese postmenopausal women. J Clin Endocrinol Metab 2000; 86: 5366–5371.

    Google Scholar 

  16. Ross R, Aru J, Freeman J, Hudson R, Janssen I . Abdominal adiposity and insulin resistance in obese men. Am J Physiol 2002; 282: E657–E663.

    CAS  Google Scholar 

  17. Ross R, Freeman J, Hudson R, Janssen I . Abdominal obesity, muscle composition, and insulin resistance in premenopausal women. J Clin Endocrinol Metab 2002; 87: 5044–5051.

    Article  CAS  PubMed  Google Scholar 

  18. Goodpaster BH, Thaete FL, Simoneau JA, Kelley DE . Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat. Diabetes 1997; 46: 1579–1585.

    Article  CAS  PubMed  Google Scholar 

  19. Abate N, Garg A, Peshock RM, Stray-Gundersen J, Grundy SM . Relationships of generalized and regional adiposity to insulin sensitivity in men. J Clin Invest 1995; 96: 88–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Porter SA, Massaro JM, Hoffmann U, Vasan RS, O’Donnel CJ, Fox CS . Abdominal subcutaneous adipose tissue: a protective fat depot? Diabetes Care 2009; 32: 1068–1075.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Liu A, McLaughlin T, Liu T, Sherman A, Yee G, Abbasi F et al. Differential intra-abdominal adipose tissue profiling in obese, insulin-resistant women. Obes Surg 2009; 19: 1564–1573.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Bolinder 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  CAS  PubMed  Google Scholar 

  23. Fabbrini E, Tamboli RA, Magkos F, Marks-Shulman PA, Eckhauser AW, Richards WO et al. Surgical removal of omental fat does not improve insulin sensitivity and cardiovascular risk factors in obese adults. Gastroenterology 2010; 139: 448–455.

    Article  PubMed  Google Scholar 

  24. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM et al. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001; 286: 327–334.

    Article  CAS  PubMed  Google Scholar 

  25. Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 2005; 46: 2347–2355.

    Article  CAS  PubMed  Google Scholar 

  26. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante Jr AW, Weisberg S et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112: 1796–1808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Yuan M, Konstantopoulos N, Lee J, Hansen L, Li ZW, Karin M et al. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 2001; 293: 1673–1677.

    Article  CAS  PubMed  Google Scholar 

  28. Kanda H, Tateya S, Tamori Y et al. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 2006; 116: 1494–1505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Weisberg SP, Hunter D, Huber R, Lemieux J, Slaymaker S, Vaddi K et al. CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest 2006; 116: 115–124.

    Article  CAS  PubMed  Google Scholar 

  30. McLaughlin T, Deng A, Gonzales O, Aillaud M, Yee G, Lamendola C et al. Comparison of inflammatory markers in subcutaneous adipose tissue obtained from equally obese insulin resistant and insulin sensitive women. Diabetologia 2008; 51: 2303–2308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Goldfine AB, Fonseca V, Jablonski KA, Pyle L, Staten MA, Shoelson SE, TINSAL-T2D (Targeting Inflammation Using Salsalate in Type 2 Diabetes) Study Team. The effects of salsalate on glycemic control in patients with type 2 diabetes: a randomized trial. Ann Intern Med 2010; 152: 346–357.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Koska J, Ortega E, Bunt JC, Gasser A, Impson J, Hanson RL et al. The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study. Diabetologia 2009; 52: 385–393.

    Article  CAS  PubMed  Google Scholar 

  33. McLaughlin T, Yee G, Glassford A, Lamendola C . Use of a two-stage insulin suppression test to assess the relationship between insulin-suppression of lipolysis and insulin-mediated glucose uptake in overweight/obese, nondiabetic women. Metabolism 2011; 60: 1741–1747.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Samuel VT, Petersen KF, Shulman GI . Lipid-induced insulin resistance: unravelling the mechanism. Lancet 2010; 375: 2267–2277.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Boden G . Obesity, insulin resistance and free fatty acids. Curr Opin Endocrinol Diabetes Obes 2001; 18: 139–143.

    Article  CAS  Google Scholar 

  36. McLaughlin T, Abbasi F, Lamendola C, Kim H, Reaven GM . Metabolic changes following sibutramine-assisted weight loss in obese individuals: role of free fatty acids in the insulin resistance of obesity. Metabolism 2001; 50: 819–824.

    Article  CAS  PubMed  Google Scholar 

  37. Miyazaki Y, Glass L, Triplitt C, Matsuda M, Cusi K, Mahankali A et al. Effect of rosiglitazone on glucose and non-esterified fatty acid metabolism in type II diabetic patients. Diabetologia 2001; 44: 2210–2219.

    Article  CAS  PubMed  Google Scholar 

  38. Bajaj M, Baig R, Suraamornkul S, Hardies LJ, Coletta DK, Cline GW et al. Effects of pioglitazone on intramyocellular fat metabolism in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 2010; 95: 1916–1923.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O et al. Dynamics of fat cell turnover in humans. Nature 2008; 453: 783–787.

    Article  CAS  PubMed  Google Scholar 

  40. Faust IM, Johnson PR, Stern JS, Hirsch J . Diet-induced adipocyte number increase in adult rats: a new model of obesity. Am J Physiol 1978; 4: E279–E286.

    Google Scholar 

  41. Kashiwagi A, Mott D, Bogardus C, Lilioja S, Reaven GM, Foley JE . The effects of short-term overfeeding on adipocyte metabolism in Pima Indians. Metabolism 1985; 34: 364–370.

    Article  CAS  PubMed  Google Scholar 

  42. McLaughlin T, Sherman A, Tsao P, Gonzalez O, Yee G et al. Enhanced proportion of small adipose cells in insulin-resistant vs insulin -sensitive obese individuals implicates impaired adipogenesis. Diabetologia 2007; 50: 1707–1715.

    Article  CAS  PubMed  Google Scholar 

  43. Yang X, Jansson P, Nagaev I, Jack MM, Carvalho E, Sunnerhagen KS et al. Evidence of impaired adipogenesis in insulin resistance. Biochem Biohys Res Commun 2004; 317: 1045–1051.

    Article  CAS  Google Scholar 

  44. McLaughlin T, Deng A, Yee G, Lamendola C, Reaven G, Tsao P et al. Inflammation in subcutaneous adipose tissue: relationship to adipose cell size. Diabetologia 2010; 53: 369–377.

    Article  CAS  PubMed  Google Scholar 

  45. Kim JK, Gavrilova O, Chen Y, Reitman ML, Shulman GI . Mechanism of insulin resistance in AZIP/F-1 fatless mice. J Biol Chem 2000; 275: 8456–8460.

    Article  CAS  PubMed  Google Scholar 

  46. Petersen KF, Oral EA, Dufour S, Befroy D, Ariyan C, Yu C et al. Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. J Clin Invest 2002; 109: 1345–1350.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. McLaughlin T, Liu T, Yee G, Abbasi F, Lamendola C, Reaven G et al. Pioglitazone increases the proportion of small cells in human subcutaneous adipose tissue. Obesity 2010; 18: 926–931.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

TM has received grant support from Amylin/Lilly. TM serves as an expert witness for diabetes cases. TM has also received grant support from National Institutes of Health/National Institute of Digestive Diseases and Diabetes, R01 DK080436, R01DK071309. The author acknowledges Dr Samuel W Cushman for his mentoring. Publication of this supplement was partially supported by Nutrilite Health Institute with an unrestricted educational contribution to Stanford Prevention Research Center.

Author information

Authors and Affiliations

  1. Division of Endocrinology, Stanford University School of Medicine, Stanford, CA, USA

    T McLaughlin

Authors
  1. T McLaughlin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T McLaughlin.

Ethics declarations

Competing interests

The author declares no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

McLaughlin, T. Metabolic heterogeneity of obesity: role of adipose tissue. Int J Obes Supp 2 (Suppl 1), S8–S10 (2012). https://doi.org/10.1038/ijosup.2012.3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijosup.2012.3

Keywords

This article is cited by

Search

Advanced search

Quick links