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Obesity Surgery

, Volume 19, Issue 11, pp 1564–1573 | Cite as

Differential Intra-abdominal Adipose Tissue Profiling in Obese, Insulin-resistant Women

  • Alice Liu
  • Tracey McLaughlin
  • Teresa Liu
  • Arthur Sherman
  • Gail Yee
  • Fahim Abbasi
  • Cindy Lamendola
  • John Morton
  • Samuel W. Cushman
  • Gerald M. Reaven
  • Philip S. Tsao
Clinical Research

Abstract

Background

We recently identified differences in abdominal subcutaneous adipose tissue (SAT) from insulin-resistant (IR) as compared to obesity-matched insulin sensitive individuals, including accumulation of small adipose cells, decreased expression of cell differentiation markers, and increased inflammatory activity. This study was initiated to see if these changes in SAT of IR individuals were present in omental visceral adipose tissue (VAT); in this instance, individuals were chosen to be IR but varied in degree of adiposity. We compared cell size distribution and genetic markers in SAT and VAT of IR individuals undergoing bariatric surgery.

Methods

Eleven obese/morbidly obese women were IR by the insulin suppression test. Adipose tissue surgical samples were fixed in osmium tetroxide for cell size analysis via Beckman Coulter Multisizer. Quantitative real-time polymerase chain reaction for genes related to adipocyte differentiation and inflammation was performed.

Results

While proportion of small cells and expression of adipocyte differentiation genes did not differ between depots, inflammatory genes were upregulated in VAT. Diameter of SAT large cells correlated highly with increasing proportion of small cells in both SAT and VAT (r = 0.85, p = 0.001; r = 0.72, p = 0.01, respectively). No associations were observed between VAT large cells and cell size variables in either depot. The effect of body mass index (BMI) on any variables in both depots was negligible.

Conclusions

The major differential property of VAT of IR women is increased inflammatory activity, independent of BMI. The association of SAT adipocyte hypertrophy with hyperplasia in both depots suggests a primary role SAT may have in regulating regional fat storage.

Keywords

Adipose cell size Inflammation Obesity Visceral adipose tissue 

Notes

Acknowledgments

Funding for this study was provided by study grants NIH/NIDDK 1 R01 DK071309-01, 5 R01 DK071333-04, and 5 F32 DK079578-02, by the NIDDK Intramural Research Program and supported by Human Health Service grant M01-RR00070.

Conflict of interest

The authors disclose that there was no commercial interest involved in the study.

References

  1. 1.
    Olefsky J, Reaven GM, Farquhar JW. Effects of weight reduction on obesity. Studies of lipid and carbohydrate metabolism in normal and hyperlipoproteinemic subjects. J Clin Invest. 1974;53:64–76.CrossRefGoogle Scholar
  2. 2.
    Ferrannini E, Natali A, Bell P, et al. Insulin resistance and hypersecretion in obesity. European Group for the Study of Insulin Resistance (EGIR). J Clin Invest. 1997;100:1166–73.CrossRefGoogle Scholar
  3. 3.
    Abbasi F, Brown BW, Lamendola C, et al. Relationship between obesity, insulin resistance, and coronary heart disease risk. J Am Coll Cardiol. 2002;40:937–43.CrossRefGoogle Scholar
  4. 4.
    McLaughlin T, Abbasi F, Lamendola C, et al. Heterogeneity in the prevalence of risk factors for cardiovascular disease and type 2 diabetes mellitus in obese individuals: effect of differences in insulin sensitivity. Arch Intern Med. 2007;167:642–8.CrossRefGoogle Scholar
  5. 5.
    McLaughlin T, Sherman A, Tsao P, et al. Enhanced proportion of small adipose cells in insulin-resistant vs insulin-sensitive obese individuals implicates impaired adipogenesis. Diabetologia. 2007;50:1707–15.CrossRefGoogle Scholar
  6. 6.
    McLaughlin T, Deng A, Gonzales O, et al. Insulin resistance is associated with a modest increase in inflammation in subcutaneous adipose tissue of moderately obese women. Diabetologia. 2008;51:2303–8.CrossRefGoogle Scholar
  7. 7.
    Montague CT, O’Rahilly S. The perils of portliness: causes and consequences of visceral adiposity. Diabetes. 2000;49:883–8.CrossRefGoogle Scholar
  8. 8.
    Pouliot MC, Despres JP, Nadeau A, et al. Visceral obesity in men. Associations with glucose tolerance, plasma insulin, and lipoprotein levels. Diabetes. 1992;41:826–34.CrossRefGoogle Scholar
  9. 9.
    Pei D, Jones CN, Bhargava R, et al. Evaluation of octreotide to assess insulin-mediated glucose disposal by the insulin suppression test. Diabetologia. 1994;37:843–5.CrossRefGoogle Scholar
  10. 10.
    Greenfield M, Doberne L, Kraemer F, et al. Assessment of insulin resistance with the insulin suppression test and the euglycemic clamp. Diabetes. 1981;30:387–92.CrossRefGoogle Scholar
  11. 11.
    Shen SW, Reaven GM, Farquhar JW. Comparison of impedance to insulin-mediated glucose uptake in normal subjects and in subjects with latent diabetes. J Clin Invest. 1970;49:2151–60.CrossRefGoogle Scholar
  12. 12.
    Livingston EH, Lee S. Body surface area prediction in normal-weight and obese patients. Am J Physiol Endocrinol Metab. 2001;281:E586–91.CrossRefGoogle Scholar
  13. 13.
    Yip J, Facchini FS, Reaven GM. Resistance to insulin-mediated glucose disposal as a predictor of cardiovascular disease. J Clin Endocrinol Metab. 1998;83:2773–6.CrossRefGoogle Scholar
  14. 14.
    Facchini FS, Hua N, Abbasi F, et al. Insulin resistance as a predictor of age-related diseases. J Clin Endocrinol Metab. 2001;86:3574–8.CrossRefGoogle Scholar
  15. 15.
    Carantoni M, Abbasi F, Chu L, et al. Adherence of mononuclear cells to endothelium in vitro is increased in patients with NIDDM. Diabetes Care. 1997;20:1462–5.CrossRefGoogle Scholar
  16. 16.
    Hirsch J, Knittle JL. Cellularity of obese and nonobese human adipose tissue. Fed Proc. 1970;29:1516–21.PubMedGoogle Scholar
  17. 17.
    Cinti S, Mitchell G, Barbatelli G, et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res. 2005;46:2347–55.CrossRefGoogle Scholar
  18. 18.
    Edens NK, Fried SK, Kral JG, et al. In vitro lipid synthesis in human adipose tissue from three abdominal sites. Am J Physiol Endocrinol Metab. 1993;265:374–9.CrossRefGoogle Scholar
  19. 19.
    Rebuffe-Scrive M, Anderson B, Olbe L, et al. Metabolism of adipose tissue in intraabdominal depots in severely obese men and women. Metabolism. 1990;39:1021–5.CrossRefGoogle Scholar
  20. 20.
    Tchernof A, Belanger C, Morisset AS, et al. Regional differences in adipose tissue metabolism in women: minor effect of obesity and body fat distribution. Diabetes. 2006;55:1353–60.CrossRefGoogle Scholar
  21. 21.
    Drolet R, Richard C, Sniderman A, et al. Hypertrophy and hyperplasia of abdominal adipose tissues in women. Int J Obes. 2008;32:283–91.CrossRefGoogle Scholar
  22. 22.
    Kashiwagi A, Mott D, Bogardus C, et al. The effects of short-term overfeeding on adipocyte metabolism in Pima Indians. Metabolism. 1985;34:364–70.CrossRefGoogle Scholar
  23. 23.
    Faust IM, Johnson PR, Stern JS, et al. Diet-induced adipocyte number increase in adult rats: a new model of obesity. Am J Physiol. 1978;235:E279–86.PubMedGoogle Scholar
  24. 24.
    Tchkonia T, Tchoukalova Y, Giorgadze N, et al. Abundance of two human preadipocyte subtypes with distinct capacities for replication, adipogenesis, and apoptosis varies among fat depots. Am J Physiol Endocrinol Metab. 2005;288:E267–77.CrossRefGoogle Scholar
  25. 25.
    Bruun JM, Lihn AS, Madan AK, et al. Higher production of IL-8 in visceral vs. subcutaneous adipose tissue. Implication of nonadipose cells in adipose tissue. Am J Physiol Endocrinol Metab. 2004;286:8–13.CrossRefGoogle Scholar
  26. 26.
    Bruun JM, Lihn AS, Pedersen SB, et al. Monocyte chemoattractant protein-1 release is higher in visceral than subcutaneous human adipose tissue (AT): implication of macrophages resident in the AT. J Clin Endocrinol Metab. 2005;90:2282–9.CrossRefGoogle Scholar
  27. 27.
    Fain JN, Madan AK, Hiler ML, et al. 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;145:2273–82.CrossRefGoogle Scholar
  28. 28.
    Fried SK, Bunkin DA, Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab. 1998;83:847–50.PubMedGoogle Scholar
  29. 29.
    Vohl MC, Sladek R, Robitaille J, et al. A survey of genes differentially expressed in subcutaneous and visceral adipose tissue in men. Obes Res. 2004;12:1217–22.CrossRefGoogle Scholar
  30. 30.
    Jia SH, Li Y, Parodo J, et al. Pre–B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis. J Clin Invest. 2004;113:1318–27.CrossRefGoogle Scholar
  31. 31.
    Moschen AR, Kaser A, Enrich B, et al. Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol. 2007;178:1748–58.CrossRefGoogle Scholar
  32. 32.
    Oki K, Yamane K, Kamei N, et al. Circulating visfatin level is correlated with inflammation, but not with insulin resistance. Clin Endocrinol (Oxf). 2007;67:796–800.CrossRefGoogle Scholar
  33. 33.
    Pagano C, Pilon C, Olivieri M, et al. Reduced plasma visfatin/pre-B cell colony-enhancing factor in obesity is not related to insulin resistance in humans. J Clin Endocrinol Metab. 2006;91:3165–70.CrossRefGoogle Scholar
  34. 34.
    van der Veer E, Nong Z, O’Neil C, et al. Pre-B-cell colony-enhancing factor regulates NAD+-dependent protein deacetylase activity and promotes vascular smooth muscle cell maturation. Circ Res. 2005;97:25–34.CrossRefGoogle Scholar
  35. 35.
    Varma V, Yao-Borengasser A, Rasouli N, et al. Human visfatin expression: relationship to insulin sensitivity, intramyocellular lipids, and inflammation. J Clin Endocrinol Metab. 2007;92:666–72.CrossRefGoogle Scholar
  36. 36.
    Montague CT, Prins JB, Sanders L, et al. Depot- and sex-specific differences in human leptin mRNA expression: implications for the control of regional fat distribution. Diabetes. 1997;46:342–7.CrossRefGoogle Scholar
  37. 37.
    Van Harmelen V, Reynisdottir S, Eriksson P, et al. Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes. 1998;47:913–7.CrossRefGoogle Scholar
  38. 38.
    Weisberg SP, McCann D, Desai M, et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112:1796–808.CrossRefGoogle Scholar
  39. 39.
    Xu H, Barnes GT, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112:1821–30.CrossRefGoogle Scholar
  40. 40.
    Weisberg SP, Hunter D, Huber R, et al. CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest. 2006;116:115–24.CrossRefGoogle Scholar
  41. 41.
    Murano I, Barbatelli G, Parisani V, et al. Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice. J Lipid Res. 2008;49:1562–8.CrossRefGoogle Scholar
  42. 42.
    Boivin A, Brochu G, Marceau S, et al. Regional differences in adipose tissue metabolism in obese men. Metabolism. 2007;56:533–40.CrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2009

Authors and Affiliations

  • Alice Liu
    • 1
  • Tracey McLaughlin
    • 1
  • Teresa Liu
    • 2
  • Arthur Sherman
    • 2
  • Gail Yee
    • 3
  • Fahim Abbasi
    • 3
  • Cindy Lamendola
    • 3
  • John Morton
    • 4
  • Samuel W. Cushman
    • 2
  • Gerald M. Reaven
    • 3
  • Philip S. Tsao
    • 3
  1. 1.Division of Endocrinology, Department of MedicineStanford University Medical CenterStanfordUSA
  2. 2.National Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaUSA
  3. 3.Division of Cardiology, Department of MedicineStanford UniversityStanfordUSA
  4. 4.Department of SurgeryStanford UniversityStanfordUSA

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