Weight Cycling Increases T-cell Accumulation in Adipose Tissue and Impairs Systemic Glucose Tolerance

Overview

Journal Diabetes

Specialty Endocrinology

Date 2013 Jun 5

PMID 23733197

Citations 67

Authors

Emily K Anderson

Dario A Gutierrez

Arion Kennedy

Alyssa H Hasty

Affiliations

Soon will be listed here.

Abstract

Obesity is one of the leading causes of morbidity in the U.S. Accumulation of proinflammatory immune cells in adipose tissue (AT) contributes to the development of obesity-associated disorders. Weight loss is the ideal method to counteract the negative consequences of obesity; however, losses are rarely maintained, leading to bouts of weight cycling. Fluctuations in weight have been associated with worsened metabolic and cardiovascular outcomes; yet, the mechanisms explaining this potential correlation are not known. For determination of whether weight cycling modulates AT immune cell populations, inflammation, and insulin resistance, mice were subjected to a diet-switch protocol designed to induce weight cycling. Weight-cycled mice displayed decreased systemic glucose tolerance and impaired AT insulin sensitivity when compared with mice that gained weight but did not cycle. AT macrophage number and polarization were not modulated by weight cycling. However, weight cycling did increase the number of CD4(+) and CD8(+) T cells in AT. Expression of multiple T helper 1-associated cytokines was also elevated subsequent to weight cycling. Additionally, CD8(+) effector memory T cells were present in AT of both obese and weight-cycled mice. These studies indicate that an exaggerated adaptive immune response in AT may contribute to metabolic dysfunction during weight cycling.

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References

Winer D, Winer S, Shen L, Wadia P, Yantha J, Paltser G . B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med. 2011; 17(5):610-7. PMC: 3270885. DOI: 10.1038/nm.2353. View

Lumeng C, Bodzin J, Saltiel A . Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007; 117(1):175-84. PMC: 1716210. DOI: 10.1172/JCI29881. View

Kosteli A, Sugaru E, Haemmerle G, Martin J, Lei J, Zechner R . Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue. J Clin Invest. 2010; 120(10):3466-79. PMC: 2947229. DOI: 10.1172/JCI42845. View

Gately M, Renzetti L, Magram J, Stern A, Adorini L, Gubler U . The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses. Annu Rev Immunol. 1998; 16:495-521. DOI: 10.1146/annurev.immunol.16.1.495. View

Olson M, Kelsey S, Bittner V, Reis S, Reichek N, Handberg E . Weight cycling and high-density lipoprotein cholesterol in women: evidence of an adverse effect: a report from the NHLBI-sponsored WISE study. Women's Ischemia Syndrome Evaluation Study Group. J Am Coll Cardiol. 2000; 36(5):1565-71. DOI: 10.1016/s0735-1097(00)00901-3. View

Jeffery R, Wing R, French S . Weight cycling and cardiovascular risk factors in obese men and women. Am J Clin Nutr. 1992; 55(3):641-4. DOI: 10.1093/ajcn/55.3.641. View

Blair S, Shaten J, Brownell K, Collins G, Lissner L . Body weight change, all-cause mortality, and cause-specific mortality in the Multiple Risk Factor Intervention Trial. Ann Intern Med. 1993; 119(7 Pt 2):749-57. DOI: 10.7326/0003-4819-119-7_part_2-199310011-00024. View

Zeyda M, Huber J, Prager G, Stulnig T . Inflammation correlates with markers of T-cell subsets including regulatory T cells in adipose tissue from obese patients. Obesity (Silver Spring). 2010; 19(4):743-8. DOI: 10.1038/oby.2010.123. View

Winer S, Chan Y, Paltser G, Truong D, Tsui H, Bahrami J . Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med. 2009; 15(8):921-9. PMC: 3063199. DOI: 10.1038/nm.2001. View

10.

Ohmura K, Ishimori N, Ohmura Y, Tokuhara S, Nozawa A, Horii S . Natural killer T cells are involved in adipose tissues inflammation and glucose intolerance in diet-induced obese mice. Arterioscler Thromb Vasc Biol. 2009; 30(2):193-9. DOI: 10.1161/ATVBAHA.109.198614. View

11.

Duffaut C, Zakaroff-Girard A, Bourlier V, Decaunes P, Maumus M, Chiotasso P . Interplay between human adipocytes and T lymphocytes in obesity: CCL20 as an adipochemokine and T lymphocytes as lipogenic modulators. Arterioscler Thromb Vasc Biol. 2009; 29(10):1608-14. DOI: 10.1161/ATVBAHA.109.192583. View

12.

Strissel K, Defuria J, Shaul M, Bennett G, Greenberg A, Obin M . T-cell recruitment and Th1 polarization in adipose tissue during diet-induced obesity in C57BL/6 mice. Obesity (Silver Spring). 2010; 18(10):1918-25. PMC: 2894258. DOI: 10.1038/oby.2010.1. View

13.

Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A . Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 2009; 15(8):930-9. PMC: 3115752. DOI: 10.1038/nm.2002. View

14.

McGillicuddy F, Chiquoine E, Hinkle C, Kim R, Shah R, Roche H . Interferon gamma attenuates insulin signaling, lipid storage, and differentiation in human adipocytes via activation of the JAK/STAT pathway. J Biol Chem. 2009; 284(46):31936-44. PMC: 2797265. DOI: 10.1074/jbc.M109.061655. View

15.

Lu H, Buison A, Uhley V, Jen K . Long-term weight cycling in female Wistar rats: effects on metabolism. Obes Res. 1995; 3(6):521-30. DOI: 10.1002/j.1550-8528.1995.tb00186.x. View

16.

Kim H, Imbert J, Leonard W . Both integrated and differential regulation of components of the IL-2/IL-2 receptor system. Cytokine Growth Factor Rev. 2006; 17(5):349-66. DOI: 10.1016/j.cytogfr.2006.07.003. View

17.

Hamm P, SHEKELLE R, Stamler J . Large fluctuations in body weight during young adulthood and twenty-five-year risk of coronary death in men. Am J Epidemiol. 1989; 129(2):312-8. DOI: 10.1093/oxfordjournals.aje.a115135. View

18.

Ojdana D, Safiejko K, Lipska A, Radziwon P, Dadan J, Tryniszewska E . Effector and memory CD4+ and CD8+ T cells in the chronic infection process. Folia Histochem Cytobiol. 2009; 46(4):413-7. DOI: 10.2478/v10042-008-0077-5. View

19.

Woodland D, Kohlmeier J . Migration, maintenance and recall of memory T cells in peripheral tissues. Nat Rev Immunol. 2009; 9(3):153-61. DOI: 10.1038/nri2496. View

20.

Kintscher U, Hartge M, Hess K, Foryst-Ludwig A, Clemenz M, Wabitsch M . T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Arterioscler Thromb Vasc Biol. 2008; 28(7):1304-10. DOI: 10.1161/ATVBAHA.108.165100. View