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Am J Physiol Endocrinol Metab (June 24, 2008). doi:10.1152/ajpendo.00309.2007
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Submitted on May 18, 2007
Accepted on June 17, 2008

Voluntary Exercise Improves Insulin Sensitivity and Adipose Tissue Inflammation in Diet-Induced Obese Mice

Richard L Bradley1, Justin Y Jeon2, Fen-Fen Liu1, and Eleftheria Maratos-Flier1*

1 Endocrinology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
2 Sport and Leisure Studies, Yonsei University, Korea, Democratic People's Republic of

* To whom correspondence should be addressed. E-mail: emaratos{at}bidmc.harvard.edu.

Exercise promotes weight loss and improves insulin sensitivity. However, the molecular mechanisms mediating its beneficial effects are not fully understood. Obesity correlates with increased production of inflammatory cytokines, which in turn, contributes to systemic insulin resistance. To test the hypothesis that exercise mitigates this inflammatory response, thereby improving insulin sensitivity, we developed a model of voluntary exercise in mice made obese by feeding of a high fat/high sucrose diet (HFD). Over four weeks, mice fed chow gained 2.3 ± 0.3 g, while HFD mice gained 6.8 ± 0.5 g. After 4 weeks, mice were subdivided into four groups: chow-no exercise, chow-exercise, HFD-no exercise, HFD-exercise and monitored for an additional 6 weeks. Chow-no exercise and HFD-no exercise mice gained an additional 1.2 ± 0.3 g and 3.3 ± 0.5 g respectively. Exercising mice had higher food consumption, but did not gain additional weight. As expected, GTT and ITT showed impaired glucose tolerance and insulin resistance in HFD-no exercise mice. However, glucose tolerance improved significantly and insulin sensitivity was completely normalized in HFD-exercise animals. Furthermore, expression of TNF-{alpha}, MCP-1, PAI-1 and IKK{beta} was increased in adipose tissue from HFD mice compared to chow mice, whereas exercise reversed the increased expression of these inflammatory cytokines. In contrast, expression of these cytokines in liver was unchanged among the four groups. These results suggest that exercise partially reduces adiposity, reverses insulin resistance and decreases adipose tissue inflammation in diet-induced obese mice, despite continued consumption of HFD.




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