Journal of Atherosclerosis and Thrombosis
Original Article
C-C Chemokine Receptor 2 Inhibitor Improves Diet-Induced Development of Insulin Resistance and Hepatic Steatosis in Mice
Yukinori TamuraMasayuki SugimotoToshinori MurayamaManabu MinamiYuki NishikazeHiroyuki AriyasuTakashi AkamizuToru KitaMasayuki YokodeHidenori Arai
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Volume 17 (2010) Issue 3 Pages 219-228

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Abstract

Aim: Adipose tissue inflammation induced by macrophage infiltration through the MCP-1/CCR2 pathway is considered to play a pivotal role in the development of visceral obesity and insulin resistance. In the present study, therefore, we examined whether pharmacological inhibition of CCR2 is effective against the development of diet-induced metabolic disorders.
Methods: C57BL/6 mice were fed a high fat and sucrose diet with or without propagermanium (CCR2 inhibitor, 5 or 50 mg/kg BW/day) for 12 weeks from 6 weeks of age. Then we analyzed lipid and glucose metabolism and tissue inflammation in the liver and adipose tissues along with serum markers in those mice.
Results and Conclusion: Propagermanium treatment slightly decreased body weight gain and visceral fat accumulation in diet-induced obese (DIO) mice. Further, propagermanium suppressed macrophage accumulation and shifted adipose tissue macrophage polarization from the pro-inflammatory (M1) state to anti-inflammatory (M2) state in DIO mice. Expressions of TNF-α and MCP-1 mRNA in adipose tissue were reduced by propagermanium treatment, indicating that propagermanim suppressed inflammation in adipose tissue. Propagermanium treatment also ameliorated glucose tolerance, insulin sensitivity, and decreased hepatic triglyceride in DIO mice. Thus, propagermanium improved diet-induced obesity and related metabolic disorders, such as insulin resistance and hepatic steatosis by suppressing inflammation in adipose tissue. Our data indicate that inhibition of CCR2 could improve diet-induced metabolic disorders, and that propagermanium may be a beneficial drug for the treatment of metabolic syndrome.

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