8-Hydroxy-2-deoxyguanosine ameliorates high-fat diet-induced insulin resistance and adipocyte dysfunction in mice
- 주제(키워드) 8-Hydroxy-2-deoxyguanosine , Adipocyte metabolism , Insulin resistance , Obesity
- 등재 SCIE, SCOPUS
- 발행기관 Elsevier B.V.
- 발행년도 2017
- URI http://www.dcollection.net/handler/ewha/000000146949
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.bbrc.2017.07.132
초록/요약
8-Hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, has been recently shown to exert anti-inflammatory effects through inhibition of Rac1. Inflammation in adipose tissue is a hallmark of obesity-induced insulin resistance, but the therapeutic potential of 8-OHdG in treatment of metabolic diseases has not been fully elucidated. The aim of this study was to examine the effect of exogenously administered 8-OHdG on adipose tissue and whole body metabolism. In cultured adipocytes, 8-OHdG inhibited adipogenesis and reversed TNFα-induced insulin resistance. In high-fat diet (HFD)-induced obese mice, 8-OHdG administration blunted the rise in body weight and fat mass. The decrease in adipose tissue mass by 8-OHdG was due to reduced adipocyte hypertrophy through induction of adipose triglyceride lipase and inhibition of fatty acid synthase expression. 8-OHdG also inhibited the infiltration of macrophages, resulting in amelioration of adipose tissue inflammation and adipokine dysregulation. Moreover, 8-OHdG administration ameliorated adipocyte as well as systemic insulin sensitivity. Both in vivo and in vitro results showed that 8-OHdG induces AMPK activation and reduces JNK activation in adipocytes. In conclusion, our results show that orally administered 8-OHdG protects against HFD-induced metabolic disorders by regulating adipocyte metabolism. © 2017 Elsevier Inc.
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