8-Hydroxy-2-deoxyguanosine ameliorates high-fat diet-induced insulin resistance and adipocyte dysfunction in mice

Joo Young Huh, Inji Jung, Lingjuan Piao, Hunjoo Ha, Myung Hee Chung

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)890-896
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume491
Issue number4
DOIs
StatePublished - 30 Sep 2017

Bibliographical note

Funding Information:
This work was financially supported by the National Research Foundation (NRF) of Korea (No. 2016R1A2B4006575 and 2015R1C1A1A02037367).

Publisher Copyright:
© 2017 Elsevier Inc.

Keywords

  • 8-Hydroxy-2-deoxyguanosine
  • Adipocyte metabolism
  • Insulin resistance
  • Obesity

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