Docosahexaenoic acid attenuates adipose tissue angiogenesis and insulin resistance in high fat diet-fed middle-aged mice via a sirt1-dependent mechanism.

ABSTRACT

SCOPE Docosahexaenoic acid (DHA; C22 6, n-3), one of PUFAs, exerts beneficial effects on inflammatory diseases, obesity and diabetes. Angiogenesis in adipose tissue has a major role in the development of obesity and its related metabolic complications. Inhibition of angiogenesis is an emerging strategy for the novel treatment for obesity. Thus, we examined the effect of DHA on angiogenesis in adipose tissues and investigated the underlying mechanisms. METHODS AND RESULTS: In high-fat diet (HFD) fed middle-aged mice, DHA inhibited the macrophage-derived inflammation and angiogenesis in adipose tissues, reduced adipocyte size and body fat composition and improved insulin sensitivity. Moreover, DHA reversed the HFD-induced reduction of Sirt1 in adipose tissues. Interestingly, the effects of DHA were attenuated by lentivirus-mediated Sirt1 knockdown with increasing expression of markers of macrophage-derived inflammation and angiogenesis, associated with impaired insulin sensitivity. CONCLUSION: Overall, our findings demonstrated that DHA reduced angiogenesis of adipose tissues and attenuated insulin resistance in HFD-induced obese mice via the activation of Sirt1.