The role of curcumin in disruption of HIF-1α accumulation to alleviate adipose fibrosis via AMPK-mediated mTOR pathway in high-fat diet fed mice

Adipose hypoxia and hypoxia-inducible factor 1 alpha (HIF-1 alpha) accumulation are tightly associated with adipose dysfunction. Curcumin is a polyphenol with positive effects on inflammation and fibrosis. This study aims to investigate the effects of curcumin on HIF-1 alpha and fibrosis in hypoxic adipose tissue. Curcumin attenuated high-fat diet (HFD) induced adipose hypoxia and HIF-1 alpha, overexpression. Moreover, curcumin effectively reduced inflammatory cytokine and extracellular matrix deposition in adipose tissue, demonstrating its inhibitory effects on adipose inflammation and fibrosis. Curcumin increased AMP-activated protein kinase (AMPK) phosphorylation and suppressed mammalian target of rapamycin (mTOR) activation, while knockdown of AMPK diminished the suppressive effects on mTOR activation and HIF-1 alpha induction, further indicating that curcumin blocked mTOR/HIF-1 alpha signaling via regulation of AMPK. In conclusion, curcumin prevented adipose hypoxia and decreased HIF-1 alpha-associated adipose fibrosis via suppression of AMPK-mediated mTOR pathway, suggesting that HIF-1 alpha might be a therapeutical target for the prevention of fibrosis in adipose tissue. (C) 2017 Elsevier Ltd. All rights reserved.