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

Abstract

Adipose hypoxia and hypoxia-inducible factor 1α (HIF-1α) 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-1α and fibrosis in hypoxic adipose tissue. Curcumin attenuated high-fat diet (HFD) induced adipose hypoxia and HIF-1α 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-1α induction, further indicating that curcumin blocked mTOR/HIF-1α signaling via regulation of AMPK. In conclusion, curcumin prevented adipose hypoxia and decreased HIF-1α-associated adipose fibrosis via suppression of AMPK-mediated mTOR pathway, suggesting that HIF-1α might be a therapeutical target for the prevention of fibrosis in adipose tissue.

Keywords

• Curcumin
• Hypoxia
• HIF-1α
• mTOR
• Fibrosis
• Adipose tissue