Nobiletin Attenuates High Glucose‐induced Lipid Accumulation in HepG2 Hepatocytes through Activation of AMP‐activated Protein Kinase‐dependent Signaling

Abstract

Nobiletin, a citrus polymethoxyflavonoid with six methoxy groups, is found abundantly in the peels of citrus fruits. Although nobiletin has been reported to display anti‐inflammatory, anti‐tumor, and anti‐diabetes activities, its effect on lipid modulation remained unclear. In the present study, we investigated the effect of nobiletin on hepatic lipogenesis in high glucose‐induced HepG2 cells. HepG2 cells were incubated in either normal (5.5 mmol/L) or high (25 mmol/L) glucose and subsequently treated with different concentrations of nobiletin (5, 25 and 50 μM). The results revealed that nobiletin markedly inhibited hepatic lipid accumulation in HepG2 cells. Nobiletin also reduced the expression of lipogenic factors, including sterol regulatory element‐binding protein 1c (SREBP‐1c) and fatty acid synthase (FAS). Moreover, nobiletin significantly increased AMP‐activated protein kinase (AMPK) phosphorylation and acetyl‐CoA carboxylase (ACC) phosphorylation. Pretreatment with compound C, an AMPK inhibitor, abolished the inhibitory effects of nobiletin on SREBP‐1c and FAS expressions. These results suggest that nobiletin may attenuate the high glucose‐induced lipid accumulation in HepG2 hepatocytes through modulation of AMPK signaling pathway, therefore preventing hepatic steatosis.