Cyanidin-3-O-β-glucoside, a typical anthocyanin, exhibits antilipolytic effects in 3T3-L1 adipocytes during hyperglycemia: Involvement of FoxO1-mediated transcription of adipose triglyceride lipase

Elevated concentrations of circulating free fatty acids (FFAs) have been demonstrated to potentially link obesity, insulin resistance and type 2 diabetes. Inhibition of lipolysis reduces FFAs availability and improves insulin sensitivity. Anthocyanins from different plant foods were shown to improve hyperlipidemia and insulin resistance in vivo. In this study, cyanidin-3-O-β-glucoside (C3G), a typical anthocyanin was selected to examine its in vitro effects on high-glucose-induced lipolysis in cultured 3T3-L1 adipocytes. Incubation with C3G efficiently inhibited FFAs and glycerol release from the adipocytes during hyperglycemia in a dose- and time-dependent manner. C3G treatment also increased the activity of AMP-activated protein kinase, decreased the activity of glutamine:fructose 6-phosphate aminotransferase, reduced cellular UDP-N-acetylglucosamine production, thereby suppressing the hexosamine biosynthetic pathway. In addition, C3G attenuated high-glucose-promoted O-glycosylation of transcription factor FoxO1, resulting in decreased expression of adipose triglyceride lipase (ATGL). Our findings reveal a novel mechanism by which anthocyanin regulates FoxO1-mediated transcription of ATGL and thus inhibits adipocyte lipolysis, suggesting its potential therapeutic application in diabetes-associated hyperlipidemia.

Highlights► Anthocyanin C3G inhibits high-glucose-induced lipolysis in 3T3-L1 adipocytes. ► C3G stimulates AMP-activated protein kinase in high-glucose-incubated adipocytes. ► C3G attenuates high-glucose-induced overactivity of hexosamine pathway in adipocytes. ► FoxO1-mediated transcription of ATGL is involved in the antilipolytic effect of C3G.