Hyperoside prevents high-fat diet-induced obesity by increasing white fat browning and lipophagy via CDK6-TFEB pathway

We explored the effect of Hype on high-fat diet (HFD)-induced obesity and its metabolic regulation on white fat tissues. Materials and

Hype protects mice from HFD-induced obesity by increasing energy expenditure of white fat tissue via CDK6-TFEB pathway.

In vivo four-week-old male C57BL/6J mice were randomly assigned to vehicle (0.5% methycellulose) and Hype (80 mg/kg/day by gavage) group under a normal chow diet (NCD) or HFD for 8 weeks. In vitro, 3T3-L1 preadipocyte cell line and primary stromal vascular fraction (SVF) cells from inguinal white adipose tissue (iWAT) of mice were used to investigate the molecular mechanisms of Hype regulation on adipocyte energy metabolism.

Hype treatment in vivo promotes UCP1-dependent white to beige fat transition, increases glucose and lipid metabolism, and resists HFD-induced obesity. Meanwhile, Hype induces lipophagy, a specific autophagy that facilitates the breakdown of lipid droplets, and blocking autophagy partially reduces UCP1 expression. Mechanistically, Hype inhibited CDK6, leading to the increased nuclear translocation of TFEB, while overexpression of CDK6 partially reversed the enhancement of UCP1 by Hype. Conclusions: Hype protects mice from HFD-induced obesity by increasing energy expenditure of white fat tissue via CDK6-TFEB pathway.