TFEB
山楂
金丝桃苷
药理学
自噬
贯叶连翘
生物
化学
医学
生物化学
槲皮素
植物
抗氧化剂
细胞凋亡
作者
Siyao Cheng,Xintao Ni,Yanjing Yao,Yunxia Sun,Xiaofeng Yu,Daozong Xia,Zhenggang Yang,Miaofen G. Hu,Xiaoli Hou
标识
DOI:10.1016/j.jep.2023.116259
摘要
Hypericum perforatum L. (genus Hypericum, family Hypericaceae) is a flowering plant native to Europe, North Africa and Asia, which can be used in the treatment of psychiatric disorder, cardiothoracic depression and diabetes. Crataegus pinnatifida Bunge (genus Crataegus pinnatifida Bunge, family Rosaceae) was another traditional Chinese medicine for treating hyperlipidemia. Hyperoside (Hype), a major flavonoid glycoside component of Hypericum perforatum L. and Crataegus pinnatifida Bunge, possesses multiple physiological activities, such as anti-inflammatory and antioxidant effects. However, the role of Hype on obesity and related metabolic diseases still needs to be further investigated.We explored the effect of Hype on high-fat diet (HFD)-induced obesity and its metabolic regulation on white fat tissues.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.Hype protects mice from HFD-induced obesity by increasing energy expenditure of white fat tissue via CDK6-TFEB pathway.
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