2. Academic Validation
  3. Hyperoside prevents high-fat diet-induced obesity by increasing white fat browning and lipophagy via CDK6-TFEB pathway

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

  • J Ethnopharmacol. 2023 Feb 11;116259. doi: 10.1016/j.jep.2023.116259.
Siyao Cheng 1,  Xintao Ni 1,  Yanjing Yao 2,  Yunxia Sun 3,  Xiaofeng Yu 3,  Daozong Xia 2,  Zhenggang Yang 4,  Miaofen G Hu 5,  Xiaoli Hou 6
Affiliations

Affiliations

  • 1 School of Life Sciences, Zhejiang Chinese Medical University, China.
  • 2 School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, China.
  • 3 Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, China.
  • 4 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
  • 5 Department of Medicine, Division of Hematology and Oncology, Tufts Medical Center, Boston, MA, USA.
  • 6 Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, China. Electronic address: [email protected].
PMID: 36781055 DOI: 10.1016/j.jep.2023.116259
Abstract

Ethnopharmacological relevance: 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.

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

Materials and methods: 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.

Results: 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.

Keywords

Beige cell; CDK6; Differentiation; Hyperoside; Obesity; Thermogenesis.

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