Acteoside improves adipocyte browning by CDK6-mediated mTORC1-TFEB pathway

Yunxia Sun; Xintao Ni; Siyao Cheng; Xiaofeng Yu; Xiaoqin Jin; Liangxin Chen; Zhenggang Yang; Daozong Xia; Zhe Chen; Miaofen G Hu; Xiaoli Hou

doi:10.1016/j.bbalip.2023.159364

Acteoside improves adipocyte browning by CDK6-mediated mTORC1-TFEB pathway

Biochim Biophys Acta Mol Cell Biol Lipids. 2023 Sep;1868(9):159364. doi: 10.1016/j.bbalip.2023.159364. Epub 2023 Jul 9.

Authors

Yunxia Sun¹, Xintao Ni², Siyao Cheng², Xiaofeng Yu², Xiaoqin Jin², Liangxin Chen³, Zhenggang Yang⁴, Daozong Xia³, Zhe Chen⁵, Miaofen G Hu⁶, Xiaoli Hou⁷

Affiliations

¹ School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China; Academy of Chinese Medical Science, Zhejiang Chinese Medical University, China.
² Academy of Chinese Medical Science, Zhejiang Chinese Medical University, China.
³ School of Pharmaceutical Sciences, 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 The Second Clinical Medical College, Zhejiang Chinese Medical University, China.
⁶ Department of Medicine, Division of Hematology and Oncology, Tufts Medical Center, Boston, MA, USA.
⁷ School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China; Academy of Chinese Medical Science, Zhejiang Chinese Medical University, China. Electronic address: 20081005@zcmu.edu.cn.

PMID: 37433343
DOI: 10.1016/j.bbalip.2023.159364

Abstract

Adipocyte browning increases energy expenditure by thermogenesis, which has been considered a potential strategy against obesity and its related metabolic diseases. Phytochemicals derived from natural products with the ability to improve adipocyte thermogenesis have aroused extensive attention. Acteoside (Act), a phenylethanoid glycoside, exists in various medicinal or edible plants and has been shown to regulate metabolic disorders. Here, the browning effect of Act was evaluated by stimulating beige cell differentiation from the stromal vascular fraction (SVF) in the inguinal white adipose tissue (iWAT) and 3T3-L1 preadipocytes, and by converting the iWAT-SVF derived mature white adipocytes. Act improves adipocyte browning by differentiation of the stem/progenitors into beige cells and by direct conversion of mature white adipocytes into beige cells. Mechanistically, Act inhibited CDK6 and mTOR, and consequently relieved phosphorylation of the transcription factor EB (TFEB) and increased its nuclear retention, leading to induction of PGC-1α, a driver of mitochondrial biogenesis, and UCP1-dependent browning. These data thus unveil a CDK6-mTORC1-TFEB pathway that regulates Act-induced adipocyte browning.

Keywords: Acteoside; Beige cell; CDK6; Differentiation; TFEB; mTORC1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipocytes, White / metabolism
Adipose Tissue, White* / metabolism
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
Cyclin-Dependent Kinase 6 / metabolism
Cyclin-Dependent Kinase 6 / pharmacology
Humans
Mechanistic Target of Rapamycin Complex 1 / metabolism
Metabolic Diseases* / metabolism
Obesity / drug therapy
Obesity / metabolism

Substances

Mechanistic Target of Rapamycin Complex 1
acteoside
TFEB protein, human
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
CDK6 protein, human
Cyclin-Dependent Kinase 6