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Aurantio-obtusin ameliorates obesity by activating PPARα-dependent mitochondrial thermogenesis in brown adipose tissues

Authors :
Li, Yi-jie
Wu, Rui-yu
Liu, Run-ping
Wu, Kai-yi
Ding, Ming-ning
Sun, Rong
Gu, Yi-qing
Zhou, Fei
Wu, Jian-zhi
Zheng, Qi
Duan, Shu-ni
Li, Rong-rong
Zhang, Yin-hao
Li, Fang-hong
Li, Xiaojiaoyang
Source :
Acta Pharmacologica Sinica; September 2023, Vol. 44 Issue: 9 p1826-1840, 15p
Publication Year :
2023

Abstract

Obesity contributes to the progression of various chronic diseases, and shortens life expectancy. With abundant mitochondria, brown adipose tissue (BAT) dissipates energy through heat to limit weight gain and metabolic dysfunction in obesity. Our previous studies have shown that aurantio-obtusin (AO), a bioactive ingredient in Chinese traditional medicine Cassiae semensignificantly improves hepatic lipid metabolism in a steatotic mouse model. In the current study we investigated the effects of AO on lipid metabolism in the BAT of diet-induced obesity mice and in oleic acid and palmitic acid (OAPA)-stimulated primary mature BAT adipocytes. Obese mice were established by feeding a HFHS diet for 4 weeks, and then administered AO (10 mg/kg, i.g.) for another 4 weeks. We showed that AO administration significantly increased the weight of BAT and accelerated energy expenditure to protect the weight increase in the obese mice. Using RNA sequencing and molecular biology analysis we found that AO significantly enhanced mitochondrial metabolism and UCP1 expression by activating PPARα both in vivo and in vitro in the primary BAT adipocytes. Interestingly, AO administration did not improve metabolic dysfunction in the liver and white adipose tissue of obese mice after interscapular BAT excision. We demonstrated that low temperature, a trigger of BAT thermogenesis, was not a decisive factor for AO to stimulate the growth and activation of BATs. This study uncovers a regulatory network of AO in activating BAT-dependent lipid consumption and brings up a new avenue for the pharmaceutical intervention in obesity and related comorbidities.

Details

Language :
English
ISSN :
16714083 and 17457254
Volume :
44
Issue :
9
Database :
Supplemental Index
Journal :
Acta Pharmacologica Sinica
Publication Type :
Periodical
Accession number :
ejs62906255
Full Text :
https://doi.org/10.1038/s41401-023-01089-4