Article

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

Yi-jie Li1, Rui-yu Wu2, Run-ping Liu2, Kai-yi Wu3, Ming-ning Ding1, Rong Sun3, Yi-qing Gu2, Fei Zhou1, Jian-zhi Wu1, Qi Zheng2, Shu-ni Duan2, Rong-rong Li3, Yin-hao Zhang1, Fang-hong Li2, Xiaojiaoyang Li1
1 School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China
2 School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China
3 The Second Hospital of Shandong University, Shandong University, Ji-nan 250033, China
Correspondence to: Run-ping Liu: liurunping@bucm.edu.cn, Xiaojiaoyang Li: xiaojiaoyang.li@bucm.edu.cn,
DOI: 10.1038/s41401-023-01089-4
Received: 22 January 2023
Accepted: 4 April 2023
Advance online: 24 April 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 semen significantly 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.
Keywords: obesity; brown adipose tissue; UCP1; PPARα; aurantio-obtusin

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