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

作　　者：Yi-jie Li Rui-yu Wu Run-ping Liu Kai-yi Wu Ming-ning Ding Rong Sun Yi-qing Gu Fei Zhou Jian-zhi Wu Qi Zheng Shu-ni Duan Rong-rong Li Yin-hao Zhang Fang-hong Li Xiaojiaoyang Li 

机构地区：[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

出　　处：《Acta Pharmacologica Sinica》2023年第9期1826-1840,共15页中国药理学报（英文版）

基　　金：supported by grants from National Natural Science Foundation of China (Grant No.82274186 to XJYL,82274201 and 82004029 to RPL);the National High-Level Talents Special Support Program to XJYL;Beijing Nova Program of Science&Technology (Z201100006820025 and Z211100002121167 to RPL);Young Talents Promotion Project of China Association of Traditional Chinese Medicine (Grant No.2020-QNRC2-01 to XJYL and CACM-2020-QNRC2-04 to RPL);Beijing Municipal Science&Technology Commission (Grant No.7212174 to XJYL);Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (Grant No.ZYYCXTD-C-202006 to XJYL).

摘　　要：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 PPARαboth 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.

关 键 词：OBESITY brown adipose tissue UCP1 PPARa AURANTIO-OBTUSIN 

分 类 号：R589.2[医药卫生—内分泌]