High temperature ameliorates high-fat diet-induced obesity by promoting ceramide breakdown in skeletal muscle tissue  

作　　者：Qiankun Wang Lupeng Chen Junzhi Zhang Yue Liu Yi Jin Jian Wu Zhuqing Ren 

机构地区：[1]Key Laboratory of Agriculture Animal Genetics,Breeding and Reproduction of the Ministry of Education,College of Animal Science and Technology,Huazhong Agricultural University,Wuhan,Hubei 430070,China [2]College of Animal Science and Technology,Henan University of Science and Technology,Luoyang,Henan 471000,China [3]Frontiers Science Center for Animal Breeding and Sustainable Production,Wuhan,Hubei 430070,China [4]Hubei Hongshan Laboratory,Wuhan,Hubei 430070,China

出　　处：《Life Metabolism》2024年第5期1-16,共16页生命代谢（英文）

基　　金：supported by the National Natural Science Foundation of China(32172700);the Fundamental Research Funds for the Central Universities(2662023DKPY003 and 2662022DKPY002).

摘　　要：Obesity is considered an epidemic often accompanied by insulin resistance(IR).Heat treatment(HT)has been shown to prevent high-fat diet-induced IR in skeletal muscle,but the underlying mechanisms are poorly understood.In this study,we discovered that high temperature alleviated the hallmarks of obesity by promoting glycogen synthesis and lowering blood glucose levels in skeletal muscle tissue(SMT).Additionally,HT maintained the decay phase of heat shock factor 1(HSF1),leading to the activation of gene expression of heat shock proteins(HSPs),which contributed to the alleviation of IR in SMT of diet-induced obese(DIO)mice.Metabolomics and lipidomics analyses showed that HT promoted ceramide(Cer)breakdown,resulting in an elevation of both sphingomyelin(SM)and sphingosine,which further contributed to the amelioration of IR in SMT of DIO mice.Importantly,the increase in sphingosine was attributed to the heightened expression of the acid ceramidase N-acylsphingosine amidohydrolase 1(ASAH1),and the inhibition of ASAH1 attenuated HT-relieved IR in SMT of DIO mice.Surprisingly,high temperature increased the composition of Cer and cholesteryl ester in lipid droplets of skeletal muscle cells.This not only helped alleviate IR but also pre-vented lipotoxicity in SMT of DIO mice.These findings revealed a previously unknown connection between a high-temperature environment and sphingolipid metabolism in obesity,suggesting that high temperature can improve IR by promoting Cer catabo-lism in SMT of obese mice.

关 键 词：high temperature OBESITY insulin resistance ceramide breakdown lipid droplets 

分 类 号：R589.2[医药卫生—内分泌]