Metabolic benefits of inhibition of p38 alpha in white adipose tissue in obesity

doi:10.1371/journal.pbio.2004225

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 分子影像中心（筹）

	Metabolic benefits of inhibition of p38 alpha in white adipose tissue in obesity
	Zhang, Shengjie 9; Cao, Hongchao 9; Li, Yan 9; Jing, Yanyan 9; Liu, Shengnan 9; Ye, Cheng 9; Wang, Hui 9; Yu, Shuxian 9; Peng, Chengyuan 1; Hui, Lijian 6
刊名	PLOS BIOLOGY
	2018-05
卷号	16 期号:5
ISSN号	1545-7885
DOI	10.1371/journal.pbio.2004225
文献子类	Article
英文摘要	p38 has long been known as a central mediator of protein kinase A (PKA) signaling in brown adipocytes, which positively regulate the transcription of uncoupling protein 1 (UCP-1). However, the physiological role of p38 in adipose tissues, especially the white adipose tissue (WAT), is largely unknown. Here, we show that mice lacking p38 alpha in adipose tissues display a lean phenotype, improved metabolism, and resistance to dietinduced obesity. Surprisingly, ablation of p38 alpha causes minimal effects on brown adipose tissue (BAT) in adult mice, as evident from undetectable changes in UCP-1 expression, mitochondrial function, body temperature (BT), and energy expenditure. In contrast, genetic ablation of p38 alpha in adipose tissues not only markedly facilitates the browning in WAT upon cold stress but also prevents diet-induced obesity. Consistently, pharmaceutical inhibition of p38a remarkably enhances the browning of WAT and has metabolic benefits. Furthermore, our data suggest that p38a deficiency promotes white-to-beige adipocyte reprogramming in a cell-autonomous manner. Mechanistically, inhibition of p38 alpha stimulates the UCP-1 transcription through PKA and its downstream cAMP-response element binding protein (CREB), which form a positive feedback loop that functions to reinforce the white-to-beige phenotypic switch during cold exposure. Together, our study reveals that inhibition of p38 alpha is able to promote WAT browning and confer metabolic benefits. Our study also indicates that p38 alpha in WAT represents an exciting pharmacological target to combat obesity and metabolic diseases.
资助项目	Ministry of Science and Technology of China[2016YFA0500102] ; Ministry of Science and Technology of China[2016YFC1304905] ; National Natural Science Foundation of China[31525012] ; National Natural Science Foundation of China[31600954] ; National Natural Science Foundation of China[31371189] ; National Natural Science Foundation of China[81570768] ; National Natural Science Foundation of China[81471016] ; One Hundred Talent Program of Chinese Academy of Sciences[00000000] ; Chinese Academy of Sciences[ZDBS-SSW-DQC-02] ; Chinese Academy of Sciences[ZDRW-ZS-2017-1] ; Chinese Academy of Sciences[XDA12040324] ; Chinese Academy of Sciences[XDA12020108] ; Chinese Academy of Sciences/State Administration of Foreign Experts Affairs International Partnership Program for Creative Research Teams[00000000]
WOS关键词	ACTIVATED PROTEIN-KINASE ; P38 MAP KINASE ; ADAPTIVE THERMOGENESIS ; INSULIN SENSITIVITY ; SKELETAL-MUSCLE ; ADULT HUMANS ; BROWN ; ADIPOCYTES ; FAT ; BEIGE
WOS研究方向	Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000433987500010
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279772]
专题	分子影像中心（筹）
通讯作者	Ying, Hao
作者单位	1.Chinese Acad Sci, Shanghai Inst Materia Med, Shanghai, Peoples R China; 2.Fudan Univ, Zhongshan Hosp, Dept Endocrinol & Metab, Shanghai, Peoples R China; 3.Chinese Acad Sci, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China 4.Chinese Acad Sci, Shanghai Xuhui Cent Hosp, Shanghai Clin Ctr, Shanghai, Peoples R China; 5.Fudan Univ, Shanghai Med Coll, Canc Ctr, Dept Head & Neck Surg, Shanghai, Peoples R China; 6.Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Lab Mol Cell Biol, Shanghai, Peoples R China; 7.Minist Hlth, Key Lab Food Safety Risk Assessment, Beijing, Peoples R China; 8.Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China; 9.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Key Lab Nutr Metab & Food Safety, Shanghai, Peoples R China;
推荐引用方式 GB/T 7714	Zhang, Shengjie,Cao, Hongchao,Li, Yan,et al. Metabolic benefits of inhibition of p38 alpha in white adipose tissue in obesity[J]. PLOS BIOLOGY,2018,16(5).
APA	Zhang, Shengjie.,Cao, Hongchao.,Li, Yan.,Jing, Yanyan.,Liu, Shengnan.,...&Ying, Hao.(2018).Metabolic benefits of inhibition of p38 alpha in white adipose tissue in obesity.PLOS BIOLOGY,16(5).
MLA	Zhang, Shengjie,et al."Metabolic benefits of inhibition of p38 alpha in white adipose tissue in obesity".PLOS BIOLOGY 16.5(2018).