Metabolic benefits of inhibition of p38 alpha in white adipose tissue in obesity
文献类型：期刊论文
| 作者 | Zhang, Shengjie1; Cao, Hongchao1; Li, Yan1; Jing, Yanyan1; Liu, Shengnan1; Ye, Cheng1; Wang, Hui1; Yu, Shuxian1; Zhang, Haibing1; Guo, Feifan1 |
| 刊名 | PLOS BIOLOGY
 |
| 出版日期 | 2018 |
| 卷号 | 16期号:5页码:e2004225 |
| ISSN号 | 1545-7885 |
| 关键词 | Metabolomics Calorie restriction Aging Vitamin E Amino acids Bile acids |
| 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. |
| 学科主题 | Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics |
| WOS关键词 | ACTIVATED PROTEIN-KINASE ; P38 MAP KINASE ; ADAPTIVE THERMOGENESIS ; INSULIN SENSITIVITY ; SKELETAL-MUSCLE ; ADULT HUMANS ; BROWN ; ADIPOCYTES ; FAT ; BEIGE |
| 语种 | 英语 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| WOS记录号 | WOS:000433987500010 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/696]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Key Lab Nutr Metab & Food Safety, Shanghai, Peoples R China; 2.Chinese Acad Sci, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China, 3.Fudan Univ, Zhongshan Hosp, Dept Endocrinol & Metab, Shanghai, Peoples R China; 4.Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China; 5.Fudan Univ, Shanghai Med Coll, Canc Ctr, Dept Head & Neck Surg, Shanghai, Peoples R China; 6.Minist Hlth, Key Lab Food Safety Risk Assessment, Beijing, Peoples R China; 7.Chinese Acad Sci, Shanghai Xuhui Cent Hosp, Shanghai Clin Ctr, Shanghai, Peoples R China; 8.Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Lab Mol Cell Biol, Shanghai, Peoples R China; 9.Chinese Acad Sci, Shanghai Inst Materia Med, 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):e2004225. |
| APA | Zhang, Shengjie.,Cao, Hongchao.,Li, Yan.,Jing, Yanyan.,Liu, Shengnan.,...&,.(2018).Metabolic benefits of inhibition of p38 alpha in white adipose tissue in obesity.PLOS BIOLOGY,16(5),e2004225. |
| MLA | Zhang, Shengjie,et al."Metabolic benefits of inhibition of p38 alpha in white adipose tissue in obesity".PLOS BIOLOGY 16.5(2018):e2004225. |
入库方式： OAI收割
来源：上海营养与健康研究所
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