ASC Regulates Subcutaneous Adipose Tissue Lipogenesis and Lipolysis via p53/AMPK alpha Axis

作者全名："Chen, Hong; Pei, Qilin; Tao, Linfen; Xia, Jing; Lu, Guocai; Zong, Ying; Xie, Wenhua; Li, Wanqing; Huang, Chenglong; Zeng, Ting; Yu, Xinyu; Wang, Weixuan; Chen, Gaojun; Yang, Song; Cheng, Rui; Li, Xi"

作者地址："[Chen, Hong; Pei, Qilin; Xia, Jing; Xie, Wenhua; Li, Wanqing; Huang, Chenglong; Zeng, Ting; Yu, Xinyu; Wang, Weixuan; Chen, Gaojun; Yang, Song; Cheng, Rui; Li, Xi] Chongqing Med Univ, Sch Basic Med, Inst Life Sci, Chongqing 400016, Peoples R China; [Tao, Linfen] Fujian Med Univ, Sch Med Technol & Engn, Dept Lab Med, Fuzhou 350001, Peoples R China; [Lu, Guocai; Zong, Ying] Second Mil Med Univ, Fac Naval Med, Dept Hlth Toxicol, Shanghai 200433, Peoples R China"

通信作者："Cheng, R; Li, X (通讯作者)，Chongqing Med Univ, Sch Basic Med, Inst Life Sci, Chongqing 400016, Peoples R China."

来源：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

ESI学科分类：CHEMISTRY

WOS号：WOS:000851157200001

JCR分区：Q2

影响因子：5.6

年份：2022

卷号：23

期号：17

开始页：　

结束页：　

文献类型：Article

关键词：ASC; lipogenesis; lipolysis; p53; AMPK alpha

摘要："Obesity has become an extensive threat to human health due to associated chronic inflammation and metabolic diseases. Apoptosis-associated speck-like protein (ASC) is a critical link between inflammasome and apoptosis-inducing proteins. In this study, we aimed to clarify the role of ASC in lipid metabolism. With high-fat diet (HFD) and knockout leptin gene mice (ob/ob), we found that ASC expression in subcutaneous adipose tissue (SAT) correlated with obesity. It could also positively regulate the reprogramming of cellular energy metabolism. Stromal vascular fractions (SVF) cells derived from the SAT of Asc(-/-) mice or SVF from wild-type (WT) mice transfected with ASC siRNA were used to further investigate the underlying molecular mechanisms. We found ASC deficiency could lead to lipogenesis and inhibit lipolysis in SAT, aggravating lipid accumulation and impairing metabolic balance. In addition, our results showed that p53 and AMPK alpha expression were inhibited in SAT when ASC level was low. p53 and AMP-activated protein kinase alpha (AMPK alpha) were then assessed to elucidate whether they were downstream of ASC in regulating lipid metabolism. Our results revealed that ASC deficiency could promote lipid accumulation by increasing lipogenesis and decreasing lipolysis through p53/AMPK alpha axis. Regulation of ASC on lipid metabolism might be a novel therapeutic target for obesity."

基金机构："National Key R&D Program of China [2018YFA0800401]; National Natural Science Foundation of China [81770861, 82070899, 82011530460]; fundamental research and frontier exploration project of Yuzhong district, Chongqing [20210123, 20180151]; general project of natural sciences foundation of Chongqing [cstc2020jcyj-msxmX0306]"

基金资助正文："This research was supported by the National Key R&D Program of China (2018YFA0800401) to Xi Li; the National Natural Science Foundation of China (No. 81770861, 82070899, and 82011530460) to Xi Li; the fundamental research and frontier exploration project of Yuzhong district, Chongqing, grant number 20210123 to Rui Cheng and 20180151 to Song Yang; the general project of natural sciences foundation of Chongqing, grant number cstc2020jcyj-msxmX0306 to Song Yang."