Caspase-1 Deficiency Modulates Adipogenesis through Atg7-Mediated Autophagy: An Inflammatory-Independent Mechanism

作者全名：Wang, Yumeng; Chen, Gaojun; Xu, Min; Cui, Yewei; He, Weijiong; Zeng, Hongxiang; Zeng, Ting; Cheng, Rui; Li, Xi

作者地址：[Wang, Yumeng; Chen, Gaojun; Xu, Min; Cui, Yewei; He, Weijiong; Zeng, Hongxiang; Zeng, Ting; Cheng, Rui; Li, Xi] Chongqing Med Univ, Inst Life Sci, Sch Basic Med, Chongqing 400016, Peoples R China

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

来源：BIOMOLECULES

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001210314300001

JCR分区：Q1

影响因子：4.8

年份：2024

卷号：14

期号：4

开始页：　

结束页：　

文献类型：Article

关键词：Caspase-1; adipogenesis; autophagy; Atg7

摘要：Obesity stands as a significant risk factor for type 2 diabetes, hyperlipidemia, and cardiovascular diseases, intertwining increased inflammation and decreased adipogenesis with metabolic disorders. Studies have highlighted the correlation between Caspase-1 and inflammation in obesity, elucidating its essential role in the biological functions of adipose tissue. However, the impact of Caspase-1 on adipogenesis and the underlying mechanisms remain largely elusive. In our study, we observed a positive correlation between Caspase-1 expression and obesity and its association with adipogenesis. In vivo experiments revealed that, under normal diet conditions, Caspase-1 deficiency improved glucose homeostasis, stimulated subcutaneous adipose tissue expansion, and enhanced adipogenesis. Furthermore, our findings indicate that Caspase-1 deficiency promotes the expression of autophagy-related proteins and inhibits autophagy with 3-MA or CQ blocked Caspase-1 deficiency-induced adipogenesis in vitro. Notably, Caspase-1 deficiency promotes adipogenesis via Atg7-mediated autophagy activation. In addition, Caspase-1 deficiency resisted against high-fat diet-induced obesity and glucose intolerance. Our study proposes the downregulation of Caspase-1 as a promising strategy for mitigating obesity and its associated metabolic disorders.

基金机构：National Key R&D Program of China

基金资助正文：No Statement Available