Genetic ablation of diabetes-associated gene Ccdc92 reduces obesity and insulin resistance in mice

• Published in: iScience Vol. 26; no. 1; p. 105769
• Main Authors: Ren, Lu, Du, Wa, Song, Dan, Lu, Haocheng, Hamblin, Milton H., Wang, Chenran, Du, Chunying, Fan, Guo-Chang, Becker, Richard C., Fan, Yanbo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.01.2023; Elsevier
• Subjects: Cell biology; Cellular physiology; Pathophysiology; Pathophysiology; Cell biology; Cellular physiology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.105769

Multiple genome-wide association studies (GWAS) have identified specific genetic variants in the coiled-coil domain containing 92 (CCDC92) locus that is associated with obesity and type 2 diabetes in humans. However, the biological function of CCDC92 in obesity and insulin resistance remains to be explored. Utilizing wild-type (WT) and Ccdc92 whole-body knockout (KO) mice, we found that Ccdc92 KO reduced obesity and increased insulin sensitivity under high-fat diet (HFD) conditions. Ccdc92 KO inhibited macrophage infiltration and fibrosis in white adipose tissue (WAT), suggesting Ccdc92 ablation protects against adipose tissue dysfunction. Ccdc92 deletion also increased energy expenditure and further attenuated hepatic steatosis in mice on an HFD. Ccdc92 KO significantly inhibited the inflammatory response and suppressed the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome in WAT. Altogether, we demonstrated the critical role of CCDC92 in metabolism, constituting a potential target for treating obesity and insulin resistance. [Display omitted] •Ccdc92 deficiency reduces obesity and insulin resistance in mice after a HFD challenge•Ccdc92 KO inhibits inflammatory response in white adipose tissue from mice on HFD•Ccdc92 KO attenuates NF-κB signaling and reduces NLRP3 inflammasome activation Cell biology; Cellular physiology; Pathophysiology