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

First Author  Ren L Year  2023
Journal  iScience Volume  26
Issue  1 Pages  105769
PubMed ID  36594018 Mgi Jnum  J:332421
Mgi Id  MGI:7424384 Doi  10.1016/j.isci.2022.105769
Citation  Ren L, et al. (2023) Genetic ablation of diabetes-associated gene Ccdc92 reduces obesity and insulin resistance in mice. iScience 26(1):105769
abstractText  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.
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