Serpina3c, a murine gene belonging to the serine protease inhibitor (Serpin) family with human homologue SerpinA3, plays crucial roles in physiological processes such as insulin secretion and adipogenesis. It is involved in multiple pathways, like regulating adipose tissue inflammation through the Cathepsin G/Integrin/AKT pathway [1]. Gene knockout mouse models have been valuable in understanding its functions.

In gene knockout mouse models, Serpina3c deficiency leads to various metabolic disorders. Serpina3c -/- mice show an impaired metabolic phenotype with more severe obesity, lower metabolic rates, glucose intolerance, and insulin insensitivity, associated with adipose tissue inflammation and apoptosis [1]. In non-alcoholic fatty liver disease (NAFLD), Apoe -/-/serpina3c -/- double knockout mice have exacerbated hepatic steatosis, inflammation, fibrosis, and necroptosis via the β-catenin/Foxo1/TLR4 signaling [2]. In obesity-related hypertriglyceridemia, Serpina3c global knockout and adipocyte-specific knockdown mice have more severe conditions due to activation of the Hif1α-glycolysis axis in adipose tissue [3].

In conclusion, Serpina3c is essential for maintaining normal metabolic functions. Gene knockout mouse models have revealed its role in metabolic diseases such as obesity, insulin resistance, NAFLD, and obesity-related hypertriglyceridemia. Understanding Serpina3c can provide potential therapeutic targets for these metabolic disorders.