Cav3.2 deletion attenuates nonalcoholic fatty liver disease in mice

Abstract

Abstract Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and also the main cause of liver cirrhosis and hepatocellular carcinoma. Cav3.2 channel is an important member of T-type calcium channel and plays a vital role in energy and metabolic balance. However, the effects of Cav3.2 on NFALD remain unclear. Here, we aimed to investigate the function of Cav3.2 channel in the development and progression of NAFLD. After 16 weeks on a high-fat diets (HFD), Cav3.2 knockout (Cav3.2 KO) improves hepatic steatosis, liver injury and metabolic syndrome in NAFLD mice model. We provided evidence that Cav3.2 KO inhibited HFD-induced hepatic oxidative damage, inflammation and hepatocyte apoptosis. In addition, Cav3.2 KO also attenuated the hepatic lipid accumulation, oxidative damage, inflammation and hepatocyte apoptosis in palmitic acid/oleic acid (PAOA)-treated primary hepatocytes. Further, Cav3.2 KO-mediated liver protection function were dependent on its interaction with CaMKII signaling. These results suggest that therapeutic approaches targeting Cav3.2 provide effective approaches for treating NAFLD.