Cav3.2 deletion attenuates nonalcoholic fatty liver disease in mice

•Cav3.2 knockout (Cav3.2 KO) improves hepatic steatosis, liver injury and metabolic syndrome in NAFLD mice model.•Further studies showed that Cav3.2 KO inhibited HFD-induced hepatic oxidative stress, inflammation and hepatocyte apoptosis.•We found that Cav3.2 KO also attenuated the hepatic lipid accumulation, oxidative stress, inflammation and hepatocyte apoptosis in palmitic acid/oleic acid (PAOA)-treated primary hepatocytes.•Cav3.2 KO-mediated effects were dependent on its interaction with CaMKII signaling. Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and represents the main cause of liver cirrhosis and hepatocellular carcinoma. Cav3.2 is a T-type calcium channel that is widely present in tissues throughout the body and plays a vital role in energy and metabolic balance. However, the effects of Cav3.2 on the NFALD remain unclear. Here, we investigated the role 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) improved hepatic steatosis, liver injury and metabolic syndrome in an NAFLD mouse model. We provided evidence that Cav3.2 KO inhibited HFD-induced hepatic oxidative stress, inflammation and hepatocyte apoptosis. In addition, Cav3.2 KO also attenuated hepatic lipid accumulation, oxidative stress, inflammation and hepatocyte apoptosis in palmitic acid/oleic acid (PAOA)-treated primary hepatocytes. These results suggest that therapeutic approaches targeting Cav3.2 provide effective approaches for treating NAFLD.