raw data of "Helicobacter hepaticus promotes hepatic steatosis through CdtB-induced mitochondrial stress and lipid metabolism reprogramming"

Host-pathogen interaction influences many non-infectious diseases, such as metabolic disease. Helicobacter hepaticus (H. hepaticus) infection was identified in some patients with metabolic dysfunction-associated steatotic liver disease (MASLD); however, the causal link and underlying mechanisms remain unknown. Here we report that H. hepaticus infection or overexpression of CdtB of H. hepaticus induces lipid deposition in hepatocytes, both in vivo and in vitro. Furthermore, we identify that CdtB translocates to mitochondria with the assistance of Hsp90, leading to a decrease in the activity of mitochondrial respiratory complex V due to its interaction with ATP5A1. Consequently, CdtB induces mitochondrial damage and disrupts lipid metabolism. Mechanistically, CdtB-induced lipogenesis requires the CdtB-mitochondrial ROS-mTORC1-SREBP1 axis and CdtB mediated the expression of NONO to strengthen the nuclear localization of Sterol regulatory element-binding protein 1 (SREBP1) that promote the de novo fatty acid synthesis in the hepatocytes. Moreover, the neutralization of CdtB significantly alleviates hepatic lipidosis in mice upon H. hepaticus infection. Furthermore, the nucleic acid of H. hepaticus has been detected in the liver tissues of some patients with MASLD, which suggests a certain correlation between liver infection with H. hepaticus and the occurrence and progression of MASLD. Our findings define the critical role of CdtB in the pathogenesis of H. hepaticus infection-induced hepatic lipidosis and suggest the therapeutic potential of CdtB.