Deficiency of NLR family member NLRC5 alleviates alcohol induced hepatic injury and steatosis by enhancing autophagy of hepatocytes

Steatosis is regarded as an early response of the liver to excessive alcohol consumption, which ultimately results in alcoholic liver disease (ALD). Hepatocytes are the primary drivers of the pathological process known as he-patic damage and steatosis, which is characterized by significant fat accumulation and an abundance of fat vacuoles. NLRs, a family member of pattern recognition receptors, have recently been found to be crucial in liver disorders. In this study, we examined the possible impact of NLRC5, the largest NLR family member, on alcohol -induced fatty liver development using a gene knock-out mouse model. The mouse liver was severely damaged and developed steatosis as a result of chronic and excessive ethanol use, and this damage was prevented by the lack of NLRC5. Additionally, NLRC5 deletion reversed ethanol's ability to increase the serum concentrations of TG, T-CHO, ALT, and AST. Absence of NLRC5 reduced ethanol-stimulated aberrant expression of the vital reg-ulators of lipid synthesis and metabolism, SREBP-1c, FAS and PPAR-alpha. Furthermore, loss-and gain-of-function research indicated that NLRC5 might affect the autophagy pathway in alcohol-induced hepatic steatosis pro-gression. The functional role of NLRC5 in ALD is obviously impacted by the autophagy inducer rapamycin as well as the autophagy inhibitor 3-MA. Our research showed that NLRC5 was involved in ethanol-induced injury and steatosis of the liver, and may be considered a suitable therapeutic target for treating ALD.

Automated summary

Alcohol-induced fatty liver development is a common early response to excessive alcohol consumption. In this study, NLRC5, a member of the NLR family, was found to play a crucial role in the development of alcoholic liver disease. The absence of NLRC5 prevented liver damage and steatosis caused by chronic and excessive ethanol use. NLRC5 also regulated the expression of key factors involved in lipid synthesis and metabolism, and its functional role in alcoholic liver disease was influenced by the autophagy pathway.