Hepatocyte SAMHD1 Deficiency Attenuates Hepatic Steatosis via Suppression of SREBP Activation in a Mouse Model of Metabolic-Associated Steatotic Liver Disease.

ABSTRACT: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disorders and a growing public health concern. Sterile alpha motif and HD domain-containing protein 1 (SAMHD1), a dNTP triphosphohydrolase, is known for its roles in nucleotide metabolism, antiviral defense, and immune regulation, but its function in hepatocytes and contribution to MASLD pathogenesis remain unclear. In this study, we observed that hepatic SAMHD1 expression was markedly increased in MASLD patient samples and diet-induced MASLD mouse models. In vitro, mimicking MASLD-associated dyslipidemia with palmitic acid, oleic acid, and cholesterol upregulated SAMHD1 expression, an IFN-γ-induced protein, accompanied by increased IFN-γ receptor 1 expression and STAT1 activation in

SUBMITTER: Yin G 

PROVIDER: S-EPMC12781173 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature