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

International Journal of Biological Sciences 2026 Open access

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Authors: Guangfa Yin, Yongqing Liu, Xianhe Teng, Shuqi Sun, Beibei Chen, Xinyu Wang, Tao Yang, Ying Wang, Hanyang Xu, Yu-sheng Chen, Guowei Gan, Yuxian Shen
+1 more Juntang Shao
DOI: 10.7150/ijbs.125688
Cited by: 2

Abstract

, demonstrated that SAMHD1 promoted lipid droplet accumulation. Conversely, hepatocyte-specific SAMHD1 knockout reduced steatosis and liver injury in diet-induced MASLD mouse models. Mechanistically, SAMHD1 enhanced the proteolytic activation of SREBP1 and SREBP2 by upregulating SCAP, S1P, and S2P in a cohesin complex-dependent manner. Collectively, these findings identify hepatocyte SAMHD1 as a promoter of liver steatosis through SREBP activation and highlight it as a potential therapeutic target for MASLD.

Fields of Study & Subjects

Liver Disease Diagnosis and Treatment Liver Diseases and Immunity Cholesterol and Lipid Metabolism

Publication details

Journal / source
International Journal of Biological Sciences
Publisher
Ivyspring International Publisher
Volume
22
Issue
2
Pages
876–894
Publication date
1 January 2026
Language
EN