Hepatocyte-specific perturbation of NAD⁺ biosynthetic pathways in mice induces reversible nonalcoholic steatohepatitis-like phenotypes.

ABSTRACT: Nicotinamide phosphoribosyltransferase (NAMPT) converts nicotinamide to NAD⁺. As low hepatic NAD⁺ levels have been linked to the development of nonalcoholic fatty liver disease, we hypothesized that ablation of hepatic Nampt would affect susceptibility to liver injury in response to diet-induced metabolic stress. Following 3 weeks on a low-methionine and choline-free 60% high-fat diet, hepatocyte-specific Nampt knockout (HNKO) mice accumulated less triglyceride than WT littermates but had increased histological scores for liver inflammation, necrosis, and fibrosis. Surprisingly, liver injury was also observed in HNKO mice on the purified control diet. This HNKO phenotype was associated with decreased abundance of mitochondrial proteins, especially proteins involved in

SUBMITTER: Dall M 

PROVIDER: S-EPMC8648833 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature