SHMT2 Reduces Fatty Liver But is Necessary for Liver Inflammation and Fibrosis in Mice.

Document Type

Article

Publication Date

2-12-2024

Publication Title

Commun Biol

Abstract

Non-alcoholic fatty liver disease is associated with an irregular serine metabolism. Serine hydroxymethyltransferase 2 (SHMT2) is a liver enzyme that breaks down serine into glycine and one-carbon (1C) units critical for liver methylation reactions and overall health. However, the contribution of SHMT2 to hepatic 1C homeostasis and biological functions has yet to be defined in genetically modified animal models. We created a mouse strain with targeted SHMT2 knockout in hepatocytes to investigate this. The absence of SHMT2 increased serine and glycine levels in circulation, decreased liver methylation potential, and increased susceptibility to fatty liver disease. Interestingly, SHMT2-deficient mice developed simultaneous fatty liver, but when fed a diet high in fat, fructose, and cholesterol, they had significantly less inflammation and fibrosis. This study highlights the critical role of SHMT2 in maintaining hepatic 1C homeostasis and its stage-specific functions in the pathogenesis of NAFLD.

Medical Subject Headings

Animals; Mice; Fibrosis; Glycine; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Serine

PubMed ID

38347107

Volume

7

Issue

1

First Page

173

Last Page

173

Find It @ Sladen

Share

COinS