Methionine and S-adenosylmethionine levels are critical regulators of PP2A activity modulating lipophagy during steatosis.

ABSTRACT:

Background & aims

Glycine N-methyltransferase (GNMT) expression is decreased in some patients with severe non-alcoholic fatty liver disease. Gnmt deficiency in mice (Gnmt-KO) results in abnormally elevated serum levels of methionine and its metabolite S-adenosylmethionine (SAMe), and this leads to rapid liver steatosis development. Autophagy plays a critical role in lipid catabolism (lipophagy), and defects in autophagy have been related to liver steatosis development. Since methionine and its metabolite SAMe are well known inactivators of autophagy, we aimed to examine whether high levels of both metabolites could block autophagy-mediated lipid catabolism.

Methods

We examined methionine levels in a cohort of 358 serum samples from steatotic patients. We used hepatocytes cul

SUBMITTER: Zubiete-Franco I 

PROVIDER: S-EPMC4718902 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature