ER stress-induced upregulation of NNMT contributes to alcohol-related fatty liver development.

ABSTRACT:

Background & aims

N-nicotinamide methyltransferase (NNMT) is emerging as an important enzyme in the regulation of metabolism. NNMT is highly expressed in the liver. However, the exact regulatory mechanism(s) underlying NNMT expression remains unclear and its potential involvement in alcohol-related liver disease (ALD) is completely unknown.

Methods

Both traditional Lieber-De Carli and the NIAAA mouse models of ALD were employed. A small-scale chemical screening assay and a chromatin immunoprecipitation assay were performed. NNMT inhibition was achieved via both genetic (adenoviral short hairpin RNA delivery) and pharmacological approaches.

Results

Chronic alcohol consumption induces endoplasmic reticulum (ER) stress and upregulates NNMT expression in the liver. ER str

SUBMITTER: Song Q 

PROVIDER: S-EPMC8301603 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature