Pregnane X receptor activation remodels glucose metabolism to promote NAFLD development in obese mice.

ABSTRACT:

Objective

Both obesity and exposure to chemicals may induce non-alcoholic fatty liver disease (NAFLD). Pregnane X Receptor (PXR) is a central target of metabolism disrupting chemicals and disturbs hepatic glucose and lipid metabolism. We hypothesized that the metabolic consequences of PXR activation may be modified by existing obesity and associated metabolic dysfunction.

Methods

Wildtype and PXR knockout male mice were fed high-fat diet to induce obesity and metabolic dysfunction. PXR was activated with pregnenolone-16α-carbonitrile. Glucose metabolism, hepatosteatosis, insulin signaling, glucose uptake, liver glycogen, plasma and liver metabolomics, and liver, white adipose tissue, and muscle transcriptomics were investigated.

Results

PXR activation aggravated obesi

SUBMITTER: Karpale M 

PROVIDER: S-EPMC10415798 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature