Epithelial NAD⁺ depletion drives mitochondrial dysfunction and contributes to intestinal inflammation.

ABSTRACT:

Introduction

We have previously demonstrated that a pathologic downregulation of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1α) within the intestinal epithelium contributes to the pathogenesis of inflammatory bowel disease (IBD). However, the mechanism underlying downregulation of PGC1α expression and activity during IBD is not yet clear.

Methods

Mice (male; C57Bl/6, Villincre/+;Pgc1afl/fl mice, and Pgc1afl/fl) were subjected to experimental colitis and treated with nicotinamide riboside. Western blot, high-resolution respirometry, nicotinamide adenine dinucleotide (NAD+) quantification, and immunoprecipitation were used to in this study.

Results

We demonstrate a significant depletion in the NAD+ levels within the int

SUBMITTER: Novak EA 

PROVIDER: S-EPMC10512956 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature