Covalent inhibition of endoplasmic reticulum chaperone GRP78 disconnects the transduction of ER stress signals to inflammation and lipid accumulation in diet-induced obese mice.

ABSTRACT: Targeting endoplasmic reticulum (ER) stress, inflammation, and metabolic dysfunctions may halt the pathogenesis of obesity and thereby reduce the prevalence of diabetes, cardiovascular disesases, and cancers. The present study was designed to elucidate the mechnaisms by which plant-derived celastrol ameliorated inflammation and lipid accumulation in obesity. The mouse model of diet-induced obesity was induced by feeding high-fat diet for 3 months and subsequently intervented with celastrol for 21 days. Hepatic and adipose tissues were analyzed for lipid accumulation, macrophage activation, and biomarker expression. As result, celastrol effectively reduced body weight, suppressed ER stress, inflammation, and lipogenesis while promoted hepatic lipolysis. RNA-sequencing revealed that celastro

SUBMITTER: Luo D 

PROVIDER: S-EPMC8828050 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature