Adipocyte-Derived PXR Signaling Is Dispensable for Diet-Induced Obesity and Metabolic Disorders in MiceS

Abstract

Pregnane X receptor (PXR) is a xenobiotic receptor that can be activated by numerous chemicals including endogenous hormones, dietary steroids, pharmaceutical agents, and environmental chemicals. PXR has been established to function as a xenobiotic sensor to coordinately regulate xenobiotic metabolism by regulating the expression of many enzymes and transporters required for xenobiotic metabolism. Recent studies have implicated a potentially important role for PXR in obesity and metabolic disease beyond xenobiotic metabolism, but how PXR action in different tissues or cell types contributes to obesity and metabolic disorders remains elusive. To investigate the role of adipocyte PXR in obesity, we generated a novel adipocyte-specific PXR deficient mouse model (PXRDAd). Notably, we found that loss of adipocyte PXR did not affect food intake, energy expenditure, and obesity in high-fat diet-fed male mice. PXRDAd mice also had similar obesity-associated metabolic disorders including insulin resistance and hepatic steatosis as control littermates. PXR deficiency in adipocytes did not affect expression of key adipose genes in PXRDAd mice. Our findings suggest that adipocyte PXR signaling may be dispensable in diet-induced obesity and metabolic disorders in mice. Further studies are needed to understand the role of PXR signaling in obesity and metabolic disorders in the future.