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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 (PXRΔAd). Notably, we found that loss of adipocyte PXR did not affect food intake, energy expenditure, and obesity in high-fat diet-fed male mice. PXRΔAd 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 PXRΔAd 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.
SIGNIFICANCE STATEMENT The authors demonstrate that deficiency of adipocyte pregnane X receptor (PXR) does not affect diet-induced obesity or metabolic disorders in mice and infers that adipocyte PXR signaling may not play a key role in diet-induced obesity. More studies are needed to understand the tissue-specific role of PXR in obesity.
Footnotes
- Received February 24, 2023.
- Accepted May 15, 2023.
This work was supported in part by National Institutes of Health National Institute of Environmental Health Sciences (NIEHS) [Grant R01ES023470], National Heart, Lung, and Blood Institute [Grants R01HL167206, R01HL123358, and R01HL131925], and National Institute of General Medical Sciences [Grant P30GM127211]; the American Heart Association [Grant 19TPA34890065]; a National Institutes of Health NIEHS T32 training grant [Grant T32ES018827] (to R.H.); and an American Heart Association predoctoral fellowship [Grant 23PRE1018751] (to R.H.).
F.W. and J.L. contributed equally to this work.
No author has an actual or perceived conflict of interest with the contents of this article.
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- Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics
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