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The function of xenobiotics receptors in metabolic diseases

Jinhang Zhang, Qingyi Jia, Yanping Li and Jinhan He
Drug Metabolism and Disposition November 22, 2022, DMD-AR-2022-000862; DOI: https://doi.org/10.1124/dmd.122.000862
Jinhang Zhang
1Department of Pharmacy, West China Hospital, China
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Qingyi Jia
2Department of Endocrinology and Metabolism, West China Hospital, China
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Yanping Li
1Department of Pharmacy, West China Hospital, China
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Jinhan He
1Department of Pharmacy, West China Hospital, China
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  • For correspondence: jinhanhe@scu.edu.cn
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Abstract

Metabolic diseases are a series of metabolic disorders that include obesity, diabetes, insulin resistance, hypertension, and hyperlipidemia. The increased prevalence of metabolic diseases has resulted in higher mortality and mobility rates over the past decades, and this has led to extensive research focusing on the underlying mechanisms. Xenobiotic receptors (XRs) are a series of xenobiotic-sensing nuclear receptors that regulate their downstream target genes expression, thus defending the body from xenobiotic and endotoxin attacks. XR activation is associated with the development of a number of metabolic diseases such as obesity, nonalcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D), and cardiovascular diseases, thus suggesting an important role for XRs in modulating metabolic diseases. However, the regulatory mechanism of XRs in the context of metabolic disorders under different nutrient conditions is complex and remains controversial. This review summarizes the effects of XRs on different metabolic components (cholesterol, lipids, glucose, and bile acids) in different tissues during metabolic diseases. As chronic inflammation plays a critical role in the initiation and progression of metabolic diseases, we also discuss the impact of XRs on inflammation to comprehensively recognize the role of XRs in metabolic diseases. This will provide new ideas for treating metabolic diseases by targeting XRs.

Significance Statement This review outlines the current understanding of xenobiotic receptors on nutrient metabolism and inflammation during metabolic diseases. This work also highlights the gaps in this field, which can be used to direct the future investigations on metabolic diseases treatment by targeting xenobiotic receptors.

  • inflammation
  • Receptor down-regulation
  • Copyright © 2020 American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 51 (2)
Drug Metabolism and Disposition
Vol. 51, Issue 2
1 Feb 2023
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Xenobiotic Receptors in metabolic diseases

Jinhang Zhang, Qingyi Jia, Yanping Li and Jinhan He
Drug Metabolism and Disposition November 22, 2022, DMD-AR-2022-000862; DOI: https://doi.org/10.1124/dmd.122.000862

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OtherArticle

Xenobiotic Receptors in metabolic diseases

Jinhang Zhang, Qingyi Jia, Yanping Li and Jinhan He
Drug Metabolism and Disposition November 22, 2022, DMD-AR-2022-000862; DOI: https://doi.org/10.1124/dmd.122.000862
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