ArticleBiochemical pharmacology2014
Role of human pregnane X receptor in high fat diet-induced obesity in pre-menopausal female mice.
Article in Biochemical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Cytochrome P450 3A gene family in gastric cancer: Unveiling diagnostic biomarkers and therapeutic targets for personalized treatment.World journal of clinical oncology · 2025Review
- Adipocyte-Derived PXR Signaling Is Dispensable for Diet-Induced Obesity and Metabolic Disorders in Mice.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Pregnane X Receptor and the Gut-Liver Axis: A Recent Update.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Pregnane X receptor exacerbates nonalcoholic fatty liver disease accompanied by obesity- and inflammation-prone gut microbiome signature.Biochemical pharmacology · 2021Article
- Review
- The Other Obesity Epidemic-Of Drugs and Bugs.Frontiers in endocrinology · 2020Review
- Cyp2b-null male mice are susceptible to diet-induced obesity and perturbations in lipid homeostasis.The Journal of nutritional biochemistry · 2019Article
- Gene Expression Profiling Reveals that PXR Activation Inhibits Hepatic PPARα Activity and Decreases FGF21 Secretion in Male C57Bl6/J Mice.International journal of molecular sciences · 2019Article
- The Sex-Gender Effects in the Road to Tailored Botanicals.Nutrients · 2019Review
- Nuclear receptors and liver disease: Summary of the 2017 basic research symposium.Hepatology communications · 2018Review
- High fat diet induced obesity is mitigated in Cyp3a-null female mice.Chemico-biological interactions · 2018Article
- Role of the pregnane X receptor in binge ethanol-induced steatosis and hepatotoxicity.The Journal of pharmacology and experimental therapeutics · 2018Article
- PXR: More Than Just a Master Xenobiotic Receptor.Molecular pharmacology · 2018Review
- Pregnane X receptor promotes ethanol-induced hepatosteatosis in mice.The Journal of biological chemistry · 2018Article
- Targeting nuclear receptors for the treatment of fatty liver disease.Pharmacology & therapeutics · 2017Review
- Novel functions of PXR in cardiometabolic disease.Biochimica et biophysica acta · 2016Review
- RNA-Seq reveals common and unique PXR- and CAR-target gene signatures in the mouse liver transcriptome.Biochimica et biophysica acta · 2016Article
- Nuclear receptors and nonalcoholic fatty liver disease.Biochimica et biophysica acta · 2016Review
- Acetylation of lysine 109 modulates pregnane X receptor DNA binding and transcriptional activity.Biochimica et biophysica acta · 2016Article
- Pregnane X Receptor and Cancer: Context-Specificity is Key.Nuclear receptor research · 2016Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Obesity is a complex metabolic disorder that is more prevalent among women. Until now, the only relevant rodent models of diet-induced obesity were via the use of ovariectomized ("postmenopausal") females. However, recent reports suggest that the xenobiotic nuclear receptor pregnane X receptor (PXR) may contribute to obesity. Therefore, we compared the roles of mouse and human PXRs in diet-induced obesity between wild type (WT) and PXR-humanized (hPXR) transgenic female mice fed either control or high-fat diets (HFD) for 16 weeks. HFD-fed hPXR mice gained weight more rapidly than controls, exhibited hyperinsulinemia, and impaired glucose tolerance. Fundamental differences were observed between control-fed hPXR and WT females: hPXR mice possessed reduced estrogen receptor α (ERα) but enhanced uncoupling protein 1 (UCP1) protein expression in white adipose tissue (WAT); increased protein expression of the hepatic cytochrome P450 3A11 (CYP3A11) and key gluconeogenic enzymes phosphoenolpyruvate carboxykinase and glucose 6-phosphatase, and increased total cholesterol. Interestingly, HFD ingestion induced both UCP1 and glucokinase protein expression in WT mice, but inhibited these enzymes in hPXR females. Unlike WT mice, CYP3A11 protein, serum 17β-estradiol levels, and WAT ERα expression were unaffected by HFD in hPXR females. Together, these studies indicate that the hPXR gene promotes obesity and metabolic syndrome by dysregulating lipid and glucose homeostasis while inhibiting UCP1 expression. Furthermore, our studies indicate that the human PXR suppresses the protective role of estrogen in metabolic disorders. Finally, these data identify PXR-humanized mice as a promising in vivo research model for studying obesity and diabetes in women.
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