ArticleBiochemical pharmacology2021
Pregnane X receptor exacerbates nonalcoholic fatty liver disease accompanied by obesity- and inflammation-prone gut microbiome signature.
Article in Biochemical pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Perinatal phlorizin alleviates maternal high-fat diet-induced metabolic syndrome in female mouse offspring and is associated with modulation of the gut microbiota.Frontiers in nutrition · 2026Article
- Role of the xenobiotic-activated pregnane X receptor in type 1 and type 2 diabetes in male mice.Biochemical pharmacology · 2026Article
- Pregnane X receptor (NR1I2) deficiency in mice reveals context-dependent regulation of inflammatory homeostasis.Frontiers in immunology · 2026Review
- Transition From a High-Sugar and Butter to a Standard Diet Leads to Cecal Dysbiosis, Disrupts Intestinal Homeostasis, and Favors Increased Ethanol Consumption and Preference.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Physiological Functions and Pathological Roles of PXR.Journal of the Endocrine Society · 2025Review
- Mechanisms and Therapeutic Advances of PXR in Metabolic Diseases and Cancer.International journal of molecular sciences · 2025Review
- Mendelian randomization analysis reveals causal links between gut microbiota, serum metabolites, and aneurysm risk.Medicine · 2025Article
- Orchestration of Gut-Liver-Associated Transcription Factors in MAFLD: From Cross-Organ Interactions to Therapeutic Innovation.Biomedicines · 2025Review
- Ruminococcus gnavus in the gut: driver, contributor, or innocent bystander in steatotic liver disease?The FEBS journal · 2025Review
- Unlocking the potential: FKK6 as a microbial mimicry-based therapy for chronic inflammation-associated colorectal cancer in a murine model.The Journal of pharmacology and experimental therapeutics · 2025Article
- Bile acid signaling mediates gut microbiota regulation of host lipid metabolism.Frontiers in microbiology · 2025Review
- Review
- Nidogen 2 Overexpression Promotes Hepatosteatosis and Atherosclerosis.International journal of molecular sciences · 2024Article
- Molecular targets of PXR-dependent ethanol-induced hepatotoxicity in female mice.Biochemical pharmacology · 2024Article
- Water-soluble garlic polysaccharide (WSGP) improves ulcerative volitis by modulating the intestinal barrier and intestinal flora metabolites.Scientific reports · 2024Article
- B3galt5 functions as a PXR target gene and regulates obesity and insulin resistance by maintaining intestinal integrity.Nature communications · 2024Article
- Article
- Pregnane X receptor knockout mitigates weight gain and hepatic metabolic dysregulation in female C57BL/6 J mice on a long-term high-fat diet.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- The roles of nuclear receptors in cholesterol metabolism and reverse cholesterol transport in nonalcoholic fatty liver disease.Hepatology communications · 2024Review
- Gut liver brain axis in diseases: the implications for therapeutic interventions.Signal transduction and targeted therapy · 2023Review
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Authors and funding
9 authors.
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Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease due to the current epidemics of obesity and diabetes. The pregnane X receptor (PXR) is a xenobiotic-sensing nuclear receptor known for trans-activating liver genes involved in drug metabolism and transport, and more recently implicated in energy metabolism. The gut microbiota can modulate the host xenobiotic biotransformation and contribute to the development of obesity. While the male sex confers a higher risk for NAFLD than women before menopause, the mechanism remains unknown. We hypothesized that the presence of PXR promotes obesity by modifying the gut-liver axis in a sex-specific manner. Male and female C57BL/6 (wild-type/WT) and PXR-knockout (PXR-KO) mice were fed control or high-fat diet (HFD) for 16-weeks. Serum parameters, liver histopathology, transcriptomic profiling, 16S-rDNA sequencing, and bile acid (BA) metabolomics were performed. PXR enhanced HFD-induced weight gain, hepatic steatosis and inflammation especially in males, accompanied by PXR-dependent up-regulation in hepatic genes involved in microbial response, inflammation, oxidative stress, and cancer; PXR-dependent increase in intestinal Firmicutes/Bacteroides ratio (hallmark of obesity) and the pro-inflammatory Lactobacillus, as well as a decrease in the anti-obese Allobaculum and the anti-inflammatory Bifidobacterum, with a PXR-dependent reduction of beneficial BAs in liver. The resistance to NAFLD in females may be explained by PXR-dependent decrease in pro-inflammatory bacteria (Ruminococcus gnavus and Peptococcaceae). In conclusion, PXR exacerbates hepatic steatosis and inflammation accompanied by obesity- and inflammation-prone gut microbiome signature, suggesting that gut microbiome may contribute to PXR-mediated exacerbation of NAFLD.
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