Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nuclear receptors pregnane X receptor (PXR, or NR1I2) and constitutive androstane receptor (CAR, or NR1I3) were originally identified as xenosensors that regulate the expression of Phase I and Phase II drug-metabolizing enzymes and transporters. Recent results suggest that PXR and CAR also have important endobiotic roles in energy metabolism by affecting the metabolism of fatty acids, lipids and glucose. PXR and CAR exert their effects on energy metabolism through direct gene regulation or through crosstalk with other transcriptional regulators. This review focuses on the roles of CAR and PXR in energy metabolism and offers a perspective on whether PXR and CAR represent novel therapeutic targets for the management of metabolic syndrome.
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PMID:PXR and CAR in energy metabolism. 1959 10

This snapshot reviews the current state of knowledge on genetic variants of nuclear receptors (NRs) involved in regulating various aspects of liver metabolism. Interindividual differences in responses to diet and other 'in-' and environmental stressors can be caused by variants in components of the NR regulatory gene network. We recapitulate recent evidence for the application of NRs in genetic diagnosis of monogenic liver disease. Genetic analysis of multifactorial liver diseases, such as nonalcoholic fatty liver disease and diabetes mellitus, pinpoints key players in disease predisposition and progression. In particular, NR1H4 variants have been associated with intrahepatic cholestasis of pregnancy and gallstone disease. Other examples include studies of NR1I2 and NR1I3 polymorphisms in patients with drug-induced liver injury and NR5A2 variation in cholangiocarcinoma. Associations of NR gene variants have been identified in patients with dyslipidemia and other metabolic syndrome-associated traits by genome-wide studies. Evidence from these analyses confirms a role for NR variation in common diseases, linking regulatory networks to complex and variable phenotypes. These new insights into the impact of NR variants offer perspectives for their future use in diagnosis and treatment of common diseases.
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PMID:Nuclear receptor variants in liver disease. 2604 77

The pregnane X receptor (PXR) (PXR/NR1I3) and constitutive androstane receptor (CAR) (CAR/NR1I2) members of the nuclear receptor (NR) superfamily of ligand-regulated transcription factors are well-characterized mediators of xenobiotic and endocrine-disrupting chemical signaling. The Nuclear Receptor Signaling Atlas maintains a growing library of transcriptomic datasets involving perturbations of NR signaling pathways, many of which involve perturbations relevant to PXR and CAR xenobiotic signaling. Here, we generated a reference transcriptome based on the frequency of differential expression of genes across 159 experiments compiled from 22 datasets involving perturbations of CAR and PXR signaling pathways. In addition to the anticipated overrepresentation in the reference transcriptome of genes encoding components of the xenobiotic stress response, the ranking of genes involved in carbohydrate metabolism and gonadotropin action sheds mechanistic light on the suspected role of xenobiotics in metabolic syndrome and reproductive disorders. Gene Set Enrichment Analysis showed that although acetaminophen, chlorpromazine, and phenobarbital impacted many similar gene sets, differences in direction of regulation were evident in a variety of processes. Strikingly, gene sets representing genes linked to Parkinson's, Huntington's, and Alzheimer's diseases were enriched in all 3 transcriptomes. The reference xenobiotic transcriptome will be supplemented with additional future datasets to provide the community with a continually updated reference transcriptomic dataset for CAR- and PXR-mediated xenobiotic signaling. Our study demonstrates how aggregating and annotating transcriptomic datasets, and making them available for routine data mining, facilitates research into the mechanisms by which xenobiotics and endocrine-disrupting chemicals subvert conventional NR signaling modalities.
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PMID:Research Resource: A Reference Transcriptome for Constitutive Androstane Receptor and Pregnane X Receptor Xenobiotic Signaling. 2740 25