Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pregnane X receptors (PXRs) and the constitutive androstane receptor (CAR) were initially isolated as nuclear receptors regulating xenobiotic metabolism and elimination, alleviating chemical insults. However, recent works suggest that these xenoreceptors play an endobiotic role in modulating hepatic lipid metabolism. In this study, we show that CAR activators]phenobarbital and 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime] induce the lipogenic gene thyroid hormone-responsive spot 14 protein (THRSP) (or Spot14, S14) expression in human hepatocytes. In addition, we report that treatment of wild-type mice with mCAR activators (phenobarbital and 1,4-Bis[2-(3,5-dichloropyridyloxy)]benzene) efficiently increases thrsp expression, in contrast to CAR null mice. We demonstrate that CAR directly transactivates THRSP promoter through the direct repeat with 4-bp spacer thyroid hormone and PXR response element. Deletion or point mutations within this PXR response element led to a drastic inhibition of CAR-mediated THRSP transactivation. Gel-shift analysis revealed that the CAR/retinoid X receptor complex binds to this element. In conclusion, our results indicate that THRSP gene is a CAR and PXR target gene. Because THRSP expression correlates with lipogenesis and insulin sensitivity, our data suggest that CAR and/or PXR activating drugs and xenobiotics may promote aberrant hepatic de novo lipogenesis leading potentially to fatty liver diseases and insulin resistance.
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PMID:Hepatic expression of thyroid hormone-responsive spot 14 protein is regulated by constitutive androstane receptor (NR1I3). 2018 60

The biological activities and mechanisms of action of individual transoctadecenoic acids (trans-18:1 FA) have not been completely elucidated. We examined the effects of several individual trans-18:1 FA isomers and trans-10, cis-12 conjugated linoleic acid (CLA) on fat synthesis, and expression of lipogenic genes in mammary and liver tissue in lactating mice. From d 6 to 10 postpartum, 30 lactating C57BL/6J mice were randomly assigned to either a control (CTR) diet containing 20 g/kg oleic acid or diets in which the oleic acid was either completely replaced by partially hydrogenated vegetable oil (PHVO), trans-7 18:1 (T7), trans-9 18:1 (T9), or trans-11 18:1 (T11) or partially replaced with 6.66 g/kg trans-10, cis-12 CLA. Milk fat percentage was decreased by CLA (44%), T7 (27%), and PHVO (23%), compared with CTR. In the mammary gland, CLA decreased the expression of genes related to de novo FA synthesis, desaturation, triacylglycerol formation, and transcriptional regulation. PHVO and T7 diets decreased the expression of 1-acylglycerol-3-phosphate O-acyltransferase and thyroid hormone responsive SPOT14 homolog (THRSP) mRNA. In contrast, dietary trans FA (tFA) did not affect hepatic lipogenic gene expression. However, mice fed CLA, T7, and PHVO diets had increased liver weights due to hepatic steatosis. Trans-7 18:1 was extensively desaturated to trans-7, cis-9 CLA in mammary and liver tissues. Dietary trans-7 18:1 could lead to milk fat depression in lactating mice, possibly through its desaturation product trans-7, cis-9 CLA. Also, the differences between the effects of trans-10, cis-12 CLA and other tFA could be attributed to its effects on carbohydrate response element binding protein and PPARgamma, in addition to sterol regulatory element binding transcription factor 1c and THRSP.
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PMID:Dietary trans fatty acid isomers differ in their effects on mammary lipid metabolism as well as lipogenic gene expression in lactating mice. 2022 Feb 7