Gene Expression Profiling Reveals that PXR Activation Inhibits Hepatic PPARα Activity and Decreases FGF21 Secretion in Male C57Bl6/J Mice

Barretto, Sharon Ann; Lasserre, Frédèric; Fougerat, Anne; Smith, Lorraine; Fougeray, Tiffany; Lukowicz, Céline; Polizzi, Arnaud; Smati, Sarra; Régnier, Marion; Naylies, Claire; Bétoulières, Colette; Lippi, Yannick; Guillou, Hervé; Loiseau, Nicolas; Gamet-Payrastre, Laurence; Mselli-Lakhal, Laïla; Ellero‐Simatos, Sandrine

doi:10.3390/ijms20153767

Cited by 14 publications

(13 citation statements)

References 46 publications

(61 reference statements)

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“…Intriguingly, the suppressive effect of PFOA on plasma cholesterol was magnified in the PPARα −/− mice. Taking into account the increased sensitivity to PXR activation in the PPARα −/− mice and considering that PXR activation lowers plasma cholesterol, it can be speculated that PFOA reduces plasma cholesterol via PXR [ 79 ]. Concerning NEFA, plasma levels were decreased by high-dose PFOA in the wildtype and PPARα −/− mice, suggesting that the effect is independent of PPARα.…”

Section: Discussionmentioning

confidence: 99%

Exposure to low-dose perfluorooctanoic acid promotes hepatic steatosis and disrupts the hepatic transcriptome in mice

Attema¹,

Janssen²,

Rijkers³

et al. 2022

Molecular Metabolism

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Section: Discussionmentioning

confidence: 99%

Exposure to low-dose perfluorooctanoic acid promotes hepatic steatosis and disrupts the hepatic transcriptome in mice

Attema¹,

Janssen²,

Rijkers³

et al. 2022

Molecular Metabolism

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“…These findings support the favorable impact of lingonberry-induced increase in Cyp2c29 expression found in the present study. Cyp2c55 (also increased by lingonberry supplementation) is a target gene for nuclear receptor pregnane X (PXR), and is related to retinol metabolism and 19-HETE synthesis from arachidonic acid [95][96][97].…”

Section: Discussionmentioning

confidence: 99%

Effects of Lingonberry (Vaccinium vitis-idaea L.) Supplementation on Hepatic Gene Expression in High-Fat Diet Fed Mice

et al. 2021

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The prevalence of nonalcoholic fatty liver disease (NAFLD) is growing worldwide in association with Western-style diet and increasing obesity. Lingonberry (Vaccinium vitis-idaea L.) is rich in polyphenols and has been shown to attenuate adverse metabolic changes in obese liver. This paper investigated the effects of lingonberry supplementation on hepatic gene expression in high-fat diet induced obesity in a mouse model. C57BL/6N male mice were fed for six weeks with either a high-fat (HF) or low-fat (LF) diet (46% and 10% energy from fat, respectively) or HF diet supplemented with air-dried lingonberry powder (HF + LGB). HF diet induced a major phenotypic change in the liver, predominantly affecting genes involved in inflammation and in glucose and lipid metabolism. Lingonberry supplementation prevented the effect of HF diet on an array of genes (in total on 263 genes) associated particularly with lipid or glucose metabolic process (such as Mogat1, Plin4, Igfbp2), inflammatory/immune response or cell migration (such as Lcn2, Saa1, Saa2, Cxcl14, Gcp1, S100a10) and cell cycle regulation (such as Cdkn1a, Tubb2a, Tubb6). The present results suggest that lingonberry supplementation prevents HF diet-induced adverse changes in the liver that are known to predispose the development of NAFLD and its comorbidities. The findings encourage carrying out human intervention trials to confirm the results, with the aim of recommending the use of lingonberries as a part of healthy diet against obesity and its hepatic and metabolic comorbidities.

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“…The widely used anti-inflammatory drug hypocretin has also been reported as an agonist of PXR, the activation of PXR is followed by upregulation of the downstream proteins CYP3A11, CYP2B10, and organic anion transporter 2 (OATP2), which can also stimulate nuclear migration of YAP, leading to lipid accumulation (10). In addition to the accumulation of triglycerides in the liver of transgenic mice, PXR activation down-regulates hepatic PPARa activity and fibroblast growth factor 12 (FGF21) circulation, which could participate in the pleiotropic role of PXR in energy homeostasis (90).…”

Section: Pxr In Lipid Metabolismmentioning

confidence: 99%

The role of pregnane X receptor (PXR) in substance metabolism

Luo

Ren

et al. 2022

Front. Endocrinol.

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As a member of the nuclear receptor (NR) superfamily, pregnane X receptor (PXR; NR1I2) is a ligand-activated transcription factor that plays a crucial role in the metabolism of xenobiotics and endobiotics in mammals. The tissue distribution of PXR is parallel to its function with high expression in the liver and small intestine and moderate expression in the kidney, stomach, skin, and blood-brain barrier, which are organs and tissues in frequent contact with xenobiotics. PXR was first recognized as an exogenous substance receptor regulating metabolizing enzymes and transporters and functioning in detoxification and drug metabolism in the liver. However, further research revealed that PXR acts as an equally important endogenous substance receptor in the metabolism and homeostasis of endogenous substances. In this review, we summarized the functions of PXR in metabolism of different substances such as glucose, lipid, bile acid, vitamin, minerals, and endocrines, and also included insights of the application of PXR ligands (drugs) in specific diseases.

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Gene Expression Profiling Reveals that PXR Activation Inhibits Hepatic PPARα Activity and Decreases FGF21 Secretion in Male C57Bl6/J Mice

Cited by 14 publications

References 46 publications

Exposure to low-dose perfluorooctanoic acid promotes hepatic steatosis and disrupts the hepatic transcriptome in mice

Exposure to low-dose perfluorooctanoic acid promotes hepatic steatosis and disrupts the hepatic transcriptome in mice

Effects of Lingonberry (Vaccinium vitis-idaea L.) Supplementation on Hepatic Gene Expression in High-Fat Diet Fed Mice

The role of pregnane X receptor (PXR) in substance metabolism

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