Sex differences in nuclear receptor-regulated liver metabolic pathways |
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Authors: | Gianpaolo RandoWalter Wahli |
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Institution: | Center for Integrative Genomics and National Research Center Frontiers in Genetics, University of Lausanne, Switzerland |
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Abstract: | Liver metabolism is markedly sex-dimorphic; accordingly, the prevalence of liver diseases is different between sexes. The superfamily of nuclear receptors (NRs) governs the proper expression of key liver metabolism genes by sensing lipid-soluble hormones and dietary lipids. When the expression of those genes is deregulated, disease development is favored. However, we lack a comprehensive picture of the differences between NR actions in males and females. Here, we reviewed explorative studies that assessed NR functions in both sexes, and we propose a first map of sex-dimorphic NR expression in the liver. Our analysis suggested that NRs in the female liver exhibited cross-talk with more liver-protective potential than NRs in male liver. This study provides empirical support to the hypothesis that women are more resilient to some liver diseases than men, based on a more compensative NR network. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease. |
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Keywords: | NRs nuclear receptors ER estrogen receptor AR androgen receptor GR glucocorticoid receptor RXR retinoic X receptor LXR liver X receptor PPAR peroxisome proliferator activated receptor TR thyroid hormone receptor PXR pregnane X receptor CAR constitutive androstane receptor |
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