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Sex differences in nuclear receptor-regulated liver metabolic pathways
Authors:Gianpaolo RandoWalter Wahli
Institution:
  • Center for Integrative Genomics and National Research Center Frontiers in Genetics, University of Lausanne, Switzerland
  • 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.
    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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