Division of Nutritional Sciences, University of Illinois Urbana Champaign, Urbana, IL, United States of America.
Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL, United States of America.
Biochim Biophys Acta Mol Basis Dis. 2021 Nov 1;1867(11):166211. doi: 10.1016/j.bbadis.2021.166211. Epub 2021 Jul 14.
Sex differences in physiology are noted in clinical and animal studies. However, mechanisms underlying these observed differences between males and females remain elusive. Nuclear receptors control a wide range of physiological pathways and are expressed in the gastrointestinal tract, including the mouth, stomach, liver and intestine. We investigated the literature pertaining to ER, AR, FXR, and PPAR regulation and highlight the sex differences in nutrient metabolism along the digestive system. We chose these nuclear receptors based on their metabolic functions, and hormonal actions. Intriguingly, we noted an overlap in target genes of ER and FXR that modulate mucosal integrity and GLP-1 secretion, whereas overlap in target genes of PPARα with ER and AR modulate lipid metabolism. Sex differences were seen not only in the basal expression of nuclear receptors, but also in activation as their endogenous ligand concentrations fluctuate depending on nutrient availability. Finally, in this review, we speculate that interactions between the nuclear receptors may influence overall metabolic decisions in the gastrointestinal tract in a sex-specific manner.
在临床和动物研究中都注意到了生理学上的性别差异。然而，男性和女性之间观察到的这些差异的潜在机制仍然难以捉摸。核受体控制着广泛的生理途径，在胃肠道中表达，包括口腔、胃、肝和肠。我们调查了与 ER、AR、FXR 和 PPAR 调节相关的文献，并强调了沿消化系统的营养代谢中的性别差异。我们根据这些核受体的代谢功能和激素作用选择了这些核受体。有趣的是，我们注意到 ER 和 FXR 的靶基因重叠，这些基因调节粘膜完整性和 GLP-1 分泌，而 ER 和 AR 的 PPARα 靶基因重叠调节脂质代谢。不仅在核受体的基础表达中存在性别差异，而且在其内源性配体浓度根据营养物质的可用性而波动时，激活也存在性别差异。最后，在这篇综述中，我们推测核受体之间的相互作用可能以性别特异性的方式影响胃肠道的整体代谢决策。
