Sex differences feed into nuclear receptor signaling along the digestive tract

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1867

Article

Dean, Angela E.¹  Reichardt, Francois²  Anakk, Sayeepriyadarshini^1,2,3 

[1] Univ Illinois, Div Nutr Sci, Urbana, IL USA

[2] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL USA

[3] Univ Illinois, Canc Ctr Illinois, Urbana, IL USA

关键词: Nuclear receptors;    Sex differences;    Gastrointestinal tract;    Sex steroids;    Bile acids;   

DOI  :  10.1016/j.bbadis.2021.166211

来源: Elsevier

【 摘 要 】

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 PPARa 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.

【 授权许可】

Free