Exercise training decreases gene expression of endo- and xeno-sensors in rat small intestine

The purpose of the study was to test the hypothesis that gene expression of members of the nuclear receptor (NR) superfamily known to act as endo- and xeno-sensors is reduced in the ileum of exercise-trained (Tr) rats. Healthy female rats were either treadmill-trained for 8 weeks, 5 times/week, or remained sedentary (Sed). Training resulted in a significant (p < 0.05) decrease in plasma free fatty acid (0.18 ± 0.01 to 0.15 ± 0.01 mmol/L) and glycerol (24.8 ± 0.8 to 18.7 ± 0.8 mg/L) concentrations. Gene expressions of NRs farnesoid X receptor (FXR; p < 0.05), liver X receptor (LXR; p < 0.05), pregnane X receptor (PXR; p < 0.01), and retinoid X receptor (RXR; p < 0.06) were reduced in the ileum of Tr compared with Sed animals. Tr was also associated with a reduction (p < 0.05) in gene expression of FXR downstream heterodimeric organite solute transporters α (OSTα) and β (OSTβ) involved in the transport of bile acids, LXR downstream genes heterodimeric ATP-binding cassette transporters (ABCG5/G8) involved in transport of absorbed cholesterol back to the lumen, and Niemann-Pick C1-like 1 (NPC1L1) involved in cholesterol absorption. These data indicate that exercise training lowers the expression of molecules involved in the defense system of the ileum against endobiotic and xenobiotic insults under normal conditions, thus, suggesting that regular exercise contributes to the intestinal maintenance of cholesterol and bile acid homeostasis.