THE EFFECT OF CHRONIC INTERMITTENT HYPOXIA ON HEPATIC INJURY AND MECHANISM IN LEAN MICE AND MICE WITH DIET-INDUCED OBESITY

Background: The purpose of this study was to investigate the effects of CIH on the liver in lean mice and mice with diet-induced obesity (DIO). Methods: Eight-week old C57BL/6J mice were divided into two groups and then exposed to control conditions (room air, n = 16) or CIH (n = 16) for 4 weeks. Each group was divided into two groups again, and then was fed a regular diet or high-fat, high-cholesterol diet for 4 weeks. At the end of the exposure, several genes including hypoxia inducible factor (HIF-1α), vascular endothelial growth factor (VEGF), nuclear factor kappa B (NF-κB), Toll-like receptor 4(TLR4) in liver were examined. Results:There was a significant reduction in body weight in mice exposed to CIH steadily through 4 weeks compared with the control group (P Conclusions: CIH is associated with enhanced expression and signaling events downstream of TLR4 in livers of DIO mice. Our data indicates that CIH causes significant inflammation and liver injury in DIO mice, via TLR4-mediated NF-kB activation. These results suggest that TLR4 may play a critical role in CIH-induced hepatic inflammation.