Reoxygenation improves reduced hypothalamic leptin responsiveness induced by intermittent hypoxia in obese rats
10.12122/j.issn.1673-4254.2024.09.09
- VernacularTitle:复氧改善间歇性缺氧所致的肥胖大鼠下丘脑瘦素反应性降低
- Author:
Menglu DONG
1
;
Tian ZHU
;
Junwen MA
;
Xiaohong DU
;
Yuan FENG
Author Information
1. 南方医科大学南方医院精神心理科(睡眠医学中心),广东 广州 510515
- Keywords:
intermittent hypoxia;
obstructive sleep apnea;
obesity;
leptin;
reoxygenation
- From:
Journal of Southern Medical University
2024;44(9):1696-1703
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the effects of intermittent hypoxia-reoxygenation(IHR)on body weight,diet and water intake,circulating metabolites,and responses to central leptin injection in a rat model of diet-induced obesity(DIO).Methods Rat models of DIO established by 12-week high-fat diet(HFD)feeding were randomized into normoxia group(n=15),intermittent hypoxia group(6％O2,30 cycles/h,8 h/day for 4 weeks;n=15),and IHR group(2 weeks of intermittent hypoxia followed by 2 weeks of reoxygenation;n=15).Body weight,diet and water intake of the rats were recorded,and circulating leptin,IL-6,and Ang-Ⅱ levels were detected.After IHR treatment,the rats received intracerebroventricular injection of 4 μg leptin,and the hypothalamus and liver were taken 1 h later for detecting POMC,FRA-1 and FRA-2 expressions in the hypothalamus using immunohistochemistry,POMC,pSTAT3 and LepR expressions in the hypothalamus using Western blotting,and LepR mRNA expression in the hypothalamus and liver using RT-PCR.Results The rats in intermittent hypoxia group showed significantly increased weight gain,food intake and elevated systemic inflammatory cytokine levels.Intermittent hypoxia obviously inhibited the expression of POMC,lowered the expressions of FRA-1 and pSTAT3,reduced the responsiveness of the rats to exogenous leptin,and downregulated the mRNA and protein expression of LepR.Two weeks of reoxygenation treatment obviously reduced intermittent hypoxia-induced weight gain and metabolic disorder and improved leptin sensitivity of the rats.Conclusion Prolonged intermittent hypoxia impairs hypothalamic leptin signaling by downregulating LepR expression to promote weight gain in obese rats,which can be improved by reoxygenation treatment.
