Chen Liya, Wang Yao, Zheng Weikun, Zhang Hu, Sun Yan, Chen Yiping, Liu Qi
Department of Pediatric Infectious Disease, Wenzhou, China.
The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Front Pharmacol. 2023 Feb 15;14:1097641. doi: 10.3389/fphar.2023.1097641. eCollection 2023.
The high prevalence of non-alcoholic fatty liver disease (NAFLD) in the world raises an important concern for human health. The western diet containing high fat and fructose is the risk factor for NAFLD development. Intermittent hypoxia (IH), known as the basis of obstructive sleep apnea (OSA), normally is correlated with impaired liver function. However, the role of IH in liver injury prevention has been revealed by many other studies based on the different IH paradigms. The current study, therefore, tests the impact of IH on the liver of high-fat and high-fructose diet (HFHFD) fed mice. Mice were exposed to IH (2 min cycle, FiO 8% for 20 s, FiO 20.9% for 100 s; 12 h/day) or intermittent air (FiO 20.9%) for 15 weeks, with normal diet (ND) or high-fat and high-fructose diet (HFHFD). Indices of liver injury and metabolism were measured. IH causes no overt liver injury in mice fed an ND. However, HFHFD-induced lipid accumulation, lipid peroxidation, neutrophil infiltration, and apoptotic process were significantly attenuated by IH exposure. Importantly, IH exposure altered bile acids composition and shifted the hepatic bile acids towards FXR agonism, which was involved in the protection of IH against HFHFD. These results support that the IH pattern in our model prevents liver injury from HFHFD in experimental NAFLD.
非酒精性脂肪性肝病（NAFLD）在全球的高患病率引发了对人类健康的重要关注。富含高脂肪和果糖的西方饮食是NAFLD发展的风险因素。间歇性缺氧（IH），作为阻塞性睡眠呼吸暂停（OSA）的基础，通常与肝功能受损相关。然而，基于不同的IH模式，许多其他研究揭示了IH在预防肝损伤中的作用。因此，本研究测试了IH对高脂高果糖饮食（HFHFD）喂养小鼠肝脏的影响。将小鼠暴露于IH（2分钟周期，FiO₂ 8%持续20秒，FiO₂ 20.9%持续100秒；每天12小时）或间歇性空气（FiO₂ 20.9%）中15周，同时给予正常饮食（ND）或高脂高果糖饮食（HFHFD）。测量肝损伤和代谢指标。在喂食ND的小鼠中，IH不会引起明显的肝损伤。然而，IH暴露显著减轻了HFHFD诱导的脂质积累、脂质过氧化、中性粒细胞浸润和凋亡过程。重要的是，IH暴露改变了胆汁酸组成，并使肝脏胆汁酸向FXR激动作用转变，这参与了IH对HFHFD的保护作用。这些结果支持我们模型中的IH模式可预防实验性NAFLD中HFHFD引起的肝损伤。
