Yuan Ye, Hu Xiaomin, Guo Chunguang, Xu Yihua, Li Shihan, Wen Wei, Hu Xinli, Zeng Fanxin, Cui Weiyi, Chen Wenli, Sun Xueting, Hou Ning, Wang Jue, Xiao Rui-Ping, Zhang Xiuqin
Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China.
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
iScience. 2025 Jan 27;28(2):111906. doi: 10.1016/j.isci.2025.111906. eCollection 2025 Feb 21.
In modern society, excessive nutrient intake from food is a major factor contributing to the development of a series of metabolic disorders and cardiovascular diseases. Further investigation of the mechanisms underlying nutrient absorption in the intestine will help to better understand and develop preventive or therapeutic strategies. In this study, using receptor-interacting protein kinase 1 () intestine-specific heterozygous knockout mice ( ) and high-fat diet (HFD)-feeding mouse model, we report that HFD-induced shift in the transcriptional profile of the ileum toward that of the jejunum, characterized by increased expression of jejunal feature genes in the ileum, are attenuated in female mice, but not in males. Accordingly, HFD-induced metabolic disorders, including obesity, impaired glucose tolerance, insulin resistance, and dyslipidemia, are significantly ameliorated in the female mice. These findings demonstrate a new, sex-specific intestinal regulatory mechanism and highlight the critical role of intestinal RIPK1 in regulating HFD-induced metabolic disorders in females.
在现代社会，食物中营养物质摄入过多是导致一系列代谢紊乱和心血管疾病的主要因素。进一步研究肠道营养吸收的潜在机制将有助于更好地理解并制定预防或治疗策略。在本研究中，我们使用受体相互作用蛋白激酶1（RIPK1）肠道特异性杂合敲除小鼠（RIPK1ΔIEC）和高脂饮食（HFD）喂养的小鼠模型，发现HFD诱导的回肠转录谱向空肠转录谱转变（其特征为回肠中十二指肠特征基因表达增加）在RIPK1ΔIEC雌性小鼠中减弱，但在雄性小鼠中未减弱。相应地，HFD诱导的代谢紊乱，包括肥胖、葡萄糖耐量受损、胰岛素抵抗和血脂异常，在RIPK1ΔIEC雌性小鼠中得到显著改善。这些发现揭示了一种新的、性别特异性的肠道调节机制，并突出了肠道RIPK1在调节雌性小鼠HFD诱导的代谢紊乱中的关键作用。
