Reduction of intestinal RIPK1 ameliorates HFD-induced metabolic disorders in female mice
Summary: 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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422500166X |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823856714045194240 |
|---|---|
| author | Ye Yuan Xiaomin Hu Chunguang Guo Yihua Xu Shihan Li Wei Wen Xinli Hu Fanxin Zeng Weiyi Cui Wenli Chen Xueting Sun Ning Hou Jue Wang Rui-Ping Xiao Xiuqin Zhang |
| author_facet | Ye Yuan Xiaomin Hu Chunguang Guo Yihua Xu Shihan Li Wei Wen Xinli Hu Fanxin Zeng Weiyi Cui Wenli Chen Xueting Sun Ning Hou Jue Wang Rui-Ping Xiao Xiuqin Zhang |
| author_sort | Ye Yuan |
| collection | DOAJ |
| description | Summary: 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 (Ripk1) intestine-specific heterozygous knockout mice (Ripk1IEC+/−) 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 Ripk1IEC+/− 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 Ripk1IEC+/− 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. |
| format | Article |
| id | doaj-art-0c868d2689ac459ca2ebc3577478946a |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-0c868d2689ac459ca2ebc3577478946a2025-02-12T05:31:39ZengElsevieriScience2589-00422025-02-01282111906Reduction of intestinal RIPK1 ameliorates HFD-induced metabolic disorders in female miceYe Yuan0Xiaomin Hu1Chunguang Guo2Yihua Xu3Shihan Li4Wei Wen5Xinli Hu6Fanxin Zeng7Weiyi Cui8Wenli Chen9Xueting Sun10Ning Hou11Jue Wang12Rui-Ping Xiao13Xiuqin Zhang14Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China; National Biomedical Imaging Center, Peking University, Beijing 100871, ChinaInstitute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, ChinaInstitute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, ChinaInstitute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, ChinaInstitute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, ChinaInstitute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China; PKU-Nanjing Institute of Translational Medicine, Nanjing 211800, ChinaInstitute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, ChinaInstitute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Department of Clinical Research Center, Dazhou Central Hospital, Dazhou 635000, ChinaInstitute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, ChinaInstitute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, ChinaInstitute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, ChinaInstitute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, ChinaInstitute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, ChinaInstitute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China; State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking-Tsinghua Center for Life Sciences, Beijing 100871, China; Corresponding authorInstitute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China; National Biomedical Imaging Center, Peking University, Beijing 100871, China; Corresponding authorSummary: 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 (Ripk1) intestine-specific heterozygous knockout mice (Ripk1IEC+/−) 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 Ripk1IEC+/− 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 Ripk1IEC+/− 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.http://www.sciencedirect.com/science/article/pii/S258900422500166XPhysiologyPathophysiology |
| spellingShingle | Ye Yuan Xiaomin Hu Chunguang Guo Yihua Xu Shihan Li Wei Wen Xinli Hu Fanxin Zeng Weiyi Cui Wenli Chen Xueting Sun Ning Hou Jue Wang Rui-Ping Xiao Xiuqin Zhang Reduction of intestinal RIPK1 ameliorates HFD-induced metabolic disorders in female mice iScience Physiology Pathophysiology |
| title | Reduction of intestinal RIPK1 ameliorates HFD-induced metabolic disorders in female mice |
| title_full | Reduction of intestinal RIPK1 ameliorates HFD-induced metabolic disorders in female mice |
| title_fullStr | Reduction of intestinal RIPK1 ameliorates HFD-induced metabolic disorders in female mice |
| title_full_unstemmed | Reduction of intestinal RIPK1 ameliorates HFD-induced metabolic disorders in female mice |
| title_short | Reduction of intestinal RIPK1 ameliorates HFD-induced metabolic disorders in female mice |
| title_sort | reduction of intestinal ripk1 ameliorates hfd induced metabolic disorders in female mice |
| topic | Physiology Pathophysiology |
| url | http://www.sciencedirect.com/science/article/pii/S258900422500166X |
| work_keys_str_mv | AT yeyuan reductionofintestinalripk1ameliorateshfdinducedmetabolicdisordersinfemalemice AT xiaominhu reductionofintestinalripk1ameliorateshfdinducedmetabolicdisordersinfemalemice AT chunguangguo reductionofintestinalripk1ameliorateshfdinducedmetabolicdisordersinfemalemice AT yihuaxu reductionofintestinalripk1ameliorateshfdinducedmetabolicdisordersinfemalemice AT shihanli reductionofintestinalripk1ameliorateshfdinducedmetabolicdisordersinfemalemice AT weiwen reductionofintestinalripk1ameliorateshfdinducedmetabolicdisordersinfemalemice AT xinlihu reductionofintestinalripk1ameliorateshfdinducedmetabolicdisordersinfemalemice AT fanxinzeng reductionofintestinalripk1ameliorateshfdinducedmetabolicdisordersinfemalemice AT weiyicui reductionofintestinalripk1ameliorateshfdinducedmetabolicdisordersinfemalemice AT wenlichen reductionofintestinalripk1ameliorateshfdinducedmetabolicdisordersinfemalemice AT xuetingsun reductionofintestinalripk1ameliorateshfdinducedmetabolicdisordersinfemalemice AT ninghou reductionofintestinalripk1ameliorateshfdinducedmetabolicdisordersinfemalemice AT juewang reductionofintestinalripk1ameliorateshfdinducedmetabolicdisordersinfemalemice AT ruipingxiao reductionofintestinalripk1ameliorateshfdinducedmetabolicdisordersinfemalemice AT xiuqinzhang reductionofintestinalripk1ameliorateshfdinducedmetabolicdisordersinfemalemice |