دورية أكاديمية
Hepatic IRE1α-XBP1 signaling promotes GDF15-mediated anorexia and body weight loss in chemotherapy.
| العنوان: | Hepatic IRE1α-XBP1 signaling promotes GDF15-mediated anorexia and body weight loss in chemotherapy. |
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| المؤلفون: | Tang Y; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University , Hangzhou, China.; Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine of Zhejiang Province, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province , Hangzhou, China., Yao T; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University , Hangzhou, China.; Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine of Zhejiang Province, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province , Hangzhou, China.; College of Life Sciences, Zhejiang Chinese Medical University , Hangzhou, China., Tian X; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University , Hangzhou, China.; Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine of Zhejiang Province, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province , Hangzhou, China.; College of Life Sciences, Zhejiang Chinese Medical University , Hangzhou, China., Xia X; Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine of Zhejiang Province, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province , Hangzhou, China.; College of Life Sciences, Zhejiang Chinese Medical University , Hangzhou, China., Huang X; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University , Hangzhou, China., Qin Z; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University , Hangzhou, China., Shen Z; Department of Coloproctology, Hangzhou Third People's Hospital, Hangzhou, China., Zhao L; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University , Hangzhou, China., Zhao Y; Division of Life Sciences and Medicine, Department of Endocrinology, Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of China, Hefei, China., Diao B; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University , Hangzhou, China., Ping Y; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University , Hangzhou, China., Zheng X; Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine of Zhejiang Province, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province , Hangzhou, China., Xu Y; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University , Hangzhou, China., Chen H; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University , Hangzhou, China., Qian T; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Ma T; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Zhou B; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences , Shanghai, China., Xu S; Division of Life Sciences and Medicine, Department of Endocrinology, Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of China, Hefei, China., Zhou Q; Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Liu Y; Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Frontier Science Center for Immunology and Metabolism, The Institute for Advanced Studies, Wuhan University , Wuhan, China., Shao M; CAS Key Laboratory of Molecular Virology and Immunology, The Center for Microbes, Development, and Health, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences , Shanghai, China., Chen W; Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine of Zhejiang Province, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province , Hangzhou, China.; College of Life Sciences, Zhejiang Chinese Medical University , Hangzhou, China., Shan B; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University , Hangzhou, China.; Cancer Center, Zhejiang University , Hangzhou, China., Wu Y; Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine of Zhejiang Province, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province , Hangzhou, China.; College of Life Sciences, Zhejiang Chinese Medical University , Hangzhou, China. |
| المصدر: | The Journal of experimental medicine [J Exp Med] 2024 Jul 01; Vol. 221 (7). Date of Electronic Publication: 2024 May 02. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 2985109R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-9538 (Electronic) Linking ISSN: 00221007 NLM ISO Abbreviation: J Exp Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Rockefeller University Press |
| مواضيع طبية MeSH: | Anorexia*/chemically induced , Anorexia*/metabolism , Doxorubicin*/adverse effects , Endoribonucleases*/metabolism , Endoribonucleases*/genetics , Growth Differentiation Factor 15*/adverse effects , Growth Differentiation Factor 15*/genetics , Growth Differentiation Factor 15*/metabolism , Liver*/metabolism , Liver*/drug effects , Liver*/pathology , Protein Serine-Threonine Kinases*/metabolism , Protein Serine-Threonine Kinases*/genetics , Weight Loss*/drug effects , X-Box Binding Protein 1*/metabolism , X-Box Binding Protein 1*/genetics, Animals ; Humans ; Mice ; Antineoplastic Agents/adverse effects ; Cisplatin/adverse effects ; Mice, Inbred C57BL ; Signal Transduction/drug effects ; Unfolded Protein Response/drug effects |
| مستخلص: | Platinum-based chemotherapy drugs can lead to the development of anorexia, a detrimental effect on the overall health of cancer patients. However, managing chemotherapy-induced anorexia and subsequent weight loss remains challenging due to limited effective therapeutic strategies. Growth differentiation factor 15 (GDF15) has recently gained significant attention in the context of chemotherapy-induced anorexia. Here, we report that hepatic GDF15 plays a crucial role in regulating body weight in response to chemo drugs cisplatin and doxorubicin. Cisplatin and doxorubicin treatments induce hepatic Gdf15 expression and elevate circulating GDF15 levels, leading to hunger suppression and subsequent weight loss. Mechanistically, selective activation by chemotherapy of hepatic IRE1α-XBP1 pathway of the unfolded protein response (UPR) upregulates Gdf15 expression. Genetic and pharmacological inactivation of IRE1α is sufficient to ameliorate chemotherapy-induced anorexia and body weight loss. These results identify hepatic IRE1α as a molecular driver of GDF15-mediated anorexia and suggest that blocking IRE1α RNase activity offers a therapeutic strategy to alleviate the adverse anorexia effects in chemotherapy. (© 2024 Tang et al.) |
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| معلومات مُعتمدة: | 2022YFA1104102 National Key Research and Development Program of China; 32371235 National Natural Science Foundation of China; 226-2023-00061 Fundamental Research Funds for the Central Universities; LQ23H160003 Natural Science Funding of Zhejiang Province; Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents; 22140903200 Shanghai Municipal Science and Technology; GZY-ZJ-SY-2402 State Administration of Traditional Chinese Medicine; YSZX2401 Zhejiang Provincial Department of Science and Technology; 2022R01002 Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang |
| المشرفين على المادة: | 0 (ERN1 protein, human) 0 (Ern1 protein, mouse) 0 (GDF15 protein, human) 0 (Gdf15 protein, mouse) 0 (XBP1 protein, human) 0 (Xbp1 protein, mouse) |
| تواريخ الأحداث: | Date Created: 20240502 Date Completed: 20240502 Latest Revision: 20240517 |
| رمز التحديث: | 20240518 |
| مُعرف محوري في PubMed: | PMC11070642 |
| DOI: | 10.1084/jem.20231395 |
| PMID: | 38695876 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1540-9538 |
|---|---|
| DOI: | 10.1084/jem.20231395 |