Hui Chen, Stéphanie Moriceau, Adrien Joseph, Francois Mailliet, Sijing Li, Virginie Tolle, Philibert Duriez, Roland Dardennes, Sylvère Durand, Vincent Carbonnier, Gautier Stoll, Allan Sauvat, Sylvie Lachkar, Fanny Aprahamian, Carolina Alves Costa Silva, Hui Pan, Léa Montégut, Gerasimos Anagnostopoulos, Flavia Lambertucci, Omar Motiño, Uxía Nogueira-Recalde, Mélanie Bourgin, Misha Mao, Yuhong Pan, Alexandra Cerone, Erwan Boedec, Zelia L. Gouveia, Federica Marmorino, Chiara Cremolini, Lisa Derosa, Laurence Zitvogel, Oliver Kepp, Carlos López-Otín, Maria Chiara Maiuri, Franck Perez, Philip Gorwood, Nicolas Ramoz, Franck Oury, Isabelle Martins, Guido Kroemer
{"title":"用于实验性治疗厌食症的 Acyl-CoA 结合蛋白。","authors":"Hui Chen, Stéphanie Moriceau, Adrien Joseph, Francois Mailliet, Sijing Li, Virginie Tolle, Philibert Duriez, Roland Dardennes, Sylvère Durand, Vincent Carbonnier, Gautier Stoll, Allan Sauvat, Sylvie Lachkar, Fanny Aprahamian, Carolina Alves Costa Silva, Hui Pan, Léa Montégut, Gerasimos Anagnostopoulos, Flavia Lambertucci, Omar Motiño, Uxía Nogueira-Recalde, Mélanie Bourgin, Misha Mao, Yuhong Pan, Alexandra Cerone, Erwan Boedec, Zelia L. Gouveia, Federica Marmorino, Chiara Cremolini, Lisa Derosa, Laurence Zitvogel, Oliver Kepp, Carlos López-Otín, Maria Chiara Maiuri, Franck Perez, Philip Gorwood, Nicolas Ramoz, Franck Oury, Isabelle Martins, Guido Kroemer","doi":"10.1126/scitranslmed.adl0715","DOIUrl":null,"url":null,"abstract":"<div >Extracellular acyl-coenzyme A binding protein [ACBP encoded by diazepam binding inhibitor (DBI)] is a phylogenetically ancient appetite stimulator that is secreted in a nonconventional, autophagy-dependent fashion. Here, we show that low ACBP/DBI plasma concentrations are associated with poor prognosis in patients with anorexia nervosa, a frequent and often intractable eating disorder. In mice, anorexia induced by chronic restraint stress (CRS) is accompanied by a reduction in circulating ACBP/DBI concentrations. We engineered a chemical-genetic system for the secretion of ACBP/DBI through a biotin-activatable, autophagy-independent pathway. In transgenic mice expressing this system in hepatocytes, biotin-induced elevations in plasma ACBP/DBI concentrations prevented anorexia induced by CRS or chemotherapeutic agents including cisplatin, doxorubicin, and paclitaxel. ACBP/DBI reversed the CRS or cisplatin-induced increase in plasma lipocalin-2 concentrations and the hypothalamic activation of anorexigenic melanocortin 4 receptors, for which lipocalin-2 is an agonist. Daily intravenous injections of recombinant ACBP/DBI protein or subcutaneous implantation of osmotic pumps releasing recombinant ACBP/DBI mimicked the orexigenic effects of the chemical-genetic system. In conclusion, the supplementation of extracellular and peripheral ACBP/DBI might constitute a viable strategy for treating anorexia.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"16 760","pages":""},"PeriodicalIF":15.8000,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/scitranslmed.adl0715","citationCount":"0","resultStr":"{\"title\":\"Acyl-CoA binding protein for the experimental treatment of anorexia\",\"authors\":\"Hui Chen, Stéphanie Moriceau, Adrien Joseph, Francois Mailliet, Sijing Li, Virginie Tolle, Philibert Duriez, Roland Dardennes, Sylvère Durand, Vincent Carbonnier, Gautier Stoll, Allan Sauvat, Sylvie Lachkar, Fanny Aprahamian, Carolina Alves Costa Silva, Hui Pan, Léa Montégut, Gerasimos Anagnostopoulos, Flavia Lambertucci, Omar Motiño, Uxía Nogueira-Recalde, Mélanie Bourgin, Misha Mao, Yuhong Pan, Alexandra Cerone, Erwan Boedec, Zelia L. Gouveia, Federica Marmorino, Chiara Cremolini, Lisa Derosa, Laurence Zitvogel, Oliver Kepp, Carlos López-Otín, Maria Chiara Maiuri, Franck Perez, Philip Gorwood, Nicolas Ramoz, Franck Oury, Isabelle Martins, Guido Kroemer\",\"doi\":\"10.1126/scitranslmed.adl0715\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div >Extracellular acyl-coenzyme A binding protein [ACBP encoded by diazepam binding inhibitor (DBI)] is a phylogenetically ancient appetite stimulator that is secreted in a nonconventional, autophagy-dependent fashion. Here, we show that low ACBP/DBI plasma concentrations are associated with poor prognosis in patients with anorexia nervosa, a frequent and often intractable eating disorder. In mice, anorexia induced by chronic restraint stress (CRS) is accompanied by a reduction in circulating ACBP/DBI concentrations. We engineered a chemical-genetic system for the secretion of ACBP/DBI through a biotin-activatable, autophagy-independent pathway. In transgenic mice expressing this system in hepatocytes, biotin-induced elevations in plasma ACBP/DBI concentrations prevented anorexia induced by CRS or chemotherapeutic agents including cisplatin, doxorubicin, and paclitaxel. ACBP/DBI reversed the CRS or cisplatin-induced increase in plasma lipocalin-2 concentrations and the hypothalamic activation of anorexigenic melanocortin 4 receptors, for which lipocalin-2 is an agonist. Daily intravenous injections of recombinant ACBP/DBI protein or subcutaneous implantation of osmotic pumps releasing recombinant ACBP/DBI mimicked the orexigenic effects of the chemical-genetic system. In conclusion, the supplementation of extracellular and peripheral ACBP/DBI might constitute a viable strategy for treating anorexia.</div>\",\"PeriodicalId\":21580,\"journal\":{\"name\":\"Science Translational Medicine\",\"volume\":\"16 760\",\"pages\":\"\"},\"PeriodicalIF\":15.8000,\"publicationDate\":\"2024-08-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.science.org/doi/reader/10.1126/scitranslmed.adl0715\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Science Translational Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.science.org/doi/10.1126/scitranslmed.adl0715\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Translational Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.science.org/doi/10.1126/scitranslmed.adl0715","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Acyl-CoA binding protein for the experimental treatment of anorexia
Extracellular acyl-coenzyme A binding protein [ACBP encoded by diazepam binding inhibitor (DBI)] is a phylogenetically ancient appetite stimulator that is secreted in a nonconventional, autophagy-dependent fashion. Here, we show that low ACBP/DBI plasma concentrations are associated with poor prognosis in patients with anorexia nervosa, a frequent and often intractable eating disorder. In mice, anorexia induced by chronic restraint stress (CRS) is accompanied by a reduction in circulating ACBP/DBI concentrations. We engineered a chemical-genetic system for the secretion of ACBP/DBI through a biotin-activatable, autophagy-independent pathway. In transgenic mice expressing this system in hepatocytes, biotin-induced elevations in plasma ACBP/DBI concentrations prevented anorexia induced by CRS or chemotherapeutic agents including cisplatin, doxorubicin, and paclitaxel. ACBP/DBI reversed the CRS or cisplatin-induced increase in plasma lipocalin-2 concentrations and the hypothalamic activation of anorexigenic melanocortin 4 receptors, for which lipocalin-2 is an agonist. Daily intravenous injections of recombinant ACBP/DBI protein or subcutaneous implantation of osmotic pumps releasing recombinant ACBP/DBI mimicked the orexigenic effects of the chemical-genetic system. In conclusion, the supplementation of extracellular and peripheral ACBP/DBI might constitute a viable strategy for treating anorexia.
期刊介绍:
Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research.
The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases.
The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine.
The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.