{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:41:42Z","timestamp":1787510502884,"version":"build-2736575974"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T00:00:00Z","timestamp":1561420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002367","name":"Chinese Academy of Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002367","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["XDA08010405"],"award-info":[{"award-number":["XDA08010405"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31530077"],"award-info":[{"award-number":["31530077"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key R&D Program of China","award":["2018YFD0900205"],"award-info":[{"award-number":["2018YFD0900205"]}]},{"name":"National Key R&D Program of China","award":["2018YFD0900404"],"award-info":[{"award-number":["2018YFD0900404"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The endocrine regulatory roles of the hypothalamic\u2013pituitary\u2013adrenocortical axis on anxiety-like behavior and metabolic status have been found throughout animal taxa. However, the precise effects of the balancing adrenal corticosteroid biosynthesis under the influence of adrenocorticotrophic hormone (ACTH), a pro-opiomelanocortin (POMC)-derived peptide, on animal energy expenditure and somatic growth remain unknown. POMC has also been identified as one of the candidate loci for polycystic ovary syndrome, which features hyperandrogenism and some prevalence of obesity in patients. Here we show that zebrafish lacking functional POMCa exhibit similar phenotypes of stress response and body weight gain but not obesity as observed in mammalian models. In contrast with the impaired anorexigenic signaling cascade of melanocyte-stimulating hormones and leptin, which are responsible for their obesity-prone weight gain observed in various pomc mutant mammals, analyses with our pomca mutant series indicate that ACTH is the key regulator for the phenotype with enhanced somatic growth without obesity in pomca-deficient zebrafish. Hypocortisolism associated with hyperandrogenism has been observed in the pomca-deficient zebrafish, with enhanced activation of mammalian target of rapamycin complex 1; reutilization of amino acids and fatty acid \u03b2-oxidation are observed in the muscle tissue of the pomca-deficient fish. After reducing hyperandrogenism by crossing our pomca mutant fish with a cyp17a1-deficient background, the phenotype of enhanced somatic growth in pomca-deficient fish was no longer observed. Thus, our work also demonstrated that the role of POMCa in stress response seems to be conserved in vertebrates, whereas its effect on adipostasis is unique to teleosts.<\/jats:p>","DOI":"10.1093\/jmcb\/mjz053","type":"journal-article","created":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T17:34:53Z","timestamp":1561052093000},"page":"291-304","source":"Crossref","is-referenced-by-count":46,"title":["Hyperandrogenism in POMCa-deficient zebrafish enhances somatic growth without increasing adiposity"],"prefix":"10.1093","volume":"12","author":[{"given":"Chuang","family":"Shi","sequence":"first","affiliation":[{"name":"State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Lu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Zhai","sequence":"first","affiliation":[{"name":"State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfei","family":"Huang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohui","family":"Shang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyong","family":"Lou","sequence":"first","affiliation":[{"name":"State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongliang","family":"Li","sequence":"first","affiliation":[{"name":"School of Life Sciences, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Jin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangyan","family":"He","sequence":"first","affiliation":[{"name":"State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Du","sequence":"first","affiliation":[{"name":"School of Life Sciences, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfang","family":"Gui","sequence":"first","affiliation":[{"name":"State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhan","family":"Yin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China"},{"name":"The Innovative Academy of Seed Design, Chinese Academy of Sciences, Beijing 100864, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,6,25]]},"reference":[{"key":"2020051804580435900_ref1","doi-asserted-by":"crossref","first-page":"e6463","DOI":"10.1371\/journal.pone.0006463","article-title":"Adrenocorticotropic hormone suppresses gonadotropin-stimulated estradiol release from zebrafish ovarian follicles","volume":"4","author":"Alsop","year":"2009","journal-title":"PLoS One"},{"key":"2020051804580435900_ref2","doi-asserted-by":"crossref","first-page":"T157","DOI":"10.1530\/JME-16-0014","article-title":"60 years of POMC: regulation of feeding and energy homeostasis by \u03b1-MSH","volume":"56","author":"Anderson","year":"2016","journal-title":"J. Mol. Endocrinol."},{"key":"2020051804580435900_ref3","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.fertnstert.2006.10.006","article-title":"Genetic variants in peroxisome proliferator-activated receptor gamma influence insulin resistance and testosterone levels in normal women, but not those with polycystic ovary syndrome","volume":"87","author":"Antoine","year":"2007","journal-title":"Fertil. Steril."},{"key":"2020051804580435900_ref4","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.2337\/diabetes.54.8.2269","article-title":"Proopiomelanocortin-deficient mice are hypersensitive to the adverse metabolic effects of glucocorticoids","volume":"54","author":"Coll","year":"2005","journal-title":"Diabetes"},{"key":"2020051804580435900_ref5","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/S0015-0282(98)00512-3","article-title":"Polymorphism T\u2192C (\u221234 bp) of gene CYP17 promoter in Greek patients with polycystic ovary syndrome","volume":"71","author":"Diamanti-Kandarakis","year":"1999","journal-title":"Fertil. Steril."},{"key":"2020051804580435900_ref6","doi-asserted-by":"crossref","first-page":"T29","DOI":"10.1530\/JME-14-0050","article-title":"Molecular evolution of GPCRs: melanocortin\/melanocortin receptors","volume":"52","author":"Dores","year":"2014","journal-title":"J. Mol. Endocrinol."},{"key":"2020051804580435900_ref7","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.2337\/diab.38.9.1165","article-title":"Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome","volume":"38","author":"Dunaif","year":"1989","journal-title":"Diabetes"},{"key":"2020051804580435900_ref8","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1016\/j.metabol.2008.08.002","article-title":"Polymorphism T\u2192C (\u221234 base pairs) of gene CYP17 promoter in women with polycystic ovary syndrome is associated with increased body weight and insulin resistance: a preliminary study","volume":"57","author":"Echibur\u00fa","year":"2008","journal-title":"Metabolism"},{"key":"2020051804580435900_ref9","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1056\/NEJMra041536","article-title":"Polycystic ovary syndrome","volume":"352","author":"Ehrmann","year":"2005","journal-title":"New Engl. J. 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Metab."},{"key":"2020051804580435900_ref12","first-page":"61","article-title":"Generation and phenotype analysis of zebrafish mutations of obesity-related genes lepr and mc4r","volume":"69","author":"Fei","year":"2017","journal-title":"Sheng Li Xue Bao"},{"key":"2020051804580435900_ref13","doi-asserted-by":"crossref","first-page":"T135","DOI":"10.1530\/JME-15-0257","article-title":"60 years of POMC: adrenal and extra-adrenal functions of ACTH","volume":"56","author":"Gallo-Payet","year":"2016","journal-title":"J. Mol. Endocrinol."},{"key":"2020051804580435900_ref14","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3389\/fendo.2016.00088","article-title":"Depletion of myostatin b promotes somatic growth and lipid metabolism in zebrafish","volume":"7","author":"Gao","year":"2016","journal-title":"Front. 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Bull."},{"key":"2020051804580435900_ref49","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.cmet.2011.12.014","article-title":"AgRP and POMC neurons are hypophysiotropic and coordinately regulate multiple endocrine axes in a larval teleost","volume":"15","author":"Zhang","year":"2012","journal-title":"Cell Metab."}],"container-title":["Journal of Molecular Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jmcb\/advance-article-pdf\/doi\/10.1093\/jmcb\/mjz053\/31588630\/mjz053.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jmcb\/article-pdf\/12\/4\/291\/33224373\/mjz053.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jmcb\/article-pdf\/12\/4\/291\/33224373\/mjz053.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T20:41:39Z","timestamp":1609965699000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jmcb\/article\/12\/4\/291\/5522641"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,25]]},"references-count":49,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,6,25]]},"published-print":{"date-parts":[[2020,5,18]]}},"URL":"https:\/\/doi.org\/10.1093\/jmcb\/mjz053","relation":{},"ISSN":["1759-4685"],"issn-type":[{"value":"1759-4685","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,4]]},"published":{"date-parts":[[2019,6,25]]}}}