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The central role is predominantly associated with nutrient homeostasis, while peripherally they play an important role in the synthesis of glucocorticoids (GCs) in response to stress. Pomc mutations are a major risk factor in the development of early\u2010onset childhood obesity in humans. This is attributed primarily to their central effects on melanocortin receptor dysfunction leading to hyperphagia and reduced energy expenditure, while the peripheral mechanism contributing to obesity has largely been unexplored. Here, we tested the hypothesis that Pomc mutation\u2010mediated adrenal insufficiency and the associated changes in GC signaling contribute to postnatal adiposity using zebrafish as a model. We generated a ubiquitous Pomc knockout zebrafish that mimicked the mammalian mutant phenotype of adrenal insufficiency and enhanced adiposity. The loss of Pomc inhibited stress\u2010induced cortisol production and reprogrammed GC signaling by reducing glucocorticoid receptor responsiveness, whereas the mineralocorticoid receptor (Mr) signaling was enhanced. Larval feeding led to enhanced growth and adipogenesis in the Pomc mutants, and this was inhibited by eplerenone, an Mr antagonist. Altogether, our results underscore a key role for Mr signaling in early developmental adipogenesis and a possible target for therapeutic intervention for early\u2010onset childhood obesity due to Pomc dysfunction.<\/jats:p>","DOI":"10.1002\/jcp.31428","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T05:25:17Z","timestamp":1725600317000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Mineralocorticoid receptor activates postnatal adiposity in zebrafish lacking proopiomelanocortin"],"prefix":"10.1002","volume":"239","author":[{"given":"Jithine J.","family":"Rajeswari","sequence":"first","affiliation":[{"name":"Department of Biological Sciences University of Calgary Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin","family":"Faught","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Calgary 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