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Collectively, these peptides ensure that physiology (e.g., fat storage, fluid balance) and behavior (e.g., feeding, sleep) are coordinated with environmental factors such as nutrient quantity and quality. Despite notable sex differences in physiology and behavior, it remains unclear whether the regulation and function of these EE cell-derived factors are shared between males and females. Given that recent data identified sex-biased physiological effects of two EE cell-derived hormones on\n                    <jats:italic>Drosophila<\/jats:italic>\n                    food intake and energy mobilization, we performed a detailed characterization of these hormones in male and female flies. Despite an overall male bias in mRNA levels of\n                    <jats:italic>AstA<\/jats:italic>\n                    ,\n                    <jats:italic>AstC<\/jats:italic>\n                    ,\n                    <jats:italic>Tk<\/jats:italic>\n                    ,\n                    <jats:italic>NPF<\/jats:italic>\n                    , and\n                    <jats:italic>Dh31<\/jats:italic>\n                    in whole-body and head samples, we observed a strong female bias in mRNA levels of\n                    <jats:italic>AstC<\/jats:italic>\n                    ,\n                    <jats:italic>Tk<\/jats:italic>\n                    , and\n                    <jats:italic>NPF<\/jats:italic>\n                    in the gut. To determine whether this sex-biased regulation was physiologically significant, we monitored triglyceride levels in flies with gut-specific knock-down of EE cell-derived hormones. In 5-day-old flies, knock-down of EE cell-derived\n                    <jats:italic>AstC<\/jats:italic>\n                    significantly reduced fat storage in females with no effect in males, whereas knock-down of EE cell-derived\n                    <jats:italic>Tk<\/jats:italic>\n                    produced a non-significant trend toward reduced fat storage in females. These female-specific effects on fat storage were reproduced in flies with neuron-specific knock-down of the AstC (\n                    <jats:italic>AstC-R2<\/jats:italic>\n                    ) and Tk receptors (\n                    <jats:italic>TkR99D<\/jats:italic>\n                    ). Together, these data uncover strongly sex-biased regulation of EE cell-derived hormones and show that gut-specific knock-down of at least one of these hormones had a female-specific effect on body fat.\n                  <\/jats:p>","DOI":"10.7554\/elife.109426","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T14:30:19Z","timestamp":1766413819000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.109426","source":"Crossref","is-referenced-by-count":0,"title":["Sex-biased expression of enteroendocrine cell-derived hormones contributes to higher fat storage in Drosophila females"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6808-6662","authenticated-orcid":true,"given":"Puja","family":"Biswas","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03rmrcq20","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Cellular and Physiological Sciences, Life Sciences Institute, The 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