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While many factors impacting central regulation of feeding behavior have been established, the role of microRNAs in this process is poorly understood. Utilizing unique mouse models, we demonstrate that miR-33 plays a critical role in the regulation of AgRP neurons, and that loss of miR-33 leads to increased feeding, obesity, and metabolic dysfunction in mice. These effects include the regulation of multiple miR-33 target genes involved in mitochondrial biogenesis and fatty acid metabolism. Our findings elucidate a key regulatory pathway regulated by a non-coding RNA that impacts hunger by controlling multiple bioenergetic processes associated with the activation of AgRP neurons, providing alternative therapeutic approaches to modulate feeding behavior and associated metabolic diseases.<\/jats:p>","DOI":"10.1038\/s41467-024-46427-0","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T13:01:49Z","timestamp":1709902909000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["microRNA-33 controls hunger signaling in hypothalamic AgRP neurons"],"prefix":"10.1038","volume":"15","author":[{"given":"Nathan L.","family":"Price","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7263-6767","authenticated-orcid":false,"given":"Pablo","family":"Fern\u00e1ndez-Tussy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Varela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3541-2190","authenticated-orcid":false,"given":"Magdalena P.","family":"Cardelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5366-9846","authenticated-orcid":false,"given":"Marya","family":"Shanabrough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binod","family":"Aryal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3354-2442","authenticated-orcid":false,"given":"Rafael","family":"de Cabo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4549-2953","authenticated-orcid":false,"given":"Yajaira","family":"Su\u00e1rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7522-4602","authenticated-orcid":false,"given":"Tamas L.","family":"Horvath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3950-1924","authenticated-orcid":false,"given":"Carlos","family":"Fern\u00e1ndez-Hernando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,8]]},"reference":[{"key":"46427_CR1","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1161\/ATVBAHA.112.300144","volume":"33","author":"C Fernandez-Hernando","year":"2013","unstructured":"Fernandez-Hernando, C., Ramirez, C. 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