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Alliance"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:p>Growth differentiation factor 15 (GDF15) is a mitochondrial stress-induced cytokine that modulates energy balance in an endocrine manner. However, the importance of its brainstem-restricted receptor GDNF family receptor alpha-like (GFRAL) to mediate endocrine GDF15 signaling to the brain upon mitochondrial dysfunction is still unknown. Using a mouse model with muscle-specific mitochondrial dysfunction, we here show that GFRAL is required for activation of systemic energy metabolism via daytime-restricted anorexia but not responsible for muscle wasting. We further find that muscle mitochondrial stress response involves a GFRAL-dependent induction of hypothalamic corticotropin-releasing hormone, without elevated corticosterone levels. Finally, we identify that GFRAL signaling governs an anxiety-like behavior in male mice with muscle mitochondrial dysfunction, with females showing a less robust GFRAL-dependent anxiety-like phenotype. Together, we here provide novel evidence of a mitochondrial stress-induced muscle\u2013brain crosstalk via the GDF15-GFRAL axis to modulate food intake and anxiogenic behavior.<\/jats:p>","DOI":"10.26508\/lsa.202201495","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T17:35:15Z","timestamp":1662485715000},"page":"e202201495","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Mitochondrial stress-induced GFRAL signaling controls diurnal food intake and anxiety-like behavior"],"prefix":"10.26508","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3349-5420","authenticated-orcid":true,"given":"Carla","family":"Igual Gil","sequence":"first","affiliation":[{"name":"Department of Physiology of Energy Metabolism, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany"},{"name":"Institute of Nutritional Science, University of Potsdam, Potsdam, 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