biostudies-literaturePignatelli JBiomedical Research Networking Center on Neurodegenerative DiseasesComunidad de MadridMinisterio de ciencia e innovación. Agencia estatal de investigación4679https://www.ebi.ac.uk/biostudies/studies/S-EPMC9101627biostudies-literatureUnknown23(9)Uncoupling of metabolism and circadian activity is associated with an increased risk of a wide spectrum of pathologies. Recently, insulin and the closely related insulin-like growth factor I (IGF-I) were shown to entrain feeding patterns with circadian rhythms. Both hormones act centrally to modulate peripheral glucose metabolism; however, whereas central targets of insulin actions are intensely scrutinized, those mediating the actions of IGF-I remain less defined. We recently showed that IGF-I targets orexin neurons in the lateral hypothalamus, and now we evaluated whether IGF-I modulates orexin neurons to align circadian rhythms with metabolism. Mice with disrupted IGF-IR activity in orexin neurons (Firoc mice) showed sexually dimorphic alterations in daily glucose rhythms and feeding acInternational journal of molecular sciencesInsulin-like Growth Factor I Couples Metabolism with Circadian Activity through Hypothalamic Orexin Neurons.PMC9101627B2017/BMD-3700PID2019-104376RB-I00PIE14/00061Horrillo DAleman ITPignatelli Jde Sevilla MEFSperber JMedina-Gomez GfalseInsulin-like Growth Factor I Couples Metabolism with Circadian Activity through Hypothalamic Orexin Neurons.Uncoupling of metabolism and circadian activity is associated with an increased risk of a wide spectrum of pathologies. Recently, insulin and the closely related insulin-like growth factor I (IGF-I) were shown to entrain feeding patterns with circadian rhythms. Both hormones act centrally to modulate peripheral glucose metabolism; however, whereas central targets of insulin actions are intensely scrutinized, those mediating the actions of IGF-I remain less defined. We recently showed that IGF-I targets orexin neurons in the lateral hypothalamus, and now we evaluated whether IGF-I modulates orexin neurons to align circadian rhythms with metabolism. Mice with disrupted IGF-IR activity in orexin neurons (Firoc mice) showed sexually dimorphic alterations in daily glucose rhythms and feeding ac2022-01-01T00:00:00Z2022 Apr2025-04-04T22:53:04.777Z2025-02-19T00:55:41.143ZS-EPMC91016273556306910.3390/ijms23094679