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González-Vila, A.* ; Luengo-Mateos, M.* ; Silveira-Loureiro, M.* ; Garrido-Gil, P.* ; Ohinska, N.* ; González-Domínguez, M.* ; Labandeira-García, J.L.* ; García-Cáceres, C. ; López, M.* ; Barca-Mayo, O.*

Astrocytic insulin receptor controls circadian behavior via dopamine signaling in a sexually dimorphic manner.

Nat. Commun. 14:8175 (2023)

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Mammalian circadian clocks respond to feeding and light cues, adjusting internal rhythms with day/night cycles. Astrocytes serve as circadian timekeepers, driving daily physiological rhythms; however, it's unknown how they ensure precise cycle-to-cycle rhythmicity. This is critical for understanding why mistimed or erratic feeding, as in shift work, disrupts circadian physiology- a condition linked to type 2 diabetes and obesity. Here, we show that astrocytic insulin signaling sets the free-running period of locomotor activity in female mice and food entrainment in male mice. Additionally, ablating the insulin receptor in hypothalamic astrocytes alters cyclic energy homeostasis differently in male and female mice. Remarkably, the mutants exhibit altered dopamine metabolism, and the pharmacological modulation of dopaminergic signaling partially restores distinct circadian traits in both male and female mutant mice. Our findings highlight the role of astrocytic insulin-dopaminergic signaling in conveying time-of-feeding or lighting cues to the astrocyte clock, thus governing circadian behavior in a sex-specific manner.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Cerebral Glucose-utilization; Food-anticipatory Activity; Suprachiasmatic Nucleus; Gene-expression; Locomotor-activity; Arcuate Nucleus; Sex-differences; Clock; Entrainment; Metabolism

ISSN (print) / ISBN 2041-1723

e-ISSN 2041-1723

Journal Nature Communications

Quellenangaben Volume: 14, Issue: 1, Article Number: 8175

Publisher Nature Publishing Group

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Obesity (IDO)

Grants Ministerio de Ciencia e Innovacin - FEDER Program of EU
German Research Foundation DFG under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology
Ministerio de Ciencia, Innovacin y Universidades of Spain
Xunta de Galicia, Conselleria de Cultura, Educacion e Ordenacion Universitaria
Agencia Estatal de Investigacion
Ministry of Economy and Competitiveness | Agencia Estatal de Investigacin (Spanish Agencia Estatal de Investigacin)
Ministerio de Ciencia, e Innovacion of Spain
European Research Council ERC
German Research Foundation DFG under Germany's Excellence Strategy
Helmholtz Association-Initiative and Networking Fund
Xunta de Galicia
Ministerio de Ciencia, Innovacion y Universidades of Spain
Ministerio de Ciencia e Innovacion - FEDER Program of EU