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bioRxiv · 10.1101/2021.02.07.429949

Insulin-Like Growth Factor I Couples Metabolism With Circadian Activity Through Hypothalamic Orexin Neurons

Pignatelli, J.·Fernandez de Sevilla, M. E.·Sperber, J.·Horrillo, D.·Medina-Gomez, G.·Torres Aleman, I.
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Abstract

Uncoupling of metabolism and circadian activity is associated with an increased risk of various pathologies, including neurodegeneration. Recently, insulin and the closely related insulin-like growth factor I (IGF-I) were shown to entrain feeding patterns with circadian rhythms. Moreover, 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 undefined. We analyzed whether IGF-I targets orexin neurons in the lateral hypothalamus, as these neurons are involved in circadian rhythms and energy allocation, and are modulated by IGF-I. Mice with disrupted IGF-IR activity in orexin neurons show phase shifts in circadian feeding behavior, loss of circadian orexin expression, and gradually develop sex-dependent metabolic alterations. In addition, modulation by IGF-I of hepatic KLF transcription factors involved in peripheral glucose metabolism is mediated by orexin neurons. Thus, IGF-I entrains energy metabolism and circadian rhythms through hypothalamic orexin neurons.

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Pignatelli, J., Fernandez de Sevilla, M. E., Sperber, J., Horrillo, D., Medina-Gomez, G., Torres Aleman, I.. 2021-02-08. Insulin-Like Growth Factor I Couples Metabolism With Circadian Activity Through Hypothalamic Orexin Neurons. https://doi.org/10.1101/2021.02.07.429949

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