期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/ijms23094679
关键词
orexin; IGF-I; central control of metabolism; circadian activity; feeding entrainment
资金
- Ciberned (Instituto de Salud Carlos III, Spain)
- Inter-CIBER project [PIE14/00061]
- MCIN/AEI [PID2019-104376RB-I00]
- Comunidad de Madrid through the European Social Fund (ESF) [B2017/BMD-3700]
- Fulbright grant
The uncoupling of metabolism and circadian activity increases the risk of various pathologies. Insulin and IGF-I have been found to regulate feeding patterns and circadian rhythms. IGF-I modulates orexin neurons to align metabolism and circadian rhythms, which is essential in preventing metabolic disorders and diseases.
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 activity patterns which preceded the appearance of metabolic disturbances. Thus, Firoc males developed hyperglycemia and glucose intolerance, while females developed obesity. Since IGF-I directly modulates orexin levels and hepatic expression of KLF genes involved in circadian and metabolic entrainment in an orexin-dependent manner, it seems that IGF-I entrains metabolism and circadian rhythms by modulating the activity of orexin neurons.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据