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ID 117270
著者
志内, 哲也 Tokushima University|Japan Science and Technology Agency 徳島大学 教育研究者総覧 KAKEN研究者をさがす
Otsuka, Airi Tokushima University
Séi, Hiroyoshi Tokushima University
キーワード
AgRP
glucocorticoid
feeding rhythm
insulin sensitivity
skeletal muscle
資料タイプ
学術雑誌論文
抄録
Circadian phase shifts in peripheral clocks induced by changes in feeding rhythm often result in insulin resistance. However, whether the hypothalamic control system for energy metabolism is involved in the feeding rhythm-related development of insulin resistance is unknown. Here, we show the physiological significance and mechanism of the involvement of the agouti-related protein (AgRP) in evening feeding-associated alterations in insulin sensitivity. Evening feeding during the active dark period increased hypothalamic AgRP expression and skeletal muscle insulin resistance in mice. Inhibiting AgRP expression by administering an antisense oligo or a glucocorticoid receptor antagonist mitigated these effects. AgRP-producing neuron-specific glucocorticoid receptor-knockout (AgRP-GR-KO) mice had normal skeletal muscle insulin sensitivity even under evening feeding schedules. Hepatic vagotomy enhanced AgRP expression in the hypothalamus even during ad-lib feeding in wild-type mice but not in AgRP-GR-KO mice. The findings of this study indicate that feeding in the late active period may affect hypothalamic AgRP expression via glucocorticoids and induce skeletal muscle insulin resistance.
掲載誌名
International Journal of Molecular Sciences
ISSN
14220067
出版者
MDPI
22
19
開始ページ
10831
発行日
2021-10-07
権利情報
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
医学系