徳島大学 教育・研究者情報データベース(EDB)

1. 志内 哲也

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2. (英) Otsuka Airi

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3. 清水 紀之

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4. (英) Chikahisa Sachiko

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5. 勢井 宏義([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.生理系.生理学])

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(英) Feeding Rhythm-Induced Hypothalamic Agouti-Related Protein Elevation via Glucocorticoids Leads to Insulin Resistance in Skeletal Muscle.

(英) 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.

1. (英) Agouti-Related Protein
2. (英) Animals
3. エネルギー代謝(energy metabolism)
4. (英) Feeding Behavior
5. (英) Glucocorticoids
6. 視床下部(hypothalamus)
7. インスリン抵抗性(insulin resistance)
8. 男性(male)
9. (英) Mice
10. (英) Mice, Inbred C57BL
11. (英) Muscle, Skeletal
12. (英) Receptors, Glucocorticoid

1. (英) PublicationType: Journal Article