Feeding Rhythm-Induced Hypothalamic Agouti-Related Protein Elevation via Glucocorticoids Leads to Insulin Resistance in Skeletal Muscle
| Autor: | Sachiko Chikahisa, Tetsuya Shiuchi, Hiroyoshi Sei, Airi Otsuka, Noriyuki Shimizu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
feeding rhythm Mice chemistry.chemical_compound Agouti-Related Protein Biology (General) Spectroscopy Antiglucocorticoid digestive oral and skin physiology General Medicine Computer Science Applications Peripheral Chemistry medicine.anatomical_structure Hypothalamus Glucocorticoid hormones hormone substitutes and hormone antagonists medicine.drug medicine.medical_specialty Evening QH301-705.5 Period (gene) Biology Article Catalysis Inorganic Chemistry Receptors Glucocorticoid Insulin resistance Internal medicine medicine Animals insulin sensitivity Physical and Theoretical Chemistry skeletal muscle Muscle Skeletal Glucocorticoids Molecular Biology QD1-999 Organic Chemistry Skeletal muscle Feeding Behavior medicine.disease Mice Inbred C57BL Endocrinology chemistry nervous system glucocorticoid Insulin Resistance Energy Metabolism AgRP |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 10831, p 10831 (2021) International Journal of Molecular Sciences Volume 22 Issue 19 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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