短時間断食で脳内ホルモン「コルチコステロン」が分泌され、オートファジーが促進される The brain releases the hormone corticosterone after short fasting that boosts autophagy
2023-04-18 マックス・プランク研究所
これにより、身体の細胞内の不要なものが取り除かれ、エネルギーが生成される。これは、身体を健康で若々しく保つための重要なプロセスであるため、断食が身体にとって健康的である理由を理解する上で役立つ可能性がある。
研究者たちは、これらの発見が長期的に断食の健康的な効果を説明する手助けとなることを期待している。
<関連情報>
- https://www.mpg.de/20182361/0418-neur-hungry-brain-tells-liver-to-start-recycling-153735-x
- https://www.sciencedirect.com/science/article/pii/S1550413123001249?via%3Dihub
栄養を感知するAgRPニューロンが、エネルギー不足時の肝臓オートファジーの制御を中継する Nutrient-sensing AgRP neurons relay control of liver autophagy during energy deprivation
Weiyi Chen, Oliver Mehlkop, Alexandra Scharn, Hendrik Nolte, Paul Klemm, Sinika Henschke, Lukas Steuernagel, Tamara Sotelo-Hitschfeld, Ecem Kaya, Claudia Maria Wunderlich, Thomas Langer, Natalia L. Kononenko, Patrick Giavalisco, Jens Claus Brüning
Cell Metabolism Published: April 18, 2023
DOI:https://doi.org/10.1016/j.cmet.2023.03.019
Highlights
•AgRP-mediated activation of hepatic autophagy flux requires NPY expression
•AgRP → PVH neurocircuitry regulates HPA axis and systemic corticosterone levels
•Inhibition of AgRP activity during a short-term fast blunts hepatic autophagy flux
•Aging impairs fasting-induced HPA axis activation and liver autophagosome formation
Summary
Autophagy represents a key regulator of aging and metabolism in sensing energy deprivation. We find that fasting in mice activates autophagy in the liver paralleled by activation of hypothalamic AgRP neurons. Optogenetic and chemogenetic activation of AgRP neurons induces autophagy, alters phosphorylation of autophagy regulators, and promotes ketogenesis. AgRP neuron-dependent induction of liver autophagy relies on NPY release in the paraventricular nucleus of the hypothalamus (PVH) via presynaptic inhibition of NPY1R-expressing neurons to activate PVHCRH neurons. Conversely, inhibiting AgRP neurons during energy deprivation abrogates induction of hepatic autophagy and rewiring of metabolism. AgRP neuron activation increases circulating corticosterone concentrations, and reduction of hepatic glucocorticoid receptor expression attenuates AgRP neuron-dependent activation of hepatic autophagy. Collectively, our study reveals a fundamental regulatory principle of liver autophagy in control of metabolic adaptation during nutrient deprivation.
