肥満におけるアストロサイトの予期せぬ役割(Obesity: the unexpected role of astrocytes)

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2025-07-07 フランス国立科学研究センター(CNRS)

肥満におけるアストロサイトの予期せぬ役割(Obesity: the unexpected role of astrocytes)
Cross-section of mouse brain showing astrocytes (in green) in the striatum
Rich diet and obesity change the shape of astrocytes, causing them to become reactive, a sign of cerebral inflammation.© Montalban et al / Nature Communication

CNRSとパリ市立大学の研究により、高脂肪食や肥満が線条体にあるアストロサイトの構造と機能を変化させることが明らかになった。マウスの実験では、アストロサイトを化学遺伝学的に操作することで、肥満に伴う代謝異常や認知機能の低下(例:再学習能力)を改善できた。これはアストロサイトが認知機能とエネルギー代謝の両方に重要な役割を果たす初の実証であり、肥満治療の新たな標的となる可能性を示している。

<関連情報>

線条体アストロサイトがマウスの行動柔軟性と全身代謝を調節する Striatal astrocytes modulate behavioral flexibility and whole-body metabolism in mice

Enrica Montalban,Anthony Ansoult,Daniela Herrera Moro Chao,Cuong Pham,Clara Franco,Andrea Contini,Julien Castel,Rim Hassouna,Marene H. Hardonk,Anna Petitbon,Ewout Foppen,Giuseppe Gangarossa,Pierre Trifilieff,Dongdong Li,Serge Luquet & Claire Martin
Nature Communications  Published:07 July 2025
DOI:https://doi.org/10.1038/s41467-025-60968-y

Abstract

Brain circuits in reward-associated behaviors are potent drivers of feeding behavior but also recently emerged as regulator of metabolism. Short or chronic exposures to caloric food alter brain structures and are associated with increased astrocytes reactivity and pro-inflammatory responses in both mice and humans. However, the role of striatal astrocytes in regulating adaptive and maladaptive behavioral and metabolic responses to energy-dense food remains elusive. In this study we reveal that chemogenetic manipulation of the astrocytes in striatal structures can exert a direct effect on peripheral metabolism in male mice, and that manipulation of astrocytes in the dorsal striatum can alter peripheral metabolism and is sufficient to restore cognitive deficit induced by chronic high fat high sucrose (HFHS) diet exposure in obese mice. Altogether, this work reveals a yet unappreciated role for striatal astrocytes as a direct operator of flexible behavior and metabolic control.

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