2026-01-05 中国科学院(CAS)
<関連情報>
- https://english.cas.cn/newsroom/research_news/life/202601/t20260105_1145175.shtml
- https://www.nature.com/articles/s41467-025-68010-x
高脂肪食は雄マウスの摂食に対する中隔制御を破壊し、肥満を促進する High-fat diet disrupts a septal control on feeding to promote obesity in male mice
Shaolei Jiang,Shishi Lai,Haiyang Jing,Xiaocong Wu,Fengling Li,Bo Chen,Jin Bao,Liping Wang,Gaowei Chen & Yingjie Zhu
Nature Communications Published:27 December 2025
DOI:https://doi.org/10.1038/s41467-025-68010-x An unedited version of this manuscript.
Abstract
The global epidemic of diet-induced obesity poses a significant health challenge. Among brain regions regulating energy homeostasis, the lateral septum has emerged as a critical brake on feeding behavior to prevent overeating. However, the neural adaptations within the septal area under high-fat diet (HFD) and consequent contributions to obesity remain unknown. Utilizing high-throughput single-nucleus RNA sequencing, slice electrophysiology and in vivo calcium imaging, we identified HFD-induced alterations in the transcriptional profiles and neural activity within the septal area of male mice. The HFD suppresses septal neuronal activity by downregulating hyperpolarization-activated cyclic nucleotide-gated channel 1 (Hcn1), and weakens inhibitory control over downstream targets through reduced expression of glutamate decarboxylase 2 (Gad2). Overexpression of Hcn1 and Gad2 enhances septal neuronal activity, restores GABA levels, and prevents HFD-driven overeating and obesity. These findings illustrate how diet disrupts the brain’s feeding suppression system, leading to overeating and obesity.
