Scholarlink

<p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

High-fat diet disrupts a septal control on feeding to promote obesity in male mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月27日

查看全文
  • Shaolei Jiang,
  • Shishi Lai,
  • Haiyang Jing,
  • Xiaocong Wu,
  • Fengling Li,
  • Bo Chen,
  • Jin Bao,
  • Liping Wang,
  • Gaowei Chen,
  • Yingjie Zhu

摘要

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.