Scholarlink

<p>Feeding is tightly regulated by hypothalamic circuits that integrate circadian and metabolic cues, yet the neuromodulatory systems coordinating these signals remain incompletely understood. Cholinergic neurons within the arcuate nucleus (ARC) constitute an incompletely characterized population whose role in energy balance and feeding rhythms has not been fully defined. Here, we investigated whether chemogenetic activation of ARC cholinergic neurons modulates food intake in a circadian- and diet-dependent manner. Using Chat-Cre transgenic mice expressing hM3D(Gq) receptors in ARC cholinergic neurons, we assessed food intake following systemic clozapine administration during the light (diurnal/inactive) and dark (nocturnal/active) phases under both standard chow and high-fat diet conditions. Activation of ARC cholinergic neurons significantly increased chow consumption during the dark phase but not during the light phase, demonstrating a circadian-gated orexigenic effect accompanied by compensatory reductions in light-phase intake, resulting in unchanged total daily consumption. In contrast, the same stimulation failed to alter feeding under high-fat diet exposure, suggesting that hedonic mechanisms may mask cholinergic modulation within hypothalamic circuits. These findings identify ARC cholinergic neurons as a state-dependent neuromodulatory population that promotes feeding selectively during the active phase and under metabolic, but not hedonic, conditions, revealing a novel dimension of hypothalamic cholinergic signaling relevant to metabolic regulation.</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

Circadian phase and diet shape feeding responses to arcuate cholinergic neuron activation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月29日

查看全文
  • Mustafa Can Kiren,
  • Gülsena Baydaş,
  • Büşra Züleyha Doğan,
  • Mustafa Hilmi Pekalp,
  • Muhammed İkbal Alp,
  • Ertuğrul Kılıç

摘要

Feeding is tightly regulated by hypothalamic circuits that integrate circadian and metabolic cues, yet the neuromodulatory systems coordinating these signals remain incompletely understood. Cholinergic neurons within the arcuate nucleus (ARC) constitute an incompletely characterized population whose role in energy balance and feeding rhythms has not been fully defined. Here, we investigated whether chemogenetic activation of ARC cholinergic neurons modulates food intake in a circadian- and diet-dependent manner. Using Chat-Cre transgenic mice expressing hM3D(Gq) receptors in ARC cholinergic neurons, we assessed food intake following systemic clozapine administration during the light (diurnal/inactive) and dark (nocturnal/active) phases under both standard chow and high-fat diet conditions. Activation of ARC cholinergic neurons significantly increased chow consumption during the dark phase but not during the light phase, demonstrating a circadian-gated orexigenic effect accompanied by compensatory reductions in light-phase intake, resulting in unchanged total daily consumption. In contrast, the same stimulation failed to alter feeding under high-fat diet exposure, suggesting that hedonic mechanisms may mask cholinergic modulation within hypothalamic circuits. These findings identify ARC cholinergic neurons as a state-dependent neuromodulatory population that promotes feeding selectively during the active phase and under metabolic, but not hedonic, conditions, revealing a novel dimension of hypothalamic cholinergic signaling relevant to metabolic regulation.