The ability to coordinate behavioral responses with metabolic status is fundamental to the maintenance of energy homeostasis. In numerous species including Caenorhabditis elegans and mammals, neural serotonin signaling regulates a range of food-related behaviors. However, the mechanisms that integrate metabolic information with serotonergic circuits are poorly characterized. Here, we identify metabolic, molecular, and cellular components of a circuit that links peripheral metabolic state to serotonin-regulated behaviors in C. elegans. We find that blocking the entry of fatty acyl coenzyme As (CoAs) into peroxisomal β-oxidation in the intestine blunts the effects of neural serotonin signaling on feeding and egg-laying behaviors. Comparative genomics and metabolomics revealed that interfering with intestinal peroxisomal β-oxidation results in a modest global transcriptional change but significant changes to the metabolome, including a large number of changes in ascaroside and phospholipid species, some of which affect feeding behavior. We also identify body cavity neurons and an ether-a-go-go (EAG)-related potassium channel that functions in these neurons as key cellular components of the circuitry linking peripheral metabolic signals to regulation of neural serotonin signaling. These data raise the possibility that the effects of serotonin on satiety may have their origins in feedback, homeostatic metabolic responses from the periphery.

中文翻译：

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肠道过氧化物酶体脂肪酸β-氧化通过反馈机制调节神经元5-羟色胺信号传导。

协调行为反应与代谢状态的能力是维持能量稳态的基础。在包括秀丽隐杆线虫（Caenorhabditis elegans）和哺乳动物在内的许多物种中，神经元5-羟色胺信号传导调节一系列与食物相关的行为。但是，整合代谢信息与5-羟色胺能回路的机制的特征较差。在这里，我们确定电路的代谢，分子和细胞成分，这些成分将周围的代谢状态与秀丽隐杆线虫中5-羟色胺调节的行为联系起来。我们发现阻止脂肪酰基辅酶As（CoAs）进入肠道的过氧化物酶体β-氧化会钝化神经素5-羟色胺信号传导对进食和产卵行为的影响。比较基因组学和代谢组学研究表明，干扰肠道过氧化物酶体β-氧化导致适度的整体转录变化，但代谢组发生重大变化，其中包括scar螨甙和磷脂种类的大量变化，其中一些影响摄食行为。我们还确定了体腔神经元和一个以太（EAG）相关的钾通道，这些钾通道在这些神经元中起着关键的细胞成分的作用，该电路将周围的代谢信号连接到神经5-羟色胺信号传导的调节上。这些数据增加了5-羟色胺对饱腹感的影响可能起源于周围环境的反馈，稳态代谢反应。包括a螨和磷脂种类的大量变化，其中一些影响进食行为。我们还确定了体腔神经元和一个以太（EAG）相关的钾通道，这些钾通道在这些神经元中起着关键的细胞成分的作用，该电路将周围的代谢信号连接到神经5-羟色胺信号传导的调节上。这些数据增加了5-羟色胺对饱腹感的影响可能起源于周围环境的反馈，稳态代谢反应。包括a螨和磷脂种类的大量变化，其中一些影响进食行为。我们还确定了体腔神经元和一个以太（EAG）相关的钾通道，这些钾通道在这些神经元中起着关键的细胞成分的作用，该电路将周围的代谢信号连接到神经5-羟色胺信号传导的调节上。这些数据增加了5-羟色胺对饱腹感的影响可能起源于周围环境的反馈，稳态代谢反应。