Linghui Pan, Ruihua Li, Qiqi Li, Qin Zhu, Qian Zhou, Aru Su, Renli Qi, Zuohua Liu, Ruifan Wu, Songbo Wang, Lina Wang, Gang Shu, Qingyan Jiang, Canjun Zhu
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The gut-brain axis mechanism of normal appetite induced by kynurenic acid.
Feeding is essential for both host-organism survival and gut-microbiota maintenance. Our research focuses on how kynurenic acid (KYNA), a gut-microbiota metabolite, regulates appetite during fasting. We find that fasting significantly raises KYNA levels in the intestine, which increases short-term food intake by inhibiting vagal afferent nerve in the nodose ganglion (NG) and activating AgRP neurons in arcuate nucleus (ARCAgRP). The orexigenic effects of KYNA are abolished by subdiaphragmatic vagotomy (sdVx), chemogenetic activation/inhibition of glutamatergic NG/ARCAgRP neurons, inhibiting the nucleus of the solitary tract (NTS) to ARCAgRP inputs, or knockdown of GPR35 (a KYNA receptor) in the intestinal vagal afferent nerve. Our data support a model in which KYNA acts through the GPR35 receptor to inhibit vagal afferent signaling and subsequently activate ARCAgRP neurons, which leads to increased food intake. These findings reveal a mechanism by which gut microbiota controls appetite during fasting, highlighting the complex relationship between microbial and host feeding behavior.
期刊介绍:
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