Intestine-brain axis mechanism of 3-indolepropionic acid regulating animal feeding through vagus nerve

<bold>Objective</bold> Appetite is the most important factor affecting feed intake，multiple signals from central and peripheral sources can regulate feeding via the hypothalamic appetite center，and the intestine-brain axis plays an important role in appetite regulation in animals.This study aims to reveal the mechanism of intestine-brain axis in mediating 3-indolepropionic acid in regulating feed intake of animals，which is of high reference value for improving feed intake of animals. <bold>Method</bold> Twenty one 8-week-old C57BL/6J male mice were used as test subjects.The effects of different concentrations of 3-indolepropionic acid and normal saline on feed intake and body weight gain of mice were detected and analyzed respectively.Subsequently，techniques such as subdiaphragmatic vagotomy，c-Fos immunofluorescence and pharmacogenetics were used to reveal the neural circuitry of 3-indolepropionic acid in regulating the excitability of neurons in the nucleus tractus solitarius via the vagus nerve. <bold>Result</bold> （1）Compared with the control group，10 mg/kg of 3-indolepropionic acid significantly increased the feed intake of mice for 3 h（<italic>P</italic>&lt;0.05）；3-indolepropionic acid increased the feed intake of mice through the activation of solitary tract nucleus（SCTN）neurons（<italic>P</italic>&lt;0.01），and chemogenetic inhibition of the SCTN neurons eliminated the feeding-promoting effect of 3-indolepropionic acid；（2）3-Indolepropionic acid activated NG neurons through intestinal vagus nerve（<italic>P</italic>&lt;0.001）.Subphrenic vagotomy or chemical genetic activation of NG ganglion could eliminate the effect of 3-Indolepropionic acid on food intake. <bold>Conclusion</bold> 3-indolepropionic acid activates solitary tract nucleus neurons through intestinal vagal neurotransmission，thereby increasing food intake in animals.