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Satiety induced by bile acids is mediated via vagal afferent pathways
Xiaoyin Wu, … , Shi-Yi Zhou, Chung Owyang
Xiaoyin Wu, … , Shi-Yi Zhou, Chung Owyang
Published July 23, 2020
Citation Information: JCI Insight. 2020;5(14):e132400. https://doi.org/10.1172/jci.insight.132400.
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Research Article Gastroenterology

Satiety induced by bile acids is mediated via vagal afferent pathways

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Abstract

The aim of this study was to elucidate the role and the pathways used by bile acid receptor TGR5 in transmitting satiety signals. We showed TGR5 colocalized with cholecystokinin type A (CCK-A) receptors in a subpopulation of rat nodose ganglia (NG) neurons. Intra-arterial injection of deoxycholic acid (DCA) dose-dependently increased firing rate in NG while a subthreshold dose of DCA and CCK-8 increased firing rates synergistically. TGR5-specific agonist oleanolic acid induced NG neuronal firing in a dose-dependent manner. However, the same units did not respond to GW4064, a nuclear receptor–specific agonist. Quantity of DCA-activated neurons in the hypothalamus was determined by c-Fos expression. Combining DCA and CCK-8 caused a 4-fold increase in c-Fos activation. In the arcuate nucleus, c-Fos–positive neurons coexpressed cocaine and amphetamine regulated transcript and proopiomelanocortin. DCA-induced c-Fos expression was eliminated following truncal vagotomy or silencing of TGR5 in the NG. Feeding studies showed intravenous injection of 1 μg/kg of DCA reduced food intake by 12% ± 3%, 24% ± 5%, and 32% ± 6% in the first 3 hours, respectively. Silencing of TGR5 or CCK-A receptor in the NG enhanced spontaneous feeding by 18% ± 2% and 13.5% ± 2.4%, respectively. When both TGR5 and CCK-A receptor were silenced, spontaneous feeding was enhanced by 37% ± 4% in the first 3 hours, suggesting that bile acid may have a physiological role in regulating satiety. Working in concert with CCK, bile acid synergistically enhanced satiety signals to reduce spontaneous feeding.

Authors

Xiaoyin Wu, Ji-Yao Li, Allen Lee, Yuan-Xu Lu, Shi-Yi Zhou, Chung Owyang

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Figure 3

TGR5 is responsible for bile acid–induced vagal afferent neuron firing.

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TGR5 is responsible for bile acid–induced vagal afferent neuron firing.
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(A) A representative recording demonstrates response of vagal afferent neurons to oleanolic acid (OA), a TGR5 agonist, but not to the nuclear receptor agonist GW4064 (top panel), given via the superior mesenteric artery. Vagal afferent neurons responded to the administration of OA following infusion of GW4064 (bottom panel). Thirty-six units from 6 rats were recorded. (B) Silencing of TGR5 in NG abolished the effect of DCA on neuron firing; however, the same unit responded to CCK-8. Twenty-four units from 6 rats were recorded. (C) Summarized data showing administration of OA resulted in a dose-dependent increase in firing rates per 10 seconds. This effect was not seen with GW4064. Silencing of TGR5 abolished the effect of DCA on neuron firing, but the same units responded to CCK-8. All the doses of drugs are expressed as micrograms per kilogram. *P < 0.05, **P < 0.01 compared with basal firing, n = 6. One-way ANOVA with Tukey’s test.

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