Negative feedback regulation of alcohol ingestion through the FGF21-PVH oxytocin-VTA dopamine system
Abstract
Alcohol has a notable negative impact on global health. Understanding its physiological regulation is crucial to addressing alcohol use. Here, we show that FGF21-oxytocin neurons in the paraventricular nucleus of the hypothalamus (PVH OXT )-dopamine neurons in the ventral tegmental area (VTA DA ) negatively regulate the drive to drink alcohol. Alcohol induces FGF21 signaling, which activates PVH OXT and induces oxytocin release in the VTA. The VTA DA neurons are activated hours after alcohol ingestion, which reduces the drive to drink alcohol, extends the interdrink interval, and thereby reduces alcohol consumption. The system is downregulated in a mouse model of alcohol dependence, and activating the system with FGF21-inducing sugars reduces alcohol ingestion and prevents binge drinking and alcohol dependence. Therefore, FGF21-inducing nutraceuticals can substitute for alcohol by supplementing the FGF21-PVH OXT -VTA DA negative feedback signal to attenuate alcohol-related behaviors in mice.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (13)
Sho Matsui
Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University
Yuma Takahashi
Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University
Shuhei Morioka
Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University
Takaaki Ozawa
Laboratory for Advanced Brain Functions, Institute for Protein Research, Osaka University
Sachiho Kanayama
Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University
Hiroki Iwama
Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University
Lan Geng
State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University
Kazuhiro Umemoto
Laboratory for Advanced Brain Functions, Institute for Protein Research, Osaka University
Yasuo Oguri
Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University
Satoshi Tsuzuki
Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University
Yulong Li
Takatoshi Hikida
Laboratory for Advanced Brain Functions, Institute for Protein Research, Osaka University
Tsutomu Sasaki
Metabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma University