FGF21 suppresses alcohol consumption through an amygdalo-striatal circuit

流式;FACS;单细胞测序;single cell sequencing; FGF21; alcohol; 酒精;basolateral amygdala;基底外侧杏仁核;betaklotho; βklotho;brain;大脑；hepatokine; liver; 肝脏;nucleus accumbens

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期刊 Cell Metab
时间 2022
影响因子 30.9
起止号 34(2):317-328.e6
种属 Mouse
技术平台单细胞测序
应用领域神经系统
样本类型 brain tissue
研究方向神经系统
doi 10.1016/j.cmet.2021.12.024.

Abstract

Excessive alcohol consumption is a major health and social issue in our society. Pharmacologic administration of the endocrine hormone fibroblast growth factor 21 (FGF21) suppresses alcohol consumption through actions in the brain in rodents, and genome-wide association studies have identified single nucleotide polymorphisms in genes involved with FGF21 signaling as being associated with increased alcohol consumption in humans. However, the neural circuit(s) through which FGF21 signals to suppress alcohol consumption are unknown, as are its effects on alcohol consumption in higher organisms. Here, we demonstrate that administration of an FGF21 analog to alcohol-preferring non-human primates reduces alcohol intake by 50%. Further, we reveal that FGF21 suppresses alcohol consumption through a projection-specific subpopulation of KLB-expressing neurons in the basolateral amygdala. Our results illustrate how FGF21 suppresses alcohol consumption through a specific population of neurons in the brain and demonstrate its therapeutic potential in non-human primate models of excessive alcohol consumption.

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Abstract