FGF21 suppresses alcohol consumption through an amygdalo-striatal circuit

Kyle H Flippo, Samuel A J Trammell, Matthew P Gillum, Iltan Aklan, Misty B Perez, Yavuz Yavuz, Nicholas K Smith, Sharon O Jensen-Cody, Bolu Zhou, Kristin E Claflin, Amy Beierschmitt, Anders Fink-Jensen, Filip K Knop, Roberta M Palmour, Brad A Grueter, Deniz Atasoy, Matthew J Potthoff

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.

Original languageEnglish
JournalCell Metabolism
Volume34
Issue number2
Pages (from-to)317-328.e6
ISSN1550-4131
DOIs
Publication statusPublished - 1 Feb 2022

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