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

doi:10.1016/j.cmet.2021.12.024

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FGF21 suppresses alcohol consumption through an amygdalo-striatal circuit

Journal article

Open access

Peer reviewed

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, …

Cell metabolism, Vol.34(2), pp.317-328.e6

02/01/2022

DOI: 10.1016/j.cmet.2021.12.024

PMCID: PMC9093612

PMID: 35108517

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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.

alcohol

betaklotho

liver

hepatokine

basolateral amygdala

nucleus accumbens

brain

FGF21

Details

Title: Subtitle: FGF21 suppresses alcohol consumption through an amygdalo-striatal circuit
Creators: Kyle H Flippo - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA. Electronic address: kyle-flippo@uiowa.edu
Samuel A J Trammell - Section for Nutrient and Metabolite Sensing, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen, Denmark
Matthew P Gillum - Section for Nutrient and Metabolite Sensing, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen, Denmark
Iltan Aklan - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Misty B Perez - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Yavuz Yavuz - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Nicholas K Smith - Department of Anesthesiology, Vanderbilt University, Nashville, TN 37323, USA
Sharon O Jensen-Cody - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Bolu Zhou - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Kristin E Claflin - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Amy Beierschmitt - School of Veterinary Medicine, Ross University, Basseterre KN 0101, Saint Kitts and Nevis; Behavioral Science Foundation, Basseterre KN 0101, Saint Kitts and Nevis
Anders Fink-Jensen - Laboratory of Neuropsychiatry, Psychiatric Centre Copenhagen and University Hospital of Copenhagen, Edel Sauntes Allé 10, DK-2100 Copenhagen, Denmark
Filip K Knop - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Gentofte Hospitalsvej 7, 3rd floor, DK-2900 Hellerup, Denmark; Steno Diabetes Center Copenhagen, 2820 Gentofte, Denmark
Roberta M Palmour - Behavioral Science Foundation, Basseterre KN 0101, Saint Kitts and Nevis; Departments of Psychiatry and Human Genetics, McGill University, Montreal, QC, Canada
Brad A Grueter - Department of Anesthesiology, Vanderbilt University, Nashville, TN 37323, USA
Deniz Atasoy - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Matthew J Potthoff - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Department of Veterans Affairs Medical Center, Iowa City, IA 52242, USA. Electronic address: matthew-potthoff@uiowa.edu
Resource Type: Journal article
Publication Details: Cell metabolism, Vol.34(2), pp.317-328.e6
DOI: 10.1016/j.cmet.2021.12.024
PMID: 35108517
PMCID: PMC9093612
NLM abbreviation: Cell Metab
ISSN: 1550-4131
eISSN: 1932-7420
Grant note: R01 DK106104 / NIDDK NIH HHS F31 DK117515 / NIDDK NIH HHS F32 DK117510 / NIDDK NIH HHS R01 DK126740 / NIDDK NIH HHS R01 AA027654 / NIAAA NIH HHS T32 DK112751 / NIDDK NIH HHS
Language: English
Date published: 02/01/2022
Academic Unit: Neurology; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
Record Identifier: 9984215127902771

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