Central FGF21 production regulates memory but not peripheral metabolism

Bolu Zhou; Kristin E. Claflin; Kyle H. Flippo; Andrew I. Sullivan; Arvand Asghari; Satya M. Tadinada; Sharon O. Jensen-Cody; Ted Abel; Matthew J. Potthoff

doi:10.1016/j.celrep.2022.111239

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Central FGF21 production regulates memory but not peripheral metabolism

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Central FGF21 production regulates memory but not peripheral metabolism

Bolu Zhou, Kristin E. Claflin, Kyle H. Flippo, Andrew I. Sullivan, Arvand Asghari, Satya M. Tadinada, Sharon O. Jensen-Cody, Ted Abel and Matthew J. Potthoff

Cell reports (Cambridge), Vol.40(8), 111239

08/23/2022

DOI: 10.1016/j.celrep.2022.111239

PMCID: PMC9472585

PMID: 36001982

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Abstract

Fibroblast growth factor 21 (FGF21) is a liver-derived endocrine hormone that functions to regulate energy homeostasis and macronutrient intake. Recently, FGF21 was reported to be produced and secreted from hypothalamic tanycytes, to regulate peripheral lipid metabolism; however, rigorous investigation of FGF21 expression in the brain has yet to be accomplished. Using a mouse model that drives CRE recombinase in FGF21-expressing cells, we demonstrate that FGF21 is not expressed in the hypothalamus, but instead is produced from the retrosplenial cortex (RSC), an essential brain region for spatial learning and memory. Furthermore, we find that central FGF21 produced in the RSC enhances spatial memory but does not regulate energy homeostasis or sugar intake. Finally, our data demonstrate that administration of FGF21 prolongs the duration of long-term potentiation in the hippocampus and enhances activation of hippocampal neurons. Thus, endogenous and pharmacological FGF21 appear to function in the hippocampus to enhance spatial memory. [Display omitted] •FGF21 is not produced from hypothalamic tanycytes•Instead, FGF21 is expressed in the brain in the retrosplenial cortex•Brain-derived FGF21 regulates memory formation but not metabolism•FGF21 signaling to the hippocampus prolongs the duration of long-term potentiation Zhou et al. reveal that the endocrine hormone FGF21 is expressed in the brain. Central FGF21 expression occurs in distinct areas, including the retrosplenial cortex, but not the hypothalamus. Interestingly, brain-derived FGF21 regulates spatial memory formation, but not metabolism, and the converse is true for liver-derived FGF21.

betaklotho

central

FGF21

hippocampus

hypothalamus

liver

memory

tanycytes

Details

Title: Subtitle: Central FGF21 production regulates memory but not peripheral metabolism
Creators: Bolu Zhou - University of Iowa
Kristin E. Claflin - University of Iowa
Kyle H. Flippo - University of Iowa
Andrew I. Sullivan - University of Iowa
Arvand Asghari - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, 169 Newton Road, 3322 PBDB, Iowa City, IA 52242, USA
Satya M. Tadinada - University of Iowa
Sharon O. Jensen-Cody - University of Iowa
Ted Abel - University of Iowa
Matthew J. Potthoff - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, 169 Newton Road, 3322 PBDB, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Cell reports (Cambridge), Vol.40(8), 111239
DOI: 10.1016/j.celrep.2022.111239
PMID: 36001982
PMCID: PMC9472585
NLM abbreviation: Cell Rep
ISSN: 2211-1247
eISSN: 2211-1247
Publisher: Elsevier Inc
Language: English
Date published: 08/23/2022
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984286160202771

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