FGF21 promotes thermogenic gene expression as an autocrine factor in adipocytes.

3T3-L1 Cells Adipocytes / metabolism Adipose Tissue, Brown / metabolism Adipose Tissue, White / metabolism Adrenergic beta-Agonists Animals Autocrine Communication / genetics Fibroblast Growth Factors / blood Gene Expression Regulation Lipolysis Liver / metabolism Mice Organ Specificity Protein Binding RNA, Messenger / genetics Receptors, Adrenergic, beta-3 / metabolism Receptors, Fibroblast Growth Factor / metabolism Thermogenesis / genetics
Beiging Browning FGF21 adipose adrenergic autocrine beige thermogenic

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
29 06 2021
Historique:
received: 14 10 2020
revised: 04 03 2021
accepted: 09 06 2021
entrez: 30 6 2021
pubmed: 1 7 2021
medline: 11 2 2022
Statut: ppublish

Résumé

The contribution of adipose-derived FGF21 to energy homeostasis is unclear. Here we show that browning of inguinal white adipose tissue (iWAT) by β-adrenergic agonists requires autocrine FGF21 signaling. Adipose-specific deletion of the FGF21 co-receptor β-Klotho renders mice unresponsive to β-adrenergic stimulation. In contrast, mice with liver-specific ablation of FGF21, which eliminates circulating FGF21, remain sensitive to β-adrenergic browning of iWAT. Concordantly, transgenic overexpression of FGF21 in adipocytes promotes browning in a β-Klotho-dependent manner without increasing circulating FGF21. Mechanistically, we show that β-adrenergic stimulation of thermogenic gene expression requires FGF21 in adipocytes to promote phosphorylation of phospholipase C-γ and mobilization of intracellular calcium. Moreover, we find that the β-adrenergic-dependent increase in circulating FGF21 occurs through an indirect mechanism in which fatty acids released by adipocyte lipolysis subsequently activate hepatic PPARα to increase FGF21 expression. These studies identify FGF21 as a cell-autonomous autocrine regulator of adipose tissue function.

Identifiants

DOI: 10.1016/j.celrep.2021.109331 PMID: 34192547 PMC: PMC8293281
pubmed: 34192547
pii: S2211-1247(21)00707-5
doi: 10.1016/j.celrep.2021.109331
pmc: PMC8293281
mid: NIHMS1720099
pii:
doi:

Substances chimiques

Adrenergic beta-Agonists 0
RNA, Messenger 0
Receptors, Adrenergic, beta-3 0
Receptors, Fibroblast Growth Factor 0
fibroblast growth factor 21 0
Fibroblast Growth Factors 62031-54-3

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

109331

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK125820
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007044
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK124496
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA028473
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK120480
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK105075
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK126944
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK122804
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK073368
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK076906
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIEHS NIH HHS
ID : P42 ES010337
Pays : United States
Organisme : NIDDK NIH HHS
ID : F32 DK124947
Pays : United States
Organisme : NIDDK NIH HHS
ID : R03 DK118195
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK063491
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG051459
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK067158
Pays : United States
Organisme : NIDDK NIH HHS
ID : R37 DK057978
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK117551
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK057978
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014195
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests A.R.S. is a founder of Elgia Therapeutics. The other authors declare no competing interests.

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Auteurs

Mohammad Abu-Odeh (M)

Department of Medicine, University of California, San Diego, San Diego, CA 92093, USA.

Yuan Zhang (Y)

Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA.

Shannon M Reilly (SM)

Department of Medicine, University of California, San Diego, San Diego, CA 92093, USA.

Nima Ebadat (N)

Department of Medicine, University of California, San Diego, San Diego, CA 92093, USA.

Omer Keinan (O)

Department of Medicine, University of California, San Diego, San Diego, CA 92093, USA.

Joseph M Valentine (JM)

Department of Medicine, University of California, San Diego, San Diego, CA 92093, USA.

Maziar Hafezi-Bakhtiari (M)

Department of Medicine, University of California, San Diego, San Diego, CA 92093, USA.

Hadeel Ashayer (H)

Department of Medicine, University of California, San Diego, San Diego, CA 92093, USA.

Lana Mamoun (L)

Department of Medicine, University of California, San Diego, San Diego, CA 92093, USA.

Xin Zhou (X)

Department of Pharmacology, University of California, San Diego, San Diego, CA 92093, USA.

Jin Zhang (J)

Department of Pharmacology, University of California, San Diego, San Diego, CA 92093, USA; Moores Cancer Center at UC San Diego Health, La Jolla, CA 92037, USA; Department of Bioengineering, University of California San Diego, San Diego, CA 92093; Department of Chemistry and Biochemistry, University of California San Diego, San Diego, CA 92093, USA.

Ruth T Yu (RT)

Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

Yang Dai (Y)

Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

Christopher Liddle (C)

Storr Liver Centre, Westmead Institute for Medical Research and Sydney Medical School, University of Sydney, Westmead, NSW, Australia.

Michael Downes (M)

Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

Ronald M Evans (RM)

Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

Steven A Kliewer (SA)

Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX 75390, USA.

David J Mangelsdorf (DJ)

Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute.

Alan R Saltiel (AR)

Department of Medicine, University of California, San Diego, San Diego, CA 92093, USA; Department of Pharmacology, University of California, San Diego, San Diego, CA 92093, USA. Electronic address: asaltiel@health.ucsd.edu.

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Classifications MeSH

questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Fibroblastes › Cellules 3T3 › Cellules Swiss 3T3 › Cellules 3T3-L1 › FGF21 promotes thermogenic gene expression as...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Adipocytes › FGF21 promotes thermogenic gene expression as...
questionsmedicales.fr › Tissus › Tissu conjonctif › Tissu adipeux › Tissu adipeux brun › FGF21 promotes thermogenic gene expression as...
questionsmedicales.fr › Tissus › Tissu conjonctif › Tissu adipeux › Tissu adipeux blanc › FGF21 promotes thermogenic gene expression as...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Agents neuromédiateurs › Agents adrénergiques › Agonistes adrénergiques › Agonistes bêta-adrénergiques › FGF21 promotes thermogenic gene expression as...
questionsmedicales.fr › Eucaryotes › Animaux › FGF21 promotes thermogenic gene expression as...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Communication cellulaire › Communication autocrine › FGF21 promotes thermogenic gene expression as...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Facteurs de croissance fibroblastique › FGF21 promotes thermogenic gene expression as...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › FGF21 promotes thermogenic gene expression as...
questionsmedicales.fr › Métabolisme › Métabolisme lipidique › Lipolyse › FGF21 promotes thermogenic gene expression as...
questionsmedicales.fr › Système digestif › Foie › FGF21 promotes thermogenic gene expression as...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › FGF21 promotes thermogenic gene expression as...
questionsmedicales.fr › Phénomènes physiologiques › Spécificité d'organe › FGF21 promotes thermogenic gene expression as...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › FGF21 promotes thermogenic gene expression as...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › FGF21 promotes thermogenic gene expression as...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs aux neuromédiateurs › Récepteurs catécholaminergiques › Récepteurs adrénergiques › Récepteurs bêta-adrénergiques › Récepteurs bêta-3 adrénergiques › FGF21 promotes thermogenic gene expression as...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur facteur croissance › Récepteur facteur croissance fibroblaste › FGF21 promotes thermogenic gene expression as...
questionsmedicales.fr › Phénomènes biologiques › Adaptation biologique › Adaptation physiologique › Régulation de la température corporelle › Thermogenèse › FGF21 promotes thermogenic gene expression as...