Hepatic AKT orchestrates adipose tissue thermogenesis via FGF21-dependent and -independent mechanisms.

Adipose Tissue, Brown / metabolism Adipose Tissue, White / metabolism Animals Fibroblast Growth Factors / metabolism Liver / pathology Mice Proto-Oncogene Proteins c-akt / metabolism Thermogenesis / genetics
FGF21 FOXO1 cold sensitivity lipolysis liver insulin signaling thermogenesis

Journal

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

Informations de publication

Date de publication:
18 05 2021
Historique:
received: 09 07 2020
revised: 02 04 2021
accepted: 22 04 2021
entrez: 19 5 2021
pubmed: 20 5 2021
medline: 10 2 2022
Statut: ppublish

Résumé

Organismal stressors such as cold exposure require a systemic response to maintain body temperature. Brown adipose tissue (BAT) is a key thermogenic tissue in mammals that protects against hypothermia in response to cold exposure. Defining the complex interplay of multiple organ systems in this response is fundamental to our understanding of adipose tissue thermogenesis. In this study, we identify a role for hepatic insulin signaling via AKT in the adaptive response to cold stress and show that liver AKT is an essential cell-nonautonomous regulator of adipocyte lipolysis and BAT function. Mechanistically, inhibition of forkhead box O1 (FOXO1) by AKT controls BAT thermogenesis by enhancing catecholamine-induced lipolysis in the white adipose tissue (WAT) and increasing circulating fibroblast growth factor 21 (FGF21). Our data identify a role for hepatic insulin signaling via the AKT-FOXO1 axis in regulating WAT lipolysis, promoting BAT thermogenic capacity, and ensuring a proper thermogenic response to acute cold exposure.

Identifiants

DOI: 10.1016/j.celrep.2021.109128 PMID: 34010646 PMC: PMC8167823
pubmed: 34010646
pii: S2211-1247(21)00467-8
doi: 10.1016/j.celrep.2021.109128
pmc: PMC8167823
mid: NIHMS1706268
pii:
doi:

Substances chimiques

fibroblast growth factor 21 0
Fibroblast Growth Factors 62031-54-3
Proto-Oncogene Proteins c-akt EC 2.7.11.1

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

109128

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK125497
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK054759
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK123252
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK106104
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007314
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK019525
Pays : United States

Informations de copyright

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

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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Auteurs

Jaimarie Sostre-Colón (J)

Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Kahealani Uehara (K)

Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Anna E Garcia Whitlock (AE)

Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Matthew J Gavin (MJ)

Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Jeff Ishibashi (J)

Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Matthew J Potthoff (MJ)

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.

Patrick Seale (P)

Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Paul M Titchenell (PM)

Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Physiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: ptitc@pennmedicine.upenn.edu.

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Classifications MeSH

questionsmedicales.fr › Tissus › Tissu conjonctif › Tissu adipeux › Tissu adipeux brun › Hepatic AKT orchestrates adipose tissue...
questionsmedicales.fr › Tissus › Tissu conjonctif › Tissu adipeux › Tissu adipeux blanc › Hepatic AKT orchestrates adipose tissue...
questionsmedicales.fr › Eucaryotes › Animaux › Hepatic AKT orchestrates adipose tissue...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Facteurs de croissance fibroblastique › Hepatic AKT orchestrates adipose tissue...
questionsmedicales.fr › Système digestif › Foie › Hepatic AKT orchestrates adipose tissue...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Hepatic AKT orchestrates adipose tissue...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines proto-oncogènes › Protéines proto-oncogènes c-akt › Hepatic AKT orchestrates adipose tissue...
questionsmedicales.fr › Phénomènes biologiques › Adaptation biologique › Adaptation physiologique › Régulation de la température corporelle › Thermogenèse › Hepatic AKT orchestrates adipose tissue...