FGF15/19 is required for adipose tissue plasticity in response to thermogenic adaptations.
Adipose Tissue
/ metabolism
Adipose Tissue, Brown
/ metabolism
Adipose Tissue, White
/ metabolism
Animals
Female
Fibroblast Growth Factors
/ genetics
Humans
Insulin
/ metabolism
Insulin Resistance
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Obesity
/ metabolism
Thermogenesis
/ physiology
Uncoupling Protein 1
/ metabolism
Adipose tissue plasticity
Browning
Enterokine
Fibroblast Growth Factor 15
Fibroblast Growth Factor 19
Journal
Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
20
08
2020
revised:
02
11
2020
accepted:
04
11
2020
pubmed:
11
11
2020
medline:
31
8
2021
entrez:
10
11
2020
Statut:
ppublish
Résumé
To determine the role of enterokine FGF15/19 in adipose tissue thermogenic adaptations. Circulating FGF19 and gene expression (qRT-PCR) levels were assessed in subcutaneous adipose tissue from obese human patients. Effects of experimentally increased FGF15 and FGF19 levels in vivo were determined in mice using adenoviral and adeno-associated vectors. Adipose tissues were characterized in FGF15-null mice under distinct cold-related thermogenic challenges. The analyses spanned metabolic profiling, tissue characterization, histology, gene expression, and immunoblot assays. In humans, FGF19 levels are directly associated with UCP1 gene expression in subcutaneous adipose tissue. Experimental increases in FGF15 or FGF19 induced white fat browning in mice as demonstrated by the appearance of multilocular beige cells and markers indicative of a beige phenotype, including increased UCP1 protein levels. Mice lacking FGF15 showed markedly impaired white adipose tissue browning and a mild reduction in parameters indicative of BAT activity in response to cold-induced environmental thermogenic challenges. This was concomitant with signs of altered systemic metabolism, such as reduced glucose tolerance and impaired cold-induced insulin sensitization. Enterokine FGF15/19 is a key factor required for adipose tissue plasticity in response to thermogenic adaptations.
Identifiants
pubmed: 33171307
pii: S2212-8778(20)30187-3
doi: 10.1016/j.molmet.2020.101113
pmc: PMC7691747
pii:
doi:
Substances chimiques
FGF19 protein, human
0
Insulin
0
Uncoupling Protein 1
0
fibroblast growth factor 15, mouse
0
Fibroblast Growth Factors
62031-54-3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101113Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.
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