Defective extracellular matrix remodeling in brown adipose tissue is associated with fibro-inflammation and reduced diet-induced thermogenesis.
CP: Metabolism
PEPD
brown adipose tissue
extracellular matrix
fibrosis
obesity
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
27 06 2023
27 06 2023
Historique:
received:
03
01
2023
revised:
25
04
2023
accepted:
29
05
2023
medline:
4
10
2023
pubmed:
15
6
2023
entrez:
15
6
2023
Statut:
ppublish
Résumé
The relevance of extracellular matrix (ECM) remodeling is reported in white adipose tissue (AT) and obesity-related dysfunctions, but little is known about the importance of ECM remodeling in brown AT (BAT) function. Here, we show that a time course of high-fat diet (HFD) feeding progressively impairs diet-induced thermogenesis concomitantly with the development of fibro-inflammation in BAT. Higher markers of fibro-inflammation are associated with lower cold-induced BAT activity in humans. Similarly, when mice are housed at thermoneutrality, inactivated BAT features fibro-inflammation. We validate the pathophysiological relevance of BAT ECM remodeling in response to temperature challenges and HFD using a model of a primary defect in the collagen turnover mediated by partial ablation of the Pepd prolidase. Pepd-heterozygous mice display exacerbated dysfunction and BAT fibro-inflammation at thermoneutrality and in HFD. Our findings show the relevance of ECM remodeling in BAT activation and provide a mechanism for BAT dysfunction in obesity.
Identifiants
pubmed: 37318951
pii: S2211-1247(23)00651-4
doi: 10.1016/j.celrep.2023.112640
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
112640Subventions
Organisme : Medical Research Council
ID : MC_UU_00014/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12012/5
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 222748/Z/21/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 10953/Z/15/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12012/2
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 100574/Z/12/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00014/5
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/18/7/33636
Pays : United Kingdom
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.