Fibro-Adipogenic Remodeling of the Diaphragm in Obesity-Associated Respiratory Dysfunction.
Journal
Diabetes
ISSN: 1939-327X
Titre abrégé: Diabetes
Pays: United States
ID NLM: 0372763
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
19
02
2018
accepted:
03
10
2018
pubmed:
27
10
2018
medline:
26
3
2019
entrez:
27
10
2018
Statut:
ppublish
Résumé
Respiratory dysfunction is a common complication of obesity, conferring cardiovascular morbidity and increased mortality and often necessitating mechanical ventilatory support. While impaired lung expansion in the setting of increased adipose mass and reduced central response to hypercapnia have been implicated as pathophysiological drivers, the impact of obesity on respiratory muscles-in particular, the diaphragm-has not been investigated in detail. Here, we demonstrate that chronic high-fat diet (HFD) feeding impairs diaphragm muscle function, as assessed in vivo by ultrasonography and ex vivo by measurement of contractile force. During an HFD time course, progressive adipose tissue expansion and collagen deposition within the diaphragm parallel contractile deficits. Moreover, intradiaphragmatic fibro-adipogenic progenitors (FAPs) proliferate with long-term HFD feeding while giving rise to adipocytes and type I collagen-depositing fibroblasts. Thrombospondin 1 (THBS1), a circulating adipokine, increases with obesity and induces FAP proliferation. These findings suggest a novel role for FAP-mediated fibro-adipogenic diaphragm remodeling in obesity-associated respiratory dysfunction.
Identifiants
pubmed: 30361289
pii: db18-0209
doi: 10.2337/db18-0209
pmc: PMC6302533
doi:
Substances chimiques
Collagen
9007-34-5
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
45-56Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK095137
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL147377
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007696
Pays : United States
Organisme : NIH HHS
ID : K26 OD016502
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR069620
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020572
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR068428
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2018 by the American Diabetes Association.
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