Murine double minute-2 mediates exercise-induced angiogenesis in adipose tissue of diet-induced obese mice.
Adipocytes, Brown
/ metabolism
Adipocytes, White
/ metabolism
Adipose Tissue, White
/ blood supply
Animals
Cellular Microenvironment
Diet, High-Fat
Disease Models, Animal
Exercise Therapy
Forkhead Box Protein O1
/ metabolism
Forkhead Box Protein O3
/ metabolism
Male
Mice, Inbred C57BL
Neovascularization, Physiologic
Obesity
/ metabolism
Proto-Oncogene Proteins c-mdm2
/ metabolism
Signal Transduction
Thrombospondin 1
/ metabolism
Tissue Culture Techniques
Vascular Endothelial Growth Factor A
/ metabolism
Weight Loss
Adipose tissue
Angiogenesis
Browning
FoxO-1
Inflammation
Mdm-2
Physical activity
Journal
Microvascular research
ISSN: 1095-9319
Titre abrégé: Microvasc Res
Pays: United States
ID NLM: 0165035
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
07
11
2019
revised:
06
02
2020
accepted:
16
03
2020
pubmed:
23
3
2020
medline:
24
9
2020
entrez:
23
3
2020
Statut:
ppublish
Résumé
This study aimed to determine the effects of physical exercise on the angio-adaptive response in adipose tissue following weight loss in a mouse model of diet-induced obesity. We hypothesized that physical exercise stimulates angiogenesis through the regulation of Vascular endothelial growth factor-A (VEGF-A) pro-/Thrombospondin-1 (TSP-1) anti-angiogenic signal under the control of the Murine double-minute 2/Forkhead box Os (Mdm2/FoxOs) axis, as reported in skeletal muscle. We studied the effects of 7 weeks-voluntary exercise (Ex) in C57Bl/6 control or diet-induced obese (HFS) mice on vascularization of white adipose tissue (AT). Diet-induced obese sedentary (HFSsed) mice presented a powerful angiostatic control in all adipose tissues, under FoxOs protein regulation, leading to capillary rarefaction. Exercise increased expression of Mdm2, repressing the angiostatic control in favor of adipose vascular regrowth in normal chow (NCex) and HFSex mice. This phenomenon was associated with adipocytes microenvironment improvement, such as decreased adipocytes hypertrophy and adipose tissue inflammation. In addition, adipose angiogenesis stimulation by exercise through Mdm2 pro-angiogenic action, improved visceral adipose insulin sensitivity, activated browning process within subcutaneous adipose tissue (ScWAT) and decreased ectopic fat deposition (muscle, heart and liver) in obese HFSex mice. The overall result of this approach of therapy by physical exercise is an improvement of all systemic cardiometabolic parameters. These data demonstrated the therapeutic efficacy of physical exercise against obesity-associated pathologies, and also offer new prospects for molecular therapies targeting the adipose angio-adaptation in obese humans.
Identifiants
pubmed: 32199946
pii: S0026-2862(20)30063-7
doi: 10.1016/j.mvr.2020.104003
pii:
doi:
Substances chimiques
Forkhead Box Protein O1
0
Forkhead Box Protein O3
0
FoxO3 protein, mouse
0
Foxo1 protein, mouse
0
Thrombospondin 1
0
Vascular Endothelial Growth Factor A
0
Thbs1 protein, mouse
0
vascular endothelial growth factor A, mouse
0
Mdm2 protein, mouse
EC 2.3.2.27
Proto-Oncogene Proteins c-mdm2
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104003Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors have no potential conflicts of interest.