Angiopoietin-2-integrin α5β1 signaling enhances vascular fatty acid transport and prevents ectopic lipid-induced insulin resistance.
Adult
Angiopoietin-2
/ genetics
Animals
Cells, Cultured
Fatty Acids
/ metabolism
Female
Gene Expression Profiling
/ methods
Human Umbilical Vein Endothelial Cells
/ cytology
Humans
Insulin Resistance
/ genetics
Integrin alpha5beta1
/ genetics
Lipid Metabolism
/ genetics
Lipids
/ analysis
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Middle Aged
Signal Transduction
/ genetics
Subcutaneous Fat
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 06 2020
12 06 2020
Historique:
received:
28
05
2019
accepted:
22
05
2020
entrez:
14
6
2020
pubmed:
14
6
2020
medline:
25
8
2020
Statut:
epublish
Résumé
Proper storage of excessive dietary fat into subcutaneous adipose tissue (SAT) prevents ectopic lipid deposition-induced insulin resistance, yet the underlying mechanism remains unclear. Here, we identify angiopoietin-2 (Angpt2)-integrin α5β1 signaling as an inducer of fat uptake specifically in SAT. Adipocyte-specific deletion of Angpt2 markedly reduced fatty acid uptake and storage in SAT, leading to ectopic lipid accumulation in glucose-consuming organs including skeletal muscle and liver and to systemic insulin resistance. Mechanistically, Angpt2 activated integrin α5β1 signaling in the endothelium and triggered fatty acid transport via CD36 and FATP3 into SAT. Genetic or pharmacological inhibition of the endothelial integrin α5β1 recapitulated adipocyte-specific Angpt2 knockout phenotypes. Our findings demonstrate the critical roles of Angpt2-integrin α5β1 signaling in SAT endothelium in regulating whole-body fat distribution for metabolic health and highlight adipocyte-endothelial crosstalk as a potential target for prevention of ectopic lipid deposition-induced lipotoxicity and insulin resistance.
Identifiants
pubmed: 32532986
doi: 10.1038/s41467-020-16795-4
pii: 10.1038/s41467-020-16795-4
pmc: PMC7293240
doi:
Substances chimiques
Angiopoietin-2
0
Angpt2 protein, mouse
0
Fatty Acids
0
Integrin alpha5beta1
0
Lipids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2980Références
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