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Cited by 52Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismCardiovascular Disease and Adiposity

Angiopoietin-2–integrin α5β1 signaling enhances vascular fatty acid transport and prevents ectopic lipid-induced insulin resistance

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Bae, Hosung, Hong, Ki Yong, Lee, Choong-kun, Jang, Cholsoon, Lee, Seung-Jun, Choe, Kibaek, Offermanns, Stefan, He, Yulong +2 more·2020·Nature Communications
DOI 10.1038/s41467-020-16795-4PMC PMC7293240
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Abstract

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.

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Authors
Bae, H., Hong, K. Y., Lee, C.-K., Jang, C., Lee, S.-J., Choe, K., Offermanns, S., He, Y., Lee, H. J., & Koh, G. Y.
Affiliations
  • Institute for Basic Science (KR)
  • Dongguk University Ilsan Hospital (KR)
  • Korea Advanced Institute of Science and Technology (KR)
  • Princeton University (US)
  • Max Planck Institute for Heart and Lung Research (DE)
  • Soochow University (CN)
Corresponding author
  • He, Yulong
  • Koh, Gou Young
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2020-06-12
Volume
11
Issue
1
Pages
2980-2980
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-020-16795-4
PMC
PMC7293240
OpenAlex
W3034871512
Cited by
52
References
14
Citations by year
2026: 7 · 2025: 7 · 2024: 9 · 2023: 6 · 2022: 11 · 2021: 9 · 2020: 3
FWCI
5.20
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
Ministry of Science, ICT and Future Planning (IBS-R025-D1)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
Keywords
angiopoietin-2, alpha5beta1 integrin, fatty acid uptake, subcutaneous adipose tissue, ectopic fat deposition, insulin resistance, CD36, endothelial signaling, body fat distribution, lipotoxicity, skeletal muscle, liver
MeSH terms
Adult, Animals, Cells, Cultured, Fatty Acids, Female, Humans, Insulin Resistance, Lipids, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Signal Transduction, Mice, Knockout, Gene Expression Profiling, Integrin alpha5beta1, Angiopoietin-2, Subcutaneous Fat, Lipid Metabolism, Human Umbilical Vein Endothelial Cells

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