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Bae, Hosung
혈관 연구단
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Angiopoietin-2–integrin α5β1 signaling enhances vascular fatty acid transport and prevents ectopic lipid-induced insulin resistance

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Title
Angiopoietin-2–integrin α5β1 signaling enhances vascular fatty acid transport and prevents ectopic lipid-induced insulin resistance
Author(s)
Hosung Bae; Ki Yong Hong; Choong-kun Lee; Cholsoon Jang; Seung-Jun Lee; Kibaek Choe; Stefan Offermanns; Yulong He; Hyuek Jong Lee; Gou Young Koh
Subject
VEGF-B, ; ANGIOGENESIS, ; EXPRESSION, ; OBESITY, ; ADIPOGENESIS, ; ACTIVATION, ; EXPANSION, ; POLARITY, ; CELLS, ; TIE2
Publication Date
2020-06
Journal
NATURE COMMUNICATIONS, v.11, no.1, pp.2980
Publisher
NATURE PUBLISHING GROUP
Abstract
© 2020, The Author(s). 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
URI
https://pr.ibs.re.kr/handle/8788114/7833
DOI
10.1038/s41467-020-16795-4
ISSN
2041-1723
Appears in Collections:
Center for Vascular Research(혈관 연구단) > 1. Journal Papers (저널논문)
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