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

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

doi:10.1038/s41467-020-16795-4

Back

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

Journal article

Peer reviewed

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

Hosung Bae, Ki Yong Hong, Choong-Kun Lee, Cholsoon Jang, Seung-Jun Lee, Kibaek Choe, Stefan Offermanns, Yulong He, Hyuek Jong Lee and Gou Young Koh

Nature communications, Vol.11(1), pp.2980-17

06/12/2020

DOI: 10.1038/s41467-020-16795-4

PMID: 32532986

Files and links (1)

url

https://doi.org/10.1038/s41467-020-16795-4View

Published (Version of record) Open Access

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.

Adult

Angiopoietin-2 - genetics

Angiopoietin-2 - metabolism

Animals

Cells, Cultured

Fatty Acids - metabolism

Female

Gene Expression Profiling - methods

Human Umbilical Vein Endothelial Cells - cytology

Human Umbilical Vein Endothelial Cells - metabolism

Humans

Insulin Resistance - genetics

Insulin Resistance - physiology

Integrin alpha5beta1 - genetics

Integrin alpha5beta1 - metabolism

Lipid Metabolism - genetics

Lipid Metabolism - physiology

Lipids - analysis

Mice, Inbred C57BL

Mice, Knockout

Mice, Transgenic

Middle Aged

Signal Transduction - genetics

Subcutaneous Fat - metabolism

Details

Title: Subtitle: Angiopoietin-2-integrin α5β1 signaling enhances vascular fatty acid transport and prevents ectopic lipid-induced insulin resistance
Creators: Hosung Bae - Institute for Basic Science
Ki Yong Hong - Dongguk University Ilsan Hospital
Choong-Kun Lee - Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea
Cholsoon Jang - University of California, Irvine
Seung-Jun Lee - Institute for Basic Science
Kibaek Choe - Korea Advanced Institute of Science and Technology
Stefan Offermanns - Max Planck Institute for Heart and Lung Research
Yulong He - Soochow University
Hyuek Jong Lee - Institute for Basic Science
Gou Young Koh - Korea Advanced Institute of Science and Technology
Resource Type: Journal article
Publication Details: Nature communications, Vol.11(1), pp.2980-17
DOI: 10.1038/s41467-020-16795-4
PMID: 32532986
ISSN: 2041-1723
eISSN: 2041-1723
Language: English
Date published: 06/12/2020
Academic Unit: Internal Medicine
Record Identifier: 9985217136502771

Metrics

1 Record Views

38 Times Cited - Web of Science