한빛사 논문
Hosung Bae1, Ki Yong Hong2, Choong-kun Lee1,3, Cholsoon Jang4,8, Seung-Jun Lee1, Kibaek Choe5, Stefan Offermanns6, Yulong He7,*, Hyuek Jong Lee1 & Gou Young Koh1,3,*
1Center for Vascular Research, Institute for Basic Science, Daejeon 34141, Republic of Korea.
2Department of Plastic and Reconstructive Surgery, Dongguk University Ilsan Hospital, Goyang 10326, Republic of Korea.
3Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
4Lewis Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Washington Rd, Princeton, NJ 08544, USA.
5Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology(KAIST), Daejeon 34141, Republic of Korea.
6Department of Pharmacology, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
7Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, 215123 Suzhou, China.
8Present address: Department of Biological Chemistry, University of California Irvine, 92697 Irvine, CA, US.
*Corresponding author
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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