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

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

doi:10.1038/s41467-020-16795-4

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

Nature communications, v.11 no.1 = v.11, 2020년, pp.2980 -

Bae, Hosung (Center for Vascular Research, Institute for Basic Science, Daejeon, 34141 Republic of Korea) , Hong, Ki Yong (Department of Plastic and Reconstructive Surgery, Dongguk University Ilsan Hospital, Goyang, 10326 Republic of Korea) , Lee, Choong-kun (Center for Vascular Research, Institute for Basic Science, Daejeon, 34141 Republic of Korea) , Jang, Cholsoon (Lewis Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Washington Rd, Princeton, NJ 08544 USA) , Lee, Seung-Jun (Center for Vascular Research, Institute for Basic Science, Daejeon, 34141 Republic of Korea) , Choe, Kibaek (Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141 Republic of Korea) , Offermanns, Stefan (Department of Pharmacology, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany) , He, Yulong (Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, 215123 Suzhou, China) , Lee, Hyuek Jong (Center for Vascular Research, Institute for Basic Science, Daejeon, 34141 Republic of Kore) , Koh, Gou Young

Abstract ▼ AI-Helper

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.Fat uptake and storage in subcutaneous adipose tissue (SAT) prevents ectopic fat accumulation and associated metabolic complications, however, the underlying mechanisms are incompletely understood. Here, the authors show that adipose angiopoietin-2 (Angpt2) enhances SAT size via increased endothelial fatty acid transport.

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