Angiopoietin-2-integrin α5β1 signaling enhances vascular fatty acid transport and prevents ectopic lipid-induced insulin resistance
| Autor: | Yulong He, Seung Jun Lee, Cholsoon Jang, Stefan Offermanns, Kibaek Choe, Hosung Bae, Gou Young Koh, Hyuek Jong Lee, Choong-kun Lee, Ki Yong Hong |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
CD36 General Physics and Astronomy Inbred C57BL Cardiovascular Transgenic Mice 0302 clinical medicine 2.1 Biological and endogenous factors lcsh:Science Cells Cultured chemistry.chemical_classification Mice Knockout Multidisciplinary Cultured biology Chemistry Fatty Acids Diabetes Middle Aged Angiopoietin receptor Lipids Cell biology medicine.anatomical_structure Lipotoxicity Adipogenesis 5.1 Pharmaceuticals Female Fat metabolism Integrin alpha5beta1 Signal Transduction Adult Endothelium Transgene Science Cells Knockout Subcutaneous Fat Mice Transgenic General Biochemistry Genetics and Molecular Biology Article Angiopoietin-2 03 medical and health sciences Insulin resistance medicine Human Umbilical Vein Endothelial Cells Animals Humans Metabolic and endocrine Nutrition Gene Expression Profiling Prevention Fatty acid General Chemistry medicine.disease Lipid Metabolism Cardiovascular biology Mice Inbred C57BL 030104 developmental biology biology.protein lcsh:Q Insulin Resistance 030217 neurology & neurosurgery |
| Zdroj: | Nature communications, vol 11, iss 1 Nature Communications, Vol 11, Iss 1, Pp 1-17 (2020) Nature Communications |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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