| First Author | Bae H | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 2980 |
| PubMed ID | 32532986 | Mgi Jnum | J:292186 |
| Mgi Id | MGI:6447534 | Doi | 10.1038/s41467-020-16795-4 |
| Citation | Bae H, et al. (2020) Angiopoietin-2-integrin alpha5beta1 signaling enhances vascular fatty acid transport and prevents ectopic lipid-induced insulin resistance. Nat Commun 11(1):2980 |
| abstractText | 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 alpha5beta1 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 alpha5beta1 signaling in the endothelium and triggered fatty acid transport via CD36 and FATP3 into SAT. Genetic or pharmacological inhibition of the endothelial integrin alpha5beta1 recapitulated adipocyte-specific Angpt2 knockout phenotypes. Our findings demonstrate the critical roles of Angpt2-integrin alpha5beta1 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. |
