| First Author | Wang C | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 3 | Pages | 106272 |
| PubMed ID | 36915676 | Mgi Jnum | J:339213 |
| Mgi Id | MGI:7446049 | Doi | 10.1016/j.isci.2023.106272 |
| Citation | Wang C, et al. (2023) Smad4-mediated angiogenesis facilitates the beiging of white adipose tissue in mice. iScience 26(3):106272 |
| abstractText | Beige adipocytes are thermogenic with high expression of uncoupling protein 1 in the white adipose tissue (WAT), accompanied by angiogenesis. Previous studies showed that Smad4 is important for angiogenesis. Here we studied whether endothelial Smad4-mediated angiogenesis is involved in WAT beiging. Inducible knockout of endothelial cell (EC) selective Smad4 (Smad4 (iEC-KO)) was achieved by using the Smad4 (Floxp/floxp) and Tie2 (CreERT2) mice. Beige fat induction achieved by cold or adrenergic agonist, and angiogenesis were attenuated in WAT of Smad4 (iEC-KO) mice, with the less proliferation of ECs and adipogenic precursors. RNA sequencing of human ECs showed that Smad4 is involved in angiogenesis-related pathways. Knockdown of SMAD4 attenuated the upregulation of VEGFA, PDGFA, and angiogenesis in vitro. Treatment of human ECs with palmitic acid-induced Smad1/5 phosphorylation and the upregulation of core endothelial genes. Our study shows that endothelial Smad4 is involved in WAT beiging through angiogenesis and the expansion of adipose precursors into beige adipocytes. |
