| First Author | Mehlem A | Year | 2016 |
| Journal | Diabetes | Volume | 65 |
| Issue | 4 | Pages | 861-73 |
| PubMed ID | 26822083 | Mgi Jnum | J:246628 |
| Mgi Id | MGI:5924773 | Doi | 10.2337/db15-1231 |
| Citation | Mehlem A, et al. (2016) PGC-1alpha Coordinates Mitochondrial Respiratory Capacity and Muscular Fatty Acid Uptake via Regulation of VEGF-B. Diabetes 65(4):861-73 |
| abstractText | Vascular endothelial growth factor (VEGF) B belongs to the VEGF family, but in contrast to VEGF-A, VEGF-B does not regulate blood vessel growth. Instead, VEGF-B controls endothelial fatty acid (FA) uptake and was identified as a target for the treatment of type 2 diabetes. The regulatory mechanisms controlling Vegfb expression have remained unidentified. We show that peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) together with estrogen-related receptor alpha (ERR-alpha) regulates expression of Vegfb Mice overexpressing PGC-1alpha under the muscle creatine kinase promoter (MPGC-1alphaTG mice) displayed increased Vegfb expression, and this was accompanied by increased muscular lipid accumulation. Ablation of Vegfb in MPGC-1alphaTG mice fed a high-fat diet (HFD) normalized glucose intolerance, insulin resistance, and dyslipidemia. We suggest that VEGF-B is the missing link between PGC-1alpha overexpression and the development of the diabetes-like phenotype in HFD-fed MPGC-1alphaTG mice. The findings identify Vegfb as a novel gene regulated by the PGC-1alpha/ERR-alpha signaling pathway. Furthermore, the study highlights the role of PGC-1alpha as a master metabolic sensor that by regulating the expression levels of Vegfa and Vegfb coordinates blood vessel growth and FA uptake with mitochondrial FA oxidation. |
