PGC-1α Coordinates Mitochondrial Respiratory Capacity and Muscular Fatty Acid Uptake via Regulation of VEGF-B

Diabetes
Annika MehlemAnnelie Falkevall

Abstract

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 γ coactivator 1α (PGC-1α) together with estrogen-related receptor α (ERR-α) regulates expression of Vegfb Mice overexpressing PGC-1α under the muscle creatine kinase promoter (MPGC-1αTG mice) displayed increased Vegfb expression, and this was accompanied by increased muscular lipid accumulation. Ablation of Vegfb in MPGC-1αTG 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-1α overexpression and the development of the diabetes-like phenotype in HFD-fed MPGC-1αTG mice. The findings identify Vegfb as a novel gene regulated by the PGC-1α/ERR-α signaling pathway. Furthermore, the study highlights the role of PGC-1α as a master metabolic sensor that by regulating the expression levels of Vegfa and Vegfb coordinates blood v...Continue Reading

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Citations

Jan 15, 2017·Cardiovascular Diabetology·Jason Kar Sheng LewRajesh Katare
May 6, 2017·Parkinson's Disease·Beatrice CaballeroTorsten Falk
Nov 3, 2017·Cell Adhesion & Migration·Hongyu ZhuYue Tong
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May 8, 2018·Frontiers in Cardiovascular Medicine·Nathaniel LalBrian Rodrigues
Apr 16, 2020·International Journal of Molecular Sciences·Lucas Opazo-RíosJesús Egido
Apr 8, 2021·Journal of Muscle Research and Cell Motility·Ramzi A Al-HoraniMohammed Ihsan

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