Role of VEGF-B in fatty acid uptake and type-2 diabetes
Event details
| Date | 09.08.2012 |
| Hour | 10:30 › 11:30 |
| Speaker |
Carolina HAGBERG Karolinska Institutet, Dept of Molecular Biochemistry & Biophysics (MBB), Stockholm, Sweden |
| Location | |
| Category | Conferences - Seminars |
The prevalence of type-2 diabetes (T2D) is rapidly growing with severe socioeconomic impacts. Excess lipid accumulation can directly influence insulin sensitivity and glucose uptake in peripheral tissues, and has been proposed to be the underlying pathology of T2D. However, today only few treatment options exist that directly target ectopic lipid deposition. Recently we found that Vascular Endothelial Growth Factor B (VEGF-B), a member of the VEGFs, has an unexpected role in endothelial targeting of lipids to peripheral tissues (1). VEGF-B specifically controlled endothelial uptake of fatty acids via transcriptional regulation of vascular fatty acid transport proteins. As a consequence, VEGF-B-/- mice displayed less uptake and accumulation of lipids in muscle and heart, and instead shunted lipids to white adipose tissue. Similarly, genetic deletion of Vegfb in rodent models of insulin resistance and T2D prevented ectopic lipid deposition, increased muscular glucose uptake and improved glucose tolerance (2). Pharmacological inhibition of VEGF-B signalling by antibody administration to diabetic db/db mice enhanced glucose tolerance, improved pancreatic function and ameliorated dyslipidaemia, key elements of the metabolic syndrome. Our results demonstrate that the vascular endothelium can function as an efficient barrier towards excess muscular lipid uptake even under conditions of severe obesity and T2D, and that this barrier can be maintained by inhibition of VEGF-B signalling. We propose that VEGF-B antagonism is a novel pharmacological approach for T2D, targeting the lipid-transport properties of the endothelium in order to improve muscular insulin sensitivity and glucose disposal.
1. Hagberg CE, Falkevall A, Wang X, Larsson E, Huusko J, Nilsson I, van Meeteren LA, Samen E, Lu L, Vanwildemeersch M, Klar J, Genove G, Pietras K, Stone-Elander S, Claesson-Welsh L, Yla-Herttuala S, Lindahl P, and Eriksson U. Vascular endothelial growth factor B controls endothelial fatty acid uptake. Nature 464: 917-921, 2010.
2. Hagberg CE*, Mehlem A*, Falkevall A, Muhl L, Fam BC, Ortsäter H, Scotney P, Samen E, Lu L, Stone-Elander S, Proietto J, Andrikopoulos S, Sjöholm Å, Nash A, Eriksson U. Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes. *These authors contributed equally to this work. Manuscript under revision.
1. Hagberg CE, Falkevall A, Wang X, Larsson E, Huusko J, Nilsson I, van Meeteren LA, Samen E, Lu L, Vanwildemeersch M, Klar J, Genove G, Pietras K, Stone-Elander S, Claesson-Welsh L, Yla-Herttuala S, Lindahl P, and Eriksson U. Vascular endothelial growth factor B controls endothelial fatty acid uptake. Nature 464: 917-921, 2010.
2. Hagberg CE*, Mehlem A*, Falkevall A, Muhl L, Fam BC, Ortsäter H, Scotney P, Samen E, Lu L, Stone-Elander S, Proietto J, Andrikopoulos S, Sjöholm Å, Nash A, Eriksson U. Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes. *These authors contributed equally to this work. Manuscript under revision.
Practical information
- General public
- Free
Organizer
- Kristina Schoonjans et Johan Auwerx
Contact
- Johan Auwerx