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SUMMARY:Role of VEGF-B in fatty acid uptake and type-2 diabetes
DTSTART:20120809T103000
DTEND:20120809T113000
DTSTAMP:20260916T044009Z
UID:2da27741409267b3699a309d535d1dbe40129bd89a1d523765d3243a
CATEGORIES:Conferences - Seminars
DESCRIPTION:Carolina HAGBERG\nKarolinska Institutet\, Dept of Molecular Bi
 ochemistry & Biophysics (MBB)\, Stockholm\, Sweden\nThe prevalence of type
 -2 diabetes (T2D) is rapidly growing with severe socioeconomic impacts. Ex
 cess lipid accumulation can directly influence insulin sensitivity and glu
 cose uptake in peripheral tissues\, and has been proposed to be the underl
 ying pathology of T2D. However\, today only few treatment options exist th
 at directly target ectopic lipid deposition. Recently we found that Vascul
 ar Endothelial Growth Factor B (VEGF-B)\, a member of the VEGFs\, has an u
 nexpected role in endothelial targeting of lipids to peripheral tissues (1
 ). VEGF-B specifically controlled endothelial uptake of fatty acids via tr
 anscriptional regulation of vascular fatty acid transport proteins. As a c
 onsequence\, VEGF-B-/- mice displayed less uptake and accumulation of lipi
 ds in muscle and heart\, and instead shunted lipids to white adipose tissu
 e. Similarly\, genetic deletion of Vegfb in rodent models of insulin resis
 tance and T2D prevented ectopic lipid deposition\, increased muscular gluc
 ose uptake and improved glucose tolerance (2). Pharmacological inhibition 
 of VEGF-B signalling by antibody administration to diabetic db/db mice enh
 anced glucose tolerance\, improved pancreatic function and ameliorated dys
 lipidaemia\, key elements of the metabolic syndrome. Our results demonstra
 te that the vascular endothelium can function as an efficient barrier towa
 rds excess muscular lipid uptake even under conditions of severe obesity a
 nd T2D\, and that this barrier can be maintained by inhibition of VEGF-B s
 ignalling. We propose that VEGF-B antagonism is a novel pharmacological ap
 proach for T2D\, targeting the lipid-transport properties of the endotheli
 um in order to improve muscular insulin sensitivity and glucose disposal.\
 n\n1. 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\, Lin
 dahl P\, and Eriksson U. Vascular endothelial growth factor B controls end
 othelial fatty acid uptake. Nature 464: 917-921\, 2010.\n2. Hagberg CE*\, 
 Mehlem A*\, Falkevall A\, Muhl L\, Fam BC\, Ortsäter H\, Scotney P\, Same
 n 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 r
 esistance and type 2 diabetes. *These authors contributed equally to this 
 work. Manuscript under revision.
LOCATION:AI 1153 https://plan.epfl.ch/?room==AI%201153
STATUS:CONFIRMED
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