VEGF–B is shown to have an unexpected role in targeting lipids to peripheral tissues. VEGF–B controls endothelial uptake of fatty acids via transcriptional regulation of vascular fatty acid transport proteins. Bioinformatic analyses suggest that the uptake of these lipids is tightly coupled with lipid use by mitochondria. Mice that do not have VEGF–B accumulate less lipids in muscle, heart and brown adipose tissue, and instead shunt them to white adipose tissue