Supporting Information Methods

VEGF-B KO rats. VEGF-B gene-deleted rats of Sprague-Dawley background were generated using a zinc-finger nuclease based technique by Sigma Advanced Genetic Engineering Labs, Sigma-Aldrich Biotechnology (St. Louis, Missouri, USA) (Cui et al, 2011; Geurts et al, 2009). A 22-base pair segment of exon 1 of the rat VEGF-B gene was replaced with a bacterial lacZ gene with a nuclear localization signal (Sheikh et al, 2008) (a kind gift from Thomas Quertermous) following the endogenous Kozak sequence (Supplemental Fig. 5). Two founder lines were obtained, and both were used for subsequent analyses. The model was verified by sequencing of the inserted lacZ and junctional regions as well as by quantitative PCR and RT-PCR for VEGF-B. The rats were genotyped by PCR of ear DNA with the primers 5’-CCATGGGACTCTGGCTGCC-3’ 5’GGTCTGCTTTCTGACAAACTCG-3’ and 5’-CACTTCCGCCAACCTTGAGAG-3’, of which the second targets the lacZ insert.