Here, we demonstrate in experimental mouse models of DKD that renal VEGF-B expression correlates with the severity of disease. Inhibiting VEGF-B signaling in DKD mouse models reduces renal lipotoxicity, re-sensitizes podocytes to insulin signaling, inhibits the development of DKD-associated pathologies, and prevents renal dysfunction. Further, we show that elevated VEGF-B levels are found in patients with DKD, suggesting that VEGF-B antagonism represents a novel approach to treat DKD.

Type 2 diabetes is a chronic disease that affects more than 310 million people worldwide, about 90% of whom display insulin resistance. This study demonstrates, in several animal models of type 2 diabetes, that genetic and pharmacological inhibition of signalling by vascular endothelial growth factor B (VEGF-B) can limit the accumulation of fats in the muscles and reverse adverse metabolic consequences of type 2 diabetes, including insulin resistance.

VEGF-B, a vascular endothelial growth factor that is highly expressed in heart, skeletal muscle and brown adipose tissue, has been found to have an unexpected role in targeting lipids to peripheral tissues. Mice lacking VEGF-B accumulate lower amounts of lipids in muscle, heart and brown adipose tissue, and instead shunt them to white adipose tissue. The involvement of VEGF-B in redistributing lipids suggest possible novel strategies for modulating lipid accumulation in diabetes, obesity and cardiovascular diseases.