Reducing VEGF-B Signaling Ameliorates Renal Lipotoxicity and Protects against Diabetic Kidney Disease
2017 (English)In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 25, no 3, 713-726 p.Article in journal (Refereed) Published
Diabetic kidney disease (DKD) is the most common cause of severe renal disease, and few treatment options are available today that prevent the progressive loss of renal function. DKD is characterized by altered glomerular filtration and proteinuria. A common observation in DKD is the presence of renal steatosis, but the mechanism(s) underlying this observation and to what extent they contribute to disease progression are unknown. Vascular endothelial growth factor B (VEGF-B) controls muscle lipid accumulation through regulation of endothelial fatty acid transport. 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.
Place, publisher, year, edition, pages
2017. Vol. 25, no 3, 713-726 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-318926DOI: 10.1016/j.cmet.2017.01.004ISI: 000396355700026PubMedID: 28190774OAI: oai:DiVA.org:uu-318926DiVA: diva2:1087062
FunderSwedish Heart Lung Foundation, 20110451, 20120077Swedish Research Council, 2011-03861Swedish Cancer Society, CAN 2011/792, CAN 2014/630