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The Vitamin D Receptor Agonist Doxercalciferol Modulates Dietary Fat Induced Renal Disease and Renal Lipid Metabolism

Authors Wang XX, Jiang T, Shen Y, Santamaria H, Solis N, Arbeeny CM, Levi M Submitted By Moshe Levi on 1/17/2011 Status Published Journal American journal of physiology. Renal physiology Year 2011 Date Published 3/1/2011 Volume : Pages Not Specified : Not Specified PubMed Reference 21209008 Abstract Diet induced obesity (DIO) and insulin resistance in mice is associated with proteinuria, renal mesangial expansion, accumulation of extracellular matrix proteins, and activation of oxidative stress, proinflammatory cytokines, profibrotic growth factors, and the sterol regulatory element binding proteins, SREBP-1 and SREBP-2 that mediate increases in fatty acid and cholesterol synthesis. The purpose of the present study was to determine if treatment of DIO mice with the vitamin D receptor (VDR) agonist doxercalciferol (1a-hydroxyvitamin D2) prevents renal disease. Our results indicate that treatment of DIO mice with the VDR agonist decreases proteinuria, podocyte injury, mesangial expansion, and extracellular matrix protein accumulation. The VDR agonist also decreases macrophage infiltration, oxidative stress, proinflammatory cytokines and profibrotic growth factors. Furthermore the VDR agonist also prevents the activation of the renin angiotensin aldosterone system including the Angiotensin II type 1 Receptor (AT1R) and the Mineralocorticoid Receptor (MR). An additional novel finding of our study is that activation of VDR results in decreased accumulation of neutral lipids (triglycerides and cholesterol) and expression of adipophilin in the kidney by decreasing SREBP-1 and SREBP-2 expression and target enzymes that mediate fatty acid and cholesterol synthesis and increasing expression of the farnesoid X receptor (FXR). This study therefore demonstrates multiple novel effects of VDR activation in the kidney which prevent renal manifestations of diet induced obesity in the kidney.

Investigators with authorship
Name Institution Moshe Levi Georgetown University

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