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
Moshe LeviGeorgetown University