The farnesoid X receptor modulates renal lipid metabolism and diet-induced renal
inflammation, fibrosis, and proteinuria.
Authors Wang XX, Jiang T, Shen Y, Adorini L, Pruzanski M, Gonzalez FJ, Scherzer P, Lewis
L, Miyazaki-Anzai S, Levi M
Submitted By Moshe Levi on 3/24/2010
Status Published
Journal American journal of physiology. Renal physiology
Year 2009
Date Published 12/1/2009
Volume : Pages 297(6) : F1587 - F1596
PubMed Reference 19776172
Abstract Diet-induced obesity is associated with proteinuria and glomerular disease in
humans and rodents. We have shown that in mice fed a high-fat diet, increased
renal expression of the transcriptional factor sterol-regulatory element binding
protein-1 (SREBP-1) plays a critical role in renal lipid accumulation and
increases the activity of proinflammatory cytokines and profibrotic growth
factors. In the current study, we have determined a key role of the farnesoid X
receptor (FXR) in modulating renal SREBP-1 activity, glomerular lesions, and
proteinuria. We found that feeding a Western-style diet to DBA/2J mice results
in proteinuria, podocyte loss, mesangial expansion, renal lipid accumulation,
and increased expression of proinflammatory factors, oxidative stress, and
profibrotic growth factors. Treatment of these mice with the highly selective
and potent FXR-activating ligand 6-alpha-ethyl-chenodeoxycholic acid (INT-747)
ameliorates triglyceride accumulation by modulating fatty acid synthesis and
oxidation, improves proteinuria, prevents podocyte loss, mesangial expansion,
accumulation of extracellular matrix proteins, and increased expression of
profibrotic growth factors and fibrosis markers, and modulates inflammation and
oxidative stress. Our results therefore indicate that FXR activation could
represent an effective therapy for treatment of abnormal renal lipid metabolism
with associated inflammation, oxidative stress, and kidney pathology in patients
affected by obesity.

Investigators with authorship
Moshe LeviGeorgetown University


Nr1h4nuclear receptor subfamily 1, group H, member 4
Srebf1sterol regulatory element binding factor 1