The evolving understanding of the contribution of lipid metabolism to diabetic
kidney disease.
Authors Stadler K, Goldberg IJ, Susztak K
Submitted By Krisztian Stadler on 6/9/2015
Status Published
Journal Current diabetes reports
Year 2015
Date Published 7/1/2015
Volume : Pages 15 : 611
PubMed Reference 25957525
Abstract Although diabetes is mainly diagnosed based on elevated glucose levels,
dyslipidemia is also observed in these patients. Chronic kidney disease (CKD), a
frequent occurrence in patients with diabetes, is associated with major
abnormalities in circulating lipoproteins and renal lipid metabolism. At
baseline, most renal epithelial cells rely on fatty acids as their energy
source. CKD, including that which occurs in diabetes, is characterized by tubule
epithelial lipid accumulation. Whether this is due to increased uptake or
greater local fatty acid synthesis is unknown. We have recently shown that CKD
also leads to decreased fatty acid oxidation, which might be an additional
mechanism leading to lipid accumulation. Defective fatty acid utilization causes
energy depletion resulting in increased apoptosis and dedifferentiation, which
in turn contributes to fibrosis and CKD progression. Enhanced fatty acid
oxidation in the kidney induced by fenofibrate, a peroxisomal
proliferator-activated receptor (PPAR)-a agonist, showed benefit in mouse models
of CKD. Fenofibrate treatment also reduced albuminuria in patients with diabetes
in multiple clinical trials. Taken together, these findings suggest that further
understanding of lipid metabolism in diabetic kidney disease may lead to novel
therapeutic approaches.

Investigators with authorship
Ira GoldbergNew York University School of Medicine
Krisztian StadlerPennington Biomedical Research Center
Katalin SusztakUniversity of Pennsylvania