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PPAR Research
Volume 2010 (2010), Article ID 703735, 9 pages
Review Article

Regulation of ENaC-Mediated Sodium Reabsorption by Peroxisome Proliferator-Activated Receptors

1Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
2Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
3Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA
4Kidney Disease Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA

Received 6 January 2010; Revised 16 March 2010; Accepted 14 April 2010

Academic Editor: Tianxin Yang

Copyright © 2010 Tengis S. Pavlov et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Peroxisome proliferator-activated receptors (PPARs) are members of a steroid hormone receptor superfamily that responds to changes in lipid and glucose homeostasis. Peroxisomal proliferator-activated receptor subtype (PPAR ) has received much attention as the target for antidiabetic drugs, as well as its role in responding to endogenous compounds such as prostaglandin . However, thiazolidinediones (TZDs), the synthetic agonists of the PPAR are tightly associated with fluid retention and edema, as potentially serious side effects. The epithelial sodium channel (ENaC) represents the rate limiting step for sodium absorption in the renal collecting duct. Consequently, ENaC is a central effector impacting systemic blood volume and pressure. The role of PPAR agonists on ENaC activity remains controversial. While PPAR agonists were shown to stimulate ENaC-mediated renal salt absorption, probably via Serum- and Glucocorticoid-Regulated Kinase 1 (SGK1), other studies reported that PPAR agonist-induced fluid retention is independent of ENaC activity. The current paper provides new insights into the control and function of ENaC and ENaC-mediated sodium transport as well as several other epithelial channels/transporters by PPARs and particularly PPAR . The potential contribution of arachidonic acid (AA) metabolites in PPAR-dependent mechanisms is also discussed.