Maintenance of Kidney Metabolic Homeostasis by PPAR Gamma

Abstract

Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear hormone receptors that control the transcription of specific genes by binding to regulatory DNA sequences. Among the three subtypes of PPARs, PPARγ modulates a broad range of physiopathological processes, including lipid metabolism, insulin sensitization, cellular differentiation, and cancer. Although predominantly expressed in adipose tissue, PPARγ expression is also found in different regions of the kidney and, upon activation, can redirect metabolism. Recent studies have highlighted important roles for PPARγ in kidney metabolism, such as lipid and glucose metabolism and renal mineral control. PPARγ is also implicated in the renin-angiotensin-aldosterone system and, consequently, in the control of systemic blood pressure. Accordingly, synthetic agonists of PPARγ have reno-protective effects both in diabetic and nondiabetic patients. This review focuses on the role of PPARγ in renal metabolism as a likely key factor in the maintenance of systemic homeostasis.

Keywords: PPARγ; RAAS; kidney; lipid; metabolism; nuclear receptors.

Figure 1

PPARγ expression in the kidney and implications for metabolism. PPARγ is expressed in different areas of kidney including the cortex and the medulla, which have different metabolic specializations. Glucose metabolism (blue); Lipid metabolism (purple); Mineral metabolism (green); Blood pressure control (red).

Figure 2

Effects of PPARγ activation in different systems: In the vascular system, PPARγ decreases arterial pressure, relaxes muscular tone, and downregulates RAAS; in adipose tissue, the activation of PPARγ promotes adipogenesis; in β-cells it increases insulin secretion; PPARγ is also anti-inflammatory and from the bone resorption is produced accompanied of release of calcium and phosphate that form stones in the bladder. ANG-II: Angiotensin II; RAAS, Renin Angiotensin Aldosterone System; TGF-β1, transforming growth factor beta 1.