Abstract
Involvement of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) in kidney physiology has been explored recently. Synthetic PPARγ ligands can ameliorate the diabetic kidney disease through different mechanisms, involving inhibition of mesangial cell growth, reduction of mesangial matrix, and cytokine production of glomerular cells as well as promoting endothelial cell survival within the kidney glomeruli. Activation of PPARγ has additional profibrotic consequences, which can contribute to wound healing in diabetic glomerulonephritis. Beside many beneficial effects, PPARγ activation, however, can lead to severe water retention, a common side effect of thiazolidinedione therapy. This unwanted effect is due to the activation of PPARγ in the mesonephric distal collecting system, where PPARγ positively regulates sodium and water resorbtion leading to the expansion of interstitial fluid volume. Recent studies indicate that PPARγ is also involved in the normal kidney development, renal lipid metabolism, and activation of the renin-angiotensin system. In this paper, we give a synopsis of the current knowledge on PPARγ functions in kidney phyisology and pathophysiology.
Highlights
The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) regulates transcription of various genes involved in lipid uptake, fatty acid metabolism, and glucose homeostasis [1], the modulation of PPARγ action is of intense interests in the medication of insulin resistance and related metabolic disorders [2,3,4,5,6,7]
PPARγ signaling can influence the expression of insulin-dependent glucose transport (GLUT) proteins [8], and can induce the production of hormone-like substances in adipose cells promoting insulin responsiveness [1]
PPARγ agonists have many beneficial effects combined with their independent antiatherosclerotic actions and their important effects on dyslipidemia and insulin resistance in the medication of kidney disease coupled to diabetes [10, 12,13,14,15, 21, 82]
Summary
The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) regulates transcription of various genes involved in lipid uptake, fatty acid metabolism, and glucose homeostasis [1], the modulation of PPARγ action is of intense interests in the medication of insulin resistance and related metabolic disorders [2,3,4,5,6,7]. Activation of PPARγ in macrophages has anti-inflammatory effects, by which PPARγ ligands can reduce the local low-grade inflammation and consequent insulin resistance of muscle and adipose tissues [5, 6]. Several fundamental findings on the involvement of PPARγ in fluid homeostasis have been explored in the recent years [1, 10,11,12,13,14,15,16,17,18] These findings indicate that PPARγ is involved in the regulation of sodium and water resorbtion of the distal collecting ducts of the kidney which explains the unwanted TZD effects on interstitial fluid volume regulation [9, 17, 18]. PPAR Research as well as the PPARγ-independent effects of synthetic PPARγ ligands in kidney phyisology and pathophysiology
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