Acute leptin exposure reduces megalin expression and upregulates TGFβ1 in cultured renal proximal tubule cells

Increased leptin concentrations observed in obesity can lead to proteinuria, suggesting that leptin may play a role in obesity-related kidney disease. Obesity reduces activation of AMP-activated protein kinase (AMPK) and increases transforming growth factor-beta 1 (TGF-beta 1) expression in the kidney, leading to albuminuria. Thus we investigated if elevated leptin altered AMPK and TGF-beta 1 signaling in proximal tubule cells (PTCs). In opossum kidney (OK) PTCs Western blot analysis demonstrated that leptin upregulates TGF-beta 1 secretion (0.50 mu g/ml) and phosphorylated AMPK alpha (at 0.25, and 0.50 mu g/ml), and downregulates megalin expression at all concentrations (0.05-0.50 mu g/ml). Using the AMPK inhibitor, Compound C, leptin exposure regulated TGF-beta 1 expression and secretion in PTCs via an AMPK mediated pathway. In addition, elevated leptin exposure (0.50 mu g/ml) reduced albumin handling in OK cells independently of megalin expression. This study demonstrates that leptin upregulates TGF-beta 1, reduces megalin, and reduces albumin handling in PTCs by an AMPK mediated pathway. (C) 2014 Elsevier Ireland Ltd. All rights reserved.