Leptin and renal fibrosis.

Area of Science:

• Nephrology
• Endocrinology
• Molecular Biology

Background:

• Leptin, a key regulator of energy balance, influences various physiological processes.
• Emerging evidence suggests leptin's role in renal pathophysiology, potentially linking obesity and diabetes to kidney disease.
• The kidney's interaction with leptin, including its metabolism and receptor expression, is not fully understood.

Purpose of the Study:

• To investigate the direct and indirect effects of leptin on kidney cells and function.
• To explore leptin's potential contribution to obesity-associated kidney disease and diabetic nephropathy.
• To elucidate the signaling pathways involved in leptin-induced renal changes.

Main Methods:

• In vitro studies using cultured rat renal endothelial and mesangial cells.
• Experiments with db/db mice and normal rats infused with leptin.
• Analysis of gene expression (collagen type IV, fibronectin) in transgenic mice.
• Measurement of cellular responses like proliferation, hypertrophy, glucose transport, and protein synthesis.

Main Results:

• Leptin stimulated proliferation of glomerular endothelial cells and increased TGF-beta1 and collagen type IV production.
• In mesangial cells, leptin enhanced glucose transport, collagen type I synthesis, and hypertrophy, involving phosphatidylinositol-3-kinase signaling.
• Leptin infusion in rats induced glomerulosclerosis and proteinuria.
• Overexpression of leptin in mice led to increased renal collagen type IV and fibronectin mRNA.

Conclusions:

• The kidney is a target organ for leptin.
• Leptin plays a significant role in renal pathophysiology, potentially contributing to kidney disease in obesity and type 2 diabetes.
• Leptin's effects on renal cells involve specific signaling pathways and receptor isoforms (Ob-Ra).