Low leptin gene expression and hyperleptinemia in chronic renal failure

Area of Science:

• Endocrinology
• Nephrology
• Molecular Biology

Background:

• Leptin (ob gene product) regulates appetite and body weight.
• Patients with chronic renal failure (CRF) exhibit elevated serum leptin levels.
• The causes of increased leptin in CRF, whether reduced clearance or increased production, remain unclear.

Purpose of the Study:

• To investigate the relationship between serum leptin levels and kidney function (GFR) in CRF patients.
• To examine ob gene expression in relation to leptin levels, inflammation (CRP), and body composition in advanced CRF.
• To assess changes in leptin and ob gene expression following peritoneal dialysis (PD) treatment.

Main Methods:

• Measured serum leptin and GFR in 219 CRF patients.
• Determined serum leptin, CRP, body composition, and ob gene expression in 15 advanced CRF patients.
• Re-evaluated 7 patients after 12 months of PD treatment.

Main Results:

• Serum leptin levels negatively correlated with GFR (r = -0.26; P < 0.0001).
• Ob gene expression was lower in CRF patients than controls and negatively correlated with leptin in low-CRP patients.
• Ob gene expression was higher in patients with high CRP (> 25 mg/liter) and increased significantly with inflammation.

Conclusions:

• Elevated leptin in CRF is primarily due to decreased plasma clearance, leading to down-regulation of ob gene expression.
• Inflammation (elevated CRP) stimulates ob gene expression, potentially overcoming leptin-induced feedback inhibition.
• Peritoneal dialysis increased body fat but did not alter ob gene expression over 12 months.