LOW LEPTIN GENE-EXPRESSION AND HYPERLEPTINEMIA IN CHRONIC-RENAL-FAILURE

Citation
L. Nordfors et al., LOW LEPTIN GENE-EXPRESSION AND HYPERLEPTINEMIA IN CHRONIC-RENAL-FAILURE, Kidney international, 54(4), 1998, pp. 1267-1275
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Urology & Nephrology
Journal title
ISSN journal
0085-2538
Volume
54
Issue
4
Year of publication
1998
Pages
1267 - 1275
Database
ISI
SICI code
0085-2538(1998)54:4<1267:LLGAHI>2.0.ZU;2-G
Abstract
Background. The ob gene product leptin is thought to be a key regulato r of food intake and body weight. Patients having advanced chronic ren al failure (CRF) have markedly higher serum leptin levels. It is not k nown whether the increase in leptin levels in CRF is caused by a decre ased plasma clearance and/or increased production. Methods. In the pre sent study serum leptin levels and glomerular filtration rate (GFR) we re measured in 219 patients having various degrees of renal failure. I n addition, serum leptin levels, C-reactive protein (CRP), body compos ition (by dual-energy x-ray absorptiometry) and ob gene expression (by in situ hybridization histochemistry) were determined in 15 patients with advanced CRF. Seven of the patients were re-evaluated following 1 2 months of peritoneal dialysis (PD) treatment. Results. Serum leptin levels correlated negatively to GFR (r = -0.26; P < 0.0001). The ob ge ne expression was significantly lower in patients with CRF than in hea lthy controls. A negative correlation between serum leptin levels and ob gene expression (r = -0.66; P < 0.05) was found in patients with CR P < 25 mg/liter. The ob gene expression (20.0 +/- 1.8 vs. 15.0 +/- 1.0 nCi/g; P < 0.05) was significantly higher in 5 patients with CRP > 25 mg/liter than in 10 patients with CRP < 25 mg/liter. Following 12 mon ths of PD, the amount of body fat increased by 30% while the ob gene e xpression remained unchanged. Conclusion. The present study shows a co rrelation between serum leptin levels and GFR, and our results suggest that elevated leptin levels, due to a decreased plasma clearance, dow n-regulate the expression of the ob gene. We also found that an ongoin g inflammation stimulates ob gene expression in patients with CRF. The refore, it is suggested that the hyperleptinemia induced feedback inhi bition of ob gene expression is overcome by inflammatory cytokines.