The effect of leptin on Na+-H+ antiport (NHE 1) activity of obese and normal subjects erythrocytes

Obesity is currently considered as a chronic metabolic disease. associated with a high risk of cardiovascular complications. Leptin, an adipocyte-deri ved hormone has a variety target cells influencing a wide range of processe s. Possible counteractions of hyperleptinaemia are currently investigated. The Na+-H+ exchanger (NHE 1) is involved in multiple cellular functions and its activation has been related to hypertension and obesity. NHE 1 is pres ent on erythrocytes and can be stimulated by various hormones. Erythrocytes have on their surface a variety of receptors with mostly unknown function. In the present paper, the effect of leptin on erythrocytes NHE 1 activity has been investigated. For this reason, the intracellular pH and sodium inf luxes were measured before and after addition of leptin in erythrocyte susp ensions from normal and obese individuals. Amiloride, a specific NHE 1 inhi bitor. and staurosporine a protein kinase C inhibitor were used to inhibit erythrocyte NHE 1. For the binding study leptin was labeled with fluorescei n isothiocyanate (FITC) and the binding on erythrocytes was estimated by Sc atchard analysis. NHE 1 activity increased in the presence of leptin but si gnificantly less in the obese than in the control group. Furthermore the co ncentrations of leptin binding sites on the surface of erythrocytes were lo wer in erythrocytes drawn from obese individuals than in erythrocytes drawn from normal subjects. Since NHE 1 activity has been associated with insuli n resistance and hypertension, the activation of this antiport by leptin ma y represent a link between adipose tissue hypertrophy and cardiovascular co mplications of obesity. (C) 2001 Elsevier Science Ireland Ltd. All rights r eserved.