Sexual Dimorphism in Cafeteria Diet-Induced Hypertension Is Associated with Gender-Related Difference in Renal Leptin Receptor Down-Regulation

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Abstract
Plasma leptin levels are elevated in obesity suggesting a pathophysiologic role of this hormone in obesity and related disorders, such as hypertension. Furthermore, despite excess leptin levels, leptin satiety action is blunted in obesity suggesting the occurrence of central leptin resistance. As leptin acts on the kidney to induce natriuresis, renal leptin receptor alterations could lead to a defect in sodium excretion and hence to hypertension. Therefore, the present study investigated renal leptin receptor (Ob-Ra and Ob-Rb) mRNA and leptin binding capacities in diet-induced hypertension. Feeding male, female, and testosterone-treated female rats a cafeteria diet for 10 weeks increased body fat mass, plasma insulin, and leptin levels. Furthermore, although male and testosterone-treated female cafeteria-fed rats were hypertensive, the female rats fed the same diet failed to develop elevated blood pressure. In renal medulla, Ob-Ra and Ob-Rb mRNA levels were unchanged after cafeteria diet feeding in all groups; however, binding analysis revealed Ob-R protein down-regulation exclusively in hypertensive rats. Moreover, renal Ob-R densities were inversely correlated to plasma leptin concentrations in male rats and testosterone-treated female rats but not in female rats. These findings demonstrate the existence of differences in renal Ob-R binding capacities, which are correlated to hypertension.