Sexual dimorphism in cafeteria diet-induced hypertension is associated with gender-related difference in renal leptin receptor down-regulation
Sexual dimorphism in cafeteria diet-induced hypertension is associated with gender-related difference in renal leptin receptor down-regulation
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DOI：
10.1124/jpet.102.045682
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发表时间：
2003-04-01
影响因子：
3.5
通讯作者：
Ribière, C
中科院分区：
文献类型：
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作者：
Coatmellec-Taglioni, G;Dausse, JP;Ribière, C
血浆瘦素水平在肥胖症中升高，表明这种激素在肥胖症和相关疾病如高血压中的病理生理作用。此外，尽管过量的瘦素水平，瘦素饱腹感的行动是钝化的肥胖症表明发生中枢瘦素抵抗。由于瘦素作用于肾脏以诱导尿钠排泄，肾脏瘦素受体改变可导致钠排泄缺陷，从而导致高血压。因此，本研究探讨肾瘦素受体（Ob-Ra和Ob-Rb）的mRNA和瘦素结合能力在饮食诱导的高血压。给雄性、雌性和睾酮治疗的雌性大鼠喂食自助餐10周，增加了体脂量、血浆胰岛素和瘦素水平。此外，虽然雄性和睾酮治疗的雌性大鼠高血压，喂养相同的饮食的雌性大鼠没有发展血压升高。在肾髓质，Ob-Ra和Ob-Rb mRNA水平无变化后，自助餐饮食喂养在所有组，然而，结合分析显示Ob-R蛋白下调只在高血压大鼠。此外，肾Ob-R密度呈负相关，血浆瘦素浓度在雄性大鼠和睾酮治疗的雌性大鼠，但在雌性大鼠。这些发现表明存在差异，肾Ob-R结合能力，这是相关的高血压。
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.