Sex differences in renal and metabolic responses to a high-fructose diet in mice.
Sex differences in renal and metabolic responses to a high-fructose diet in mice.
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DOI：
10.1152/ajprenal.00403.2014
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发表时间：
2015-03
期刊：
影响因子：
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通讯作者：
Nikhil Sharma;Lijun Li;C. Ecelbarger
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文献类型：
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作者：
Nikhil Sharma;Lijun Li;C. Ecelbarger
高果糖摄入量与肾脏疾病和高血压等疾病的发病率增加有关。大多数果糖被门静脉系统清除并在肝脏中代谢;然而，果糖的全身水平会随着消耗量的增加而升高。我们测试了小鼠对高果糖饮食的肾脏反应是否存在性别差异。将两个月大的雄性和雌性C57 BL 6/129/SV小鼠（n = 6只小鼠/性别/处理）随机接受对照或高果糖（65%重量）饮食作为颗粒状食物，自由采食3个月。果糖喂养没有显著影响体重，但导致雄性和雌性小鼠的肾脏重量分别增加19%和10%。在雄性小鼠中，果糖增加了参与代谢的肾皮质蛋白的表达（约50%），包括葡萄糖转运蛋白5（促进性果糖转运蛋白）、酮己糖激酶和胰岛素受体（β亚基）。雌性小鼠葡萄糖转运蛋白5的基础水平较低，对果糖无反应。然而，雌性小鼠的尿量和血浆K（+）增加，血浆Na（+）降低，而雄性小鼠的影响较小。同样，与雌性对照组小鼠相比，雌性小鼠的粗升支中Na（+）-K（+）-2Cl（-）协同转运蛋白2和集合管中水通道蛋白2的表达与果糖相比降低了2 - 3倍，而雄性小鼠没有变化。总的来说，我们的研究结果支持更大的近端代谢的果糖在雄性动物和更大的远端小管/集合管（电解质稳态）的改变在雌性动物。这些性别差异可能是与高果糖消耗相关的病理学的特定性质的重要决定因素。
High fructose intake has been associated with increased incidences of renal disease and hypertension, among other pathologies. Most fructose is cleared by the portal system and metabolized in the liver; however, systemic levels of fructose can rise with increased consumption. We tested whether there were sex differences in the renal responses to a high-fructose diet in mice. Two-month-old male and female C57BL6/129/SV mice (n = 6 mice per sex per treatment) were randomized to receive control or high-fructose (65% by weight) diets as pelleted chow ad libitum for 3 mo. Fructose feeding did not significantly affect body weight but led to a 19% and 10% increase in kidney weight in male and female mice, respectively. In male mice, fructose increased the expression (∼50%) of renal cortical proteins involved in metabolism, including glucose transporter 5 (facilitative fructose transporter), ketohexokinase, and the insulin receptor (β-subunit). Female mice had lower basal levels of glucose transporter 5, which were unresponsive to fructose. However, female mice had increased urine volume and plasma K(+) and decreased plasma Na(+) with fructose, whereas male mice were less affected. Likewise, female mice showed a two- to threefold reduction in the expression Na(+)-K(+)-2Cl(-) cotransporter 2 in the thick ascending limb and aquaporin-2 in the collecting duct with fructose relative to female control mice, whereas male mice had no change. Overall, our results support greater proximal metabolism of fructose in male animals and greater distal tubule/collecting duct (electrolyte homeostasis) alterations in female animals. These sex differences may be important determinants of the specific nature of pathologies that develop in association with high fructose consumption.