Upregulation of hepatic 11β-hydroxysteroid dehydrogenase-1 expression in calcium-deficient rats
Upregulation of hepatic 11β-hydroxysteroid dehydrogenase-1 expression in calcium-deficient rats
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缺钙大鼠肝脏 11β-羟基类固醇脱氢酶 1 表达上调
DOI：
10.1159/000332915
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发表时间：
2011
期刊：
影响因子：
3.9
通讯作者：
Kaneko K
中科院分区：
文献类型：
--
作者：
Takaya J;Iharada A;Okihana H;Kaneko K
背景：许多流行病学研究报道了钙（Ca）缺乏和代谢综合征之间的联系。在这项研究中，我们研究钙缺乏症大鼠和糖皮质激素代谢的变化是否induced.Methods：10周龄雌性Wistar大鼠断奶到一个非常低的钙饮食（低钙组）或对照饮食（对照组）2周。采用定量实时PCR评估肝脏中11β-羟基类固醇脱氢酶-1（11β-HSD 1）、11β-HSD 2、磷酸烯醇丙酮酸羧激酶、过氧化物酶体增殖物激活受体-α和糖皮质激素受体的mRNA。脂联素，瘦素，皮质酮，全段甲状旁腺激素，不对称二甲基精氨酸和胰岛素的浓度测定空腹血清中使用大鼠特异性酶联免疫吸附试验。使用葡萄糖氧化酶系统测量葡萄糖浓度。用自动离子选择性电极分析仪测定血清离子钙水平。血清亚硝酸盐/硝酸盐水平测定使用比色测定试剂盒。结果：2周后，观察血清葡萄糖，皮质酮或胰岛素水平没有差异。低钙组大鼠体内稳态模型评估胰岛素抵抗较高，脂联素水平较低，全段甲状旁腺激素水平较高。血清亚硝酸盐/硝酸盐和不对称二甲基精氨酸显着高于低钙组比对照组。低钙组肝脏11β-HSD 1 mRNA表达上调，磷酸烯醇式丙酮酸羧激酶表达下调。结论：低钙饮食改变糖皮质激素代谢，导致肝脏11 β-HSD 1表达上调，可能是钙缺乏代谢并发症的重要机制。
Background:Many epidemiologic studies have reported a link between calcium (Ca) deficiency and metabolic syndrome. In this study, we examine Ca deficiency in rats and whether changes in glucocorticoid metabolism are induced.Methods:Twelve-week-old female Wistar rats were weaned onto a very-low-Ca diet (low-Ca group) or a control diet (control group) for 2 weeks. Quantitative real-time PCR was used to assess mRNA for 11β-hydroxysteroid dehydrogenase-1 (11β-HSD1), 11β-HSD2, phosphoenolpyruvate carboxykinase, peroxisome proliferator-activated receptor-α, and glucocorticoid receptor in the liver. Concentrations of adiponectin, leptin, corticosterone, intact parathyroid hormone, asymmetrical dimethylarginine and insulin in fasting serum were determined using a rat-specific enzyme-linked immunosorbent assay. Glucose concentrations were measured using a glucose oxidase system. Serum ionized Ca levels were measured with an automatic ion-selective electrode analyzer. Serum nitrite/nitrate levels were measured using a colorimetric assay kit.Results:After 2 weeks, no differences in serum glucose, corticosterone or insulin levels were observed. The low-Ca group rats showed higher homeostasis model assessment insulin resistance, lower adiponectin and higher intact parathyroid hormone levels. Serum nitrite/nitrate and asymmetrical dimethylarginine were significantly higher in the low-Ca group than in the control group. The expression of hepatic 11β-HSD1 mRNA was upregulated, while hepatic phosphoenolpyruvate carboxykinase expression was downregulated in the low-Ca group. Glucocorticoid receptor, peroxisome proliferator-activated receptor-α and 11β-HSD2 expression levels showed a similar tendency.Conclusion:A low-Ca diet alters glucocorticoid metabolism, which leads to hepatic upregulation of 11β-HSD1, and is possibly a key mechanism inducing the metabolic complications of Ca deficiency.