A calcium-deficient diet in rat dams during gestation and nursing affects hepatic 11β-hydroxysteroid dehydrogenase-1 expression in the offspring.

A calcium-deficient diet in rat dams during gestation and nursing affects hepatic 11β-hydroxysteroid dehydrogenase-1 expression in the offspring.
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DOI:
10.1371/journal.pone.0084125
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Kaneko K
Kaneko K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Takaya J;Yamanouchi S;Kaneko K

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产前营养不良可以通过改变特定基因的表观遗传调控来影响后代的表型。一些证据表明,钙(Ca)在胰岛素抵抗综合征的发病机制中起重要作用。我们假设,喂食缺钙饮食的怀孕雌性大鼠的后代肝脏糖皮质激素相关基因表达会发生改变,而哺乳会改变这些改变。我们测定了妊娠期和/或哺乳期钙缺乏对后代肝脏11β-羟基类固醇脱氢酶-1 (Hsd11b1)表达的影响。雌性Wistar大鼠从孕前3周至产后21天随意食用缺钙(D: 0.008% Ca)或对照(C: 0.90% Ca)饮食。在出生后第1天,将幼崽交叉饲养于相同或相反的母鼠中,分为CC、DD、CD和DC 4组(首字母:原母鼠日粮,第二字母:哺乳期母鼠日粮)。从断奶(第21天)开始饲喂对照饲粮,于第200±7天处死。采用ELISA试剂盒检测子代血清胰岛素和脂肪因子。在男性中,DD和DC组的胰岛素、葡萄糖和胰岛素抵抗稳态模型评估(HOMA-IR)的平均水平高于CC组。我们发现无论是男性还是女性,CC组和CD组之间的HOMA-IR没有差异。Hsd11b1在雄性DD大鼠中的表达低于CC大鼠。交叉饲养的雄性后代Hsd11b1表达量高于相同饲粮喂养的雄性后代;CC vs CD, DD vs DC。雌性DC大鼠Hsd11b1表达高于CC大鼠。这些发现表明,孕妇在怀孕和/或哺乳期限制钙会以性别特异性的方式改变产后生长、Hsd11b1表达和胰岛素抵抗。
Prenatal malnutrition can affect the phenotype of offspring by changing epigenetic regulation of specific genes. Several lines of evidence demonstrate that calcium (Ca) plays an important role in the pathogenesis of insulin resistance syndrome. We hypothesized that pregnant female rats fed a Ca-deficient diet would have offspring with altered hepatic glucocorticoid-related gene expression and that lactation would modify these alterations. We determined the effects of Ca deficiency during pregnancy and/or lactation on hepatic 11β-hydroxysteroid dehydrogenase-1 (Hsd11b1) expression in offspring. Female Wistar rats consumed either a Ca-deficient (D: 0.008% Ca) or control (C: 0.90% Ca) diet ad libitum from 3 weeks preconception to 21 days postparturition. On postnatal day 1, pups were cross-fostered to the same or opposite dams and divided into the following four groups: CC, DD, CD, and DC (first letter: original mother's diet; second letter: nursing mother's diet). All offspring were fed a control diet beginning at weaning (day 21) and were killed on day 200±7. Serum insulin and adipokines in offspring were measured using ELISA kits. In males, mean levels of insulin, glucose, and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) were higher in the DD and DC groups than in the CC group. We found no difference in HOMA-IR between the CC and CD groups in either males or females. Expression of Hsd11b1 was lower in male DD rats than in CC rats. Hsd11b1 expression in male offspring nursed by cross-fostered dams was higher than that in those nursed by dams fed the same diet; CC vs. CD and DD vs. DC. In females, Hsd11b1 expression in DC rats was higher than that in CC rats. These findings indicated that maternal Ca restriction during pregnancy and/or lactation alters postnatal growth, Hsd11b1 expression, and insulin resistance in a sex-specific manner.
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