Upregulation of growth signaling and nutrient transporters in cotyledons of early to mid-gestational nutrient restricted ewes.

Upregulation of growth signaling and nutrient transporters in cotyledons of early to mid-gestational nutrient restricted ewes.
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DOI:
10.1016/j.placenta.2011.01.007
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发表时间:
2011-03
期刊:
影响因子:
3.8
通讯作者:
Ford, S. P.
Ford, S. P.
中科院分区:
医学3区
文献类型:
--
作者:
Ma, Y.;Zhu, M. J.;Uthlaut, A. B.;Nijland, M. J.;Nathanielsz, P. W.;Hess, B. W.;Ford, S. P.

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从妊娠d28-d 78,经产母羊接受100%(对照,C,n=13)或50%(营养限制,NR,n=14)的NRC饮食要求。在第78天,对5只C和6只NR母羊进行尸检。其余8只C和8只NR母羊从d 78-d135饲喂100% NRC并尸检。在尸检时和每周一次采集母体血液,用于测定葡萄糖、胰岛素和瘦素。在第78天和第135天尸检时采集胎仔血液,用于葡萄糖和脂质测定。评价子叶(COT)组织的蛋白质和mRNA表达[脂肪酸转运蛋白(FATP)1、FATP 4、CD 36、葡萄糖转运蛋白(GLUT)1和GLUT 3],仅mRNA表达[胎盘脂肪酸结合蛋白(FABPpm)和脂蛋白脂肪酶(LPL)],或磷酸化和总蛋白形式的表达[AMP激酶(AMPK)α、乙酰辅酶A羧化酶(ACC)、细胞外信号调节激酶(Erk)1/2、哺乳动物雷帕霉素靶蛋白(mTOR)和蛋白激酶B(Akt)]。在第78天,NR组与C组相比,胎盘和胎儿重量降低(P < 0.05),但在第135天未降低(P < 0.05)。与C母羊相比,NR母羊母体循环葡萄糖、胰岛素和瘦素水平在第78天降低(P < 0.05),但在第135天相似。在第78天,NR组的胎儿血糖和甘油三酯水平低于C组(P < 0.05),但在第135天相似。在第78天时,NR组COT中GLUT 1、FATP 4、CD 36 mRNA和蛋白表达水平、FABPpm mRNA水平和Leptin蛋白水平均显著高于C组(P < 0.05)。AMPK、ACC和Erk 1/2活性在第78天也在NR组比C COT组升高(P < 0.05)。与此相反,在第135天时,NR组COT中只有FATP 4的mRNA和蛋白水平均显著高于C组(P < 0.05)。这些数据表明胎盘通过增加营养转运蛋白的产生和生长信号传导活性来适应母体NR。
Multiparous ewes received 100% (control, C, n=13) or 50% (nutrient restricted, NR, n=14) of NRC dietary requirements from d28-d78 of gestation. On d78, 5 C and 6 NR ewes were necropsied. The remaining 8 C and 8 NR ewes were fed to 100% of NRC from d78-d135 and necropsied. Maternal blood was collected at both necropsies and at weekly intervals for assay of glucose, insulin and leptin. Fetal blood was collected at d78 and d135 necropsies for assay of glucose and lipids. Cotyledonary (COT) tissue was evaluated for protein and mRNA expression [fatty acid transporter (FATP)1, FATP4, CD36, glucose transporter (GLUT)1 and GLUT3], mRNA expression only [placenta fatty acid binding protein (FABPpm) and lipoprotein lipase (LPL)], or expression of phosphorylated and total protein forms [AMP kinase (AMPK)α, acetyl-CoA carboxylase (ACC), extracellular signal-regulated kinase (Erk)1/2, mammalian target of rapamycin (mTOR) and protein kinase B (Akt)]. On d78, but not d135, placental and fetal weights were reduced (P < 0.05) in NR vs. C ewes. Maternal circulating glucose, insulin and leptin levels were decreased in NR vs. C ewes on d78 (P < 0.05) but similar at d135. Fetal blood glucose and triglyceride levels were lower in NR vs. C ewes (P < 0.05) on d78, but similar on d135. On d78, GLUT1, FATP4, CD36 mRNA and protein expression levels, FABPpm mRNA level, and leptin protein level were all increased (P < 0.05) in COT of NR vs. C ewes. AMPK, ACC, and Erk1/2 activities were also increased (P < 0.05) in NR vs. C COT on d78. In contrast, only FATP4 was increased (P < 0.05) at both the mRNA and protein levels in COT of NR realimented vs. C ewes on d135. These data demonstrate placental adaptation to maternal NR through increasing nutrient transporter production and growth signaling activity.
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发表时间: 2001-11-02
期刊: SCIENCE
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作者:
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