Catch-up growth following intra-uterine growth-restriction programmes an insulin-resistant phenotype in adipose tissue.
Catch-up growth following intra-uterine growth-restriction programmes an insulin-resistant phenotype in adipose tissue.
复制标题
在脂肪组织中胰岛素耐药的表型后，捕获胰岛素抗性的表型后，追赶生长。
DOI：
10.1038/ijo.2012.196
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发表时间：
2013-08
影响因子：
4.9
通讯作者：
Ozanne, S. E.
中科院分区：
文献类型：
--
作者：
Berends, L. M.;Fernandez-Twinn, D. S.;Martin-Gronert, M. S.;Cripps, R. L.;Ozanne, S. E.
关键词：
现在人们普遍认为，生命早期的营养环境在决定对代谢性疾病的易感性方面是重要的。特别是，宫内生长受限后出生后生长加速与肥胖、2型糖尿病和代谢综合征其他特征的风险增加有关。这些现象背后的机制尚未完全了解。使用一个成熟的母体蛋白质限制啮齿动物模型，我们的目的是确定暴露于不匹配的营养在早期生活计划脂肪组织的结构和功能，以及胰岛素信号通路的关键成分的表达。在妊娠期间喂食低蛋白（8%）饲料的母鼠的后代由对照（20%）喂食的母鼠哺乳，以驱动追赶生长。这个“恢复”组与在怀孕和哺乳期间喂食20%蛋白质饮食的母鼠的后代（对照组）进行比较。采用组织学分析研究了22天和3月龄对照组和恢复期雄性大鼠的附睾脂肪组织。胰岛素信号蛋白和基因表达的表达和磷酸化分别通过蛋白质印迹法和逆转录酶PCR进行评估。两个年龄段的恢复后代具有较大的脂肪细胞（P<0.001）。空腹血糖、胰岛素和瘦素水平在两组之间相当，但随着年龄的增长而增加。恢复组仔鼠脂肪组织中IRS-1和PI 3 K p110β的表达明显降低（P<0.01和P<0.001）。在成年恢复期，Akt磷酸化水平（P<0.01）和Akt-2蛋白水平（P<0.01）也降低。这些蛋白质的信使RNA表达水平没有差异，表明转录后效应。生命早期的营养方案改变脂肪细胞的大小，并通过转录后机制损害几种胰岛素信号蛋白的蛋白质表达。这些指标可能代表胰岛素抵抗和代谢疾病风险的早期标志物。
It is now widely accepted that the early-life nutritional environment is important in determining susceptibility to metabolic diseases. In particular, intra-uterine growth restriction followed by accelerated postnatal growth is associated with an increased risk of obesity, type-2 diabetes and other features of the metabolic syndrome. The mechanisms underlying these observations are not fully understood. Using a well-established maternal protein-restriction rodent model, our aim was to determine if exposure to mismatched nutrition in early-life programmes adipose tissue structure and function, and expression of key components of the insulin-signalling pathway. Offspring of dams fed a low-protein (8%) diet during pregnancy were suckled by control (20%)-fed dams to drive catch-up growth. This ‘recuperated' group was compared with offspring of dams fed a 20% protein diet during pregnancy and lactation (control group). Epididymal adipose tissue from 22-day and 3-month-old control and recuperated male rats was studied using histological analysis. Expression and phosphorylation of insulin-signalling proteins and gene expression were assessed by western blotting and reverse-transcriptase PCR, respectively. Recuperated offspring at both ages had larger adipocytes (P<0.001). Fasting serum glucose, insulin and leptin levels were comparable between groups but increased with age. Recuperated offspring had reduced expression of IRS-1 (P<0.01) and PI3K p110β (P<0.001) in adipose tissue. In adult recuperated rats, Akt phosphorylation (P<0.01) and protein levels of Akt-2 (P<0.01) were also reduced. Messenger RNA expression levels of these proteins were not different, indicating a post-transcriptional effect. Early-life nutrition programmes alterations in adipocyte cell size and impairs the protein expression of several insulin-signalling proteins through post-transcriptional mechanisms. These indices may represent early markers of insulin resistance and metabolic disease risk.
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影响因子：
12.4
作者：
通讯作者：
--
影响因子：
6.9
作者：
Bol, Vanesa V.;Reusens, Brigitte M.;Remacle, Claude A.
通讯作者：
Remacle, Claude A.
影响因子：
7
作者：
Dunger, D. B.;Salgin, B.;Ong, K. K.
通讯作者：
Ong, K. K.
影响因子：
6.3
作者：
LAW, CM;BARKER, DJP;SIMMONDS, SJ
通讯作者：
SIMMONDS, SJ
DOI：
10.1152/ajpregu.90497.2008
发表时间：
2009-08-01
影响因子：
2.8
作者：
Bol, V. V.;Delattre, A-I.;Remacle, C.
通讯作者：
Remacle, C.