Maternal protein restriction affects postnatal growth and the expression of key proteins involved in lifespan regulation in mice.
Maternal protein restriction affects postnatal growth and the expression of key proteins involved in lifespan regulation in mice.
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DOI：
10.1371/journal.pone.0004950
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Ozanne SE
中科院分区：
文献类型：
--
作者：
Chen JH;Martin-Gronert MS;Tarry-Adkins J;Ozanne SE
我们以前曾报道过，啮齿动物的母体蛋白质限制影响了生命早期的生长速度，并最终影响了寿命。由母体蛋白质限制引起的低出生体重，随后追赶生长（恢复的动物）与寿命缩短有关，而蛋白质限制和哺乳期生长缓慢（出生后低蛋白质：PLP动物）增加了寿命。我们的目的是探讨这些差异产生的机制基础。在这里，我们研究了断奶时母体饮食对雄性小鼠器官生长，代谢参数和胰岛素/IGF 1信号蛋白和Sirt 1在肌肉中的表达的影响。在哺乳期间经历蛋白质限制的PLP小鼠具有较低的空腹血糖（P = 0.038）和胰岛素水平（P = 0.046），这表明改善的胰岛素敏感性。 与对照组相比，PLP小鼠的脑（P = 0.0002）和胸腺（P =0.031）的相对重量（经体重调整）更高，表明这两种组织的功能能力增强有利于长寿。 胰岛素受体底物1（P = 0.021）和蛋白激酶C ζ（P = 0.046）的表达也增加。 恢复后的动物表达了许多胰岛素信号蛋白的水平降低，包括PI 3激酶亚基p85α（P = 0.018），p110β（P = 0.048）和蛋白激酶C zeta（P = 0.006），这可能使这些动物易于发生胰岛素抵抗。 Sirt 1蛋白表达在恢复的后代中减少。这些观察结果表明，母体蛋白质限制可以影响在年轻时参与寿命调节的主要代谢途径，这可以解释母体饮食对寿命的影响。
We previously reported that maternal protein restriction in rodents influenced the rate of growth in early life and ultimately affected longevity. Low birth weight caused by maternal protein restriction followed by catch-up growth (recuperated animals) was associated with shortened lifespan whereas protein restriction and slow growth during lactation (postnatal low protein: PLP animals) increased lifespan. We aim to explore the mechanistic basis by which these differences arise. Here we investigated effects of maternal diet on organ growth, metabolic parameters and the expression of insulin/IGF1 signalling proteins and Sirt1 in muscle of male mice at weaning. PLP mice which experienced protein restriction during lactation had lower fasting glucose (P = 0.038) and insulin levels (P = 0.046) suggesting improved insulin sensitivity. PLP mice had higher relative weights (adjusted by body weight) of brain (P = 0.0002) and thymus (P = 0.031) compared to controls suggesting that enhanced functional capacity of these two tissues is beneficial to longevity. They also had increased expression of insulin receptor substrate 1 (P = 0.021) and protein kinase C zeta (P = 0.046). Recuperated animals expressed decreased levels of many insulin signalling proteins including PI3 kinase subunits p85α (P = 0.018), p110β (P = 0.048) and protein kinase C zeta (P = 0.006) which may predispose these animals to insulin resistance. Sirt1 protein expression was reduced in recuperated offspring. These observations suggest that maternal protein restriction can affect major metabolic pathways implicated in regulation of lifespan at a young age which may explain the impact of maternal diet on longevity.
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影响因子：
15.8
作者：
Civitarese AE;Carling S;Heilbronn LK;Hulver MH;Ukropcova B;Deutsch WA;Smith SR;Ravussin E;CALERIE Pennington Team
通讯作者：
CALERIE Pennington Team
影响因子：
--
作者：
Holzenberger, M
通讯作者：
Holzenberger, M
影响因子：
3.9
作者：
Martin-Gronert, M. S.;Ozanne, S. E.
通讯作者：
Ozanne, S. E.
影响因子：
10.5
作者：
Chen, Danica;Bruno, Joanne;Guarente, Leonard
通讯作者：
Guarente, Leonard
影响因子：
7.8
作者：
Katic, Masa;Kennedy, Adam R.;Kahn, C. Ronald
通讯作者：
Kahn, C. Ronald