Chen Jian-Hua, Martin-Gronert Malgorzata S, Tarry-Adkins Jane, Ozanne Susan E
University of Cambridge Metabolic Research Laboratories Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom.
PLoS One. 2009;4(3):e4950. doi: 10.1371/journal.pone.0004950. Epub 2009 Mar 24.
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 p85alpha (P = 0.018), p110beta (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.
我们之前报道过，啮齿动物母体蛋白质限制会影响其早期生长速率，并最终影响寿命。母体蛋白质限制导致低出生体重，随后出现追赶生长（恢复生长的动物）与寿命缩短有关，而哺乳期蛋白质限制和生长缓慢（产后低蛋白：PLP动物）则会延长寿命。我们旨在探究这些差异产生的机制基础。在此，我们研究了母体饮食对雄性小鼠断奶时器官生长、代谢参数以及肌肉中胰岛素/IGF1信号蛋白和Sirt1表达的影响。在哺乳期经历蛋白质限制的PLP小鼠空腹血糖（P = 0.038）和胰岛素水平（P = 0.046）较低，表明胰岛素敏感性提高。与对照组相比，PLP小鼠大脑（P = 0.0002）和胸腺（P = 0.031）的相对重量（按体重调整）更高，这表明这两个组织功能能力的增强对寿命有益。它们胰岛素受体底物1（P = 0.021）和蛋白激酶C ζ（P = 0.046）的表达也有所增加。恢复生长的动物许多胰岛素信号蛋白的表达水平降低，包括PI3激酶亚基p85α（P = 0.018）、p110β（P = 0.048）和蛋白激酶C ζ（P = 0.006），这可能使这些动物易患胰岛素抵抗。恢复生长的后代中Sirt1蛋白表达降低。这些观察结果表明，母体蛋白质限制可影响年轻时参与寿命调节的主要代谢途径，这可能解释了母体饮食对寿命的影响。
