The dangerous road of catch‐up growth
The dangerous road of catch‐up growth
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DOI：
10.1111/j..2002.00005.x
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发表时间：
2003-02
期刊：
影响因子：
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通讯作者：
C. Hales;S. Ozanne
中科院分区：
文献类型：
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作者：
C. Hales;S. Ozanne
许多流行病学研究现已表明，在新生儿时期表现出早期（胎儿和产后早期）生长不良迹象的成年人中，患2型糖尿病和代谢综合征的风险大大增加。节俭表型假说的提出为这些关系提供了概念和实验可检验的基础。我们已经使用蛋白质限制的大鼠水坝，作为一种手段来检验这一假设。在体内和体外对这类妊娠的生长受限后代的研究已经提供了与人类条件惊人相似的发现。肝脏、肌肉和脂肪组织中调节蛋白表达的永久性变化至少部分解释了所观察到的变化，并为在人类环境中进行测试提供了潜在的标记。这些研究也提出了一个问题，即早期发育迟缓后的“追赶型”发育是否会增加这种早期障碍带来的风险。雄性大鼠在胎儿时期发育迟缓，出生后不久就被交叉培养成正常的泌乳鼠，断奶后体重和器官重量恢复正常，但寿命缩短。这一发现提出了追赶增长的可能性，虽然短期内可能有益，但可能不利于长期生存。人类流行病学研究可能指向同样的方向。其他人对其他早期生长限制模型的研究也得出了类似的数据，尽管数据更有限。这些发现提出了一种有趣的可能性，即对胎儿压力的反应，无论是营养的还是其他的，可能会引起某种程度上限制和统一的适应性反应模式。
Many epidemiological studies have now shown a strongly increased risk of developing type 2 diabetes and the metabolic syndrome in adults who as neonates showed signs of poor early (fetal and early postnatal) growth. The thrifty phenotype hypothesis was proposed to provide a conceptual and experimentally testable basis of these relationships. We have used protein restriction of rat dams, as a means to test this hypothesis. In vivo and in vitro studies of the growth‐restricted offspring of such pregnancies have provided findings showing remarkable parallels with the human conditions. Permanent changes in the expression of regulatory proteins in liver, muscle and adipose tissue provide at least part of the explanation of the changes observed and offer potential markers for testing in the human context. These studies have also raised the question as to whether ‘catch up’ growth following early growth retardation may add to the risks posed by this early handicap. Male rats growth‐retarded during fetal life and cross‐fostered shortly after birth to normal lactating dams reach normal body and organ weights by weaning but have a reduced longevity. This finding raises the possibility that catch up growth, whilst potentially beneficial in the short term, may be detrimental to long‐term survival. Human epidemiological studies may point in the same direction. Work by others on other models of early growth restriction have produced similar, although more limited, data. These findings raise the interesting possibility that the response to fetal stress, be it nutritional or other, may evoke a somewhat restricted and uniform pattern of adaptive response.