Laboratory of Cell Biology, Institute of Life Science, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
PLoS One. 2010 Sep 9;5(9):e12656. doi: 10.1371/journal.pone.0012656.
A link between early mismatched nutritional environment and development of components of the metabolic syndrome later in life has been shown in epidemiological and animal data. The aim of this study was to investigate whether an early mismatched nutrition produced by catch-up growth after fetal protein restriction could induce the appearance of hypertension and/or atherosclerosis in adult male mice.
METHODOLOGY/PRINCIPAL FINDINGS: Wild-type C57BL6/J or LDLr-/- dams were fed a low protein (LP) or a control (C) diet during gestation. Catch-up growth was induced in LP offspring by feeding dams with a control diet and by culling the litter to 4 pups against 8 in controls. At weaning, male mice were fed either standard chow or an obesogenic diet (OB), leading to 4 experimental groups. Blood pressure (BP) and heart rate (HR) were assessed in conscious unrestrained wild-type mice by telemetry. Atherosclerosis plaque area was measured in aortic root sections of LDLr-/- mice. We found that: (1) postnatal OB diet increased significantly BP (P<0.0001) and HR (P<0.008) in 3-month old OB-C and OB-LP offspring, respectively; (2) that maternal LP diet induced a significant higher BP (P<0.009) and HR (P<0.004) and (3) an altered circadian rhythm in addition to higher plasma corticosterone concentration in 9 months-old LP offspring; (4) that, although LP offspring showed higher plasma total cholesterol than control offspring, atherosclerosis assessed in aortic roots of 6-mo old mice featured increased plaque area due to OB feeding but not due to early mismatched nutrition.
CONCLUSIONS/SIGNIFICANCE: These results indicate a long-term effect of early mismatched nutrition on the appearance of hypertension independently of obesity, while no effect on atherosclerosis was noticed at this age.
流行病学和动物数据表明，早期营养环境不匹配与生命后期代谢综合征成分的发展之间存在关联。本研究旨在探讨胎儿蛋白限制后追赶生长产生的早期不匹配营养是否会诱导成年雄性小鼠出现高血压和/或动脉粥样硬化。
方法/主要发现：野生型 C57BL6/J 或 LDLr-/- 母鼠在妊娠期分别给予低蛋白（LP）或对照（C）饮食。LP 后代的追赶生长通过给予母鼠对照饮食和将 litter 减少到 4 只，而对照组为 8 只来实现。在断奶时，雄性小鼠分别给予标准饮食或致肥胖饮食（OB），导致 4 个实验组。通过遥测术评估清醒、不受约束的野生型小鼠的血压（BP）和心率（HR）。我们发现：（1）OB 饮食使 OB-C 和 OB-LP 后代的 BP（P<0.0001）和 HR（P<0.008）分别显著增加；（2）LP 饮食使 9 个月大的 LP 后代的 BP（P<0.009）和 HR（P<0.004）显著升高，并导致昼夜节律改变，同时血浆皮质酮浓度升高；（3）尽管 LP 后代的血浆总胆固醇水平高于对照组后代，但在 6 个月大的小鼠中评估的动脉粥样硬化斑块面积由于 OB 喂养而增加，但由于早期不匹配的营养而没有增加。
结论/意义：这些结果表明，早期不匹配营养对高血压的出现有长期影响，而与肥胖无关，而在这个年龄，对动脉粥样硬化没有影响。
