Harborne Building 12A, School of Biological Sciences, University of Reading, Whiteknights, Reading, Berkshire RG6 6AS, UK.
Institute of Developmental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital (MP887), Tremona Road, Southampton SO16 6YD, UK.
Nutrients. 2018 Nov 28;10(12):1832. doi: 10.3390/nu10121832.
Obesity is a growing health crisis of pandemic proportions. Numerous animal and human studies have confirmed that obesity and related metabolic abnormalities, such as insulin resistance and cardiovascular disease, may be programmed during development by adverse maternal nutrition. We previously documented that offspring of female mice who were protein-restricted during pregnancy alone had no alterations to their body weights, but did display a considerable reduction in food intake, a finding which was linked to reduced expression levels of appetite regulatory genes in the hypothalamus. Whether such observations were accompanied by changes in metabolic and phenotypic parameters remained to be determined. Female pregnant MF-1 mice were fed, exclusively during the pregnancy period, a normal protein diet containing 18% casein (C) or an isocaloric protein-restricted diet containing 9% casein (PR). From birth, the lactating dams were fed a normal protein diet. At weaning, offspring were fed either the standard chow which contain 7% kcal fat (C) or high-fat diet (HF, 45% kcal fat). This yielded 4 experimental groups denoted by maternal diet/offspring diet: C/C, C/HF, PR/C, PR/HF. Our results showed that offspring adiposity was significantly increased in HF-fed offspring, and was not affected by the 50% reduction in protein content of the maternal diet fed during pregnancy. Similarly, blood glucose levels were higher in HF-fed offspring, regardless of protein content of the maternal diet. Systolic blood pressure, on the other hand, was significantly increased in both male and female offspring of dams fed the PR diet, and this was exacerbated by a postweaning HF diet. Our results show that maternal protein restriction leads to elevations in systolic blood pressure, which is exacerbated by a postweaning HF-diet. Our present findings suggest that, while changes in offspring adiposity brought about by exposure to maternal protein restriction during pregnancy may be restored by adequate maternal protein content during lactation, the same may not be true for systolic blood pressure, which was similarly impaired, regardless of the timing of maternal low-protein exposure.
肥胖是一种日益严重的健康危机，其规模堪比大流行。大量动物和人类研究已经证实，肥胖和相关代谢异常，如胰岛素抵抗和心血管疾病，可能在发育过程中因母体营养不良而受到编程影响。我们之前的研究表明，仅在怀孕期间限制蛋白质摄入的雌性小鼠的后代体重没有变化，但它们的食物摄入量明显减少，这一发现与下丘脑食欲调节基因的表达水平降低有关。这种观察结果是否伴随着代谢和表型参数的变化仍有待确定。怀孕的 MF-1 雌性小鼠在怀孕期间仅喂食正常蛋白质饮食（含 18%乳清蛋白）或等热量蛋白质限制饮食（含 9%乳清蛋白）。从出生起，哺乳期的母鼠就喂食正常蛋白质饮食。在断奶时，后代喂食标准食物（含 7%卡路里脂肪）或高脂肪饮食（含 45%卡路里脂肪）。这产生了 4 个实验组，分别由母鼠饮食/后代饮食表示：C/C、C/HF、PR/C、PR/HF。我们的研究结果表明，高脂肪饮食会显著增加后代的肥胖程度，而母鼠怀孕期间饮食蛋白质含量减少 50%并不会影响这一结果。同样，无论母鼠饮食中的蛋白质含量如何，高脂肪饮食都会导致后代的血糖水平升高。另一方面，母鼠喂食 PR 饮食会导致雄性和雌性后代的收缩压显著升高，而这种情况在断奶后喂食高脂肪饮食时会加剧。我们的研究结果表明，母鼠蛋白质限制会导致收缩压升高，而断奶后高脂肪饮食会加剧这种情况。我们目前的研究结果表明，尽管怀孕期间暴露于母体蛋白质限制会导致后代肥胖程度的变化，但通过哺乳期提供充足的母体蛋白质含量可能会恢复这些变化，但对于收缩压而言，情况可能并非如此，因为无论母体低蛋白暴露的时间如何，收缩压都会受到类似的损害。
