Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Cook Medical Europe APS, Bjaeverskov, Denmark School of Animal Biology, University of Western Australia, Perth, Western Australia, Australia Department of Basic Sciences and Environment, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Department of Animal Science, Faculty of Science and Technology, Aarhus University, Aarhus, Denmark Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Nuclear Magnetic Resonance Centre, University of Copenhagen, Copenhagen, Denmark.
J Endocrinol. 2013 Oct 4;219(2):159-71. doi: 10.1530/JOE-13-0099. Print 2013 Nov.
Maternal undernutrition increases the risk of type 2 diabetes and metabolic syndrome later in life, particularly upon postnatal exposure to a high-energy diet. However, dysfunctions of, for example, the glucose-insulin axis are not readily detectable by conventional tests early in life, making it difficult to identify individuals at risk. Thus, other methods are required. We hypothesised that prenatally undernourished individuals (but not postnatally overnourished ones) are adapted to a life with limited food availability, which would be evident under conditions reflecting starvation, stress and short-term abundance of food. In this study, twin-pregnant sheep were fed diets meeting 100% (NORM) or 50% (LOW) of energy and protein requirements during the last trimester. Twin offspring were fed either a normal moderate (CONV) diet or a high-carbohydrate-high-fat (HCHF) diet from 3 days to 6 months of age (approximately puberty) and the same moderate diet thereafter until 2 years of age (young adulthood; only females), resulting in four groups: NORM-CONV, LOW-CONV, NORM-HCHF and LOW-HCHF. At the age of 6 months and 2 years respectively, they were subjected to fasting and propionate (nutrient abundance) and adrenalin challenges. At 6 months of age, postnatal HCHF diet exposure caused metabolic alterations, reflecting hypertriglyceridaemia and altered pancreatic β-cell secretion. Irrespective of postnatal diet, prenatal undernutrition was found to be associated with unexpected endocrine responses of leptin, IGF1 and cortisol during fasting (lack of or the opposite response compared with the controls) in 2-year-old adults. In conclusion, a HCHF diet interfered with β-cell function, whereas maternal undernutrition did not lead to any changes in the LOW offspring, except to abnormal hormone responses, suggesting that fetal programming interferes with hypothalamic integration of important endocrine axis.
母体营养不良会增加个体在生命后期患 2 型糖尿病和代谢综合征的风险，尤其是在产后接触高能量饮食后。然而，例如葡萄糖-胰岛素轴的功能障碍在生命早期通过常规测试不易察觉，这使得识别处于风险中的个体变得困难。因此，需要其他方法。我们假设，与产后过度营养的个体相比，产前营养不良的个体（但不是产后过度营养的个体）适应了食物有限的生活，这在反映饥饿、应激和食物短期丰富的条件下是显而易见的。在这项研究中，妊娠双羊在妊娠最后三个月接受满足 100%（NORM）或 50%（LOW）能量和蛋白质需求的饮食。双胎后代在 3 天至 6 个月龄（大约青春期）期间接受正常中等（CONV）饮食或高碳水化合物高脂肪（HCHF）饮食，此后直至 2 岁（青年期；仅女性）接受相同的中等饮食，结果分为四组：NORM-CONV、LOW-CONV、NORM-HCHF 和 LOW-HCHF。在 6 个月和 2 岁时，分别对其进行禁食和丙酸盐（营养丰富）和肾上腺素挑战。在 6 个月龄时，产后 HCHF 饮食暴露导致代谢改变，反映为高甘油三酯血症和胰腺β细胞分泌改变。无论产后饮食如何，产前营养不良与 2 岁成年人禁食时瘦素、IGF1 和皮质醇的意外内分泌反应有关（与对照组相比缺乏或相反的反应）。总之，HCHF 饮食干扰了β细胞功能，而母体营养不良除了导致激素反应异常外，对 LOW 后代没有任何变化，这表明胎儿编程干扰了重要内分泌轴的下丘脑整合。
