The National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai, China.
Clin Exp Pharmacol Physiol. 2013 Sep;40(9):652-61. doi: 10.1111/1440-1681.12147.
Obesity and non-alcoholic fatty liver disease are the most common metabolic disorders in society today. Previously, we found that supplementing the maternal diet during pregnancy with chocolate and fructose has negative effects on the well-being of the offspring that were ameliorated if the offspring were fed a normal diet during postnatal life. In the present study, we investigated whether feeding offspring a high-fat diet would augment the maternal programming effects and whether extra protein supply can correct the low birth weight resulting from the chocolate-supplemented maternal diet. Pregnant Sprague-Dawley rats were divided into three groups and fed either standard chow (normal nutrition; NN), chocolate- and fructose-supplemented standard chow with casein sodium (overnutrition; ON) or the supplemented standard chow without casein sodium (malnutrition; MN) throughout pregnancy. Male offspring were weaned on either standard or high-fat chow. Dams in the MN group exhibited moderate weight gain, consumed 50% less protein (P < 0.001) but more carbohydrates during gestation and delivered pups with a 12% lower birth weight (P < 0.05) than pups in the NN group, results that are consistent with previous findings. When fed on a high-fat diet after birth, pups from dams in the MN group (MNHD) had 30% more body fat (P = 0.023) and liver triglyceride (TG) levels that were double (P < 0.01) those in offspring in the other groups, leading to fatty livers in these offspring at 14 weeks of age. Hepatic expression of the PPARα, ApoB100, MTTP, CPT1 and SREBP1c genes was significantly downregulated in the MNHD group (P < 0.05 for all), indicating changes in lipid metabolism. Although dams in the ON group exhibited marked gestational weight gain (P < 0.01), they gave birth to normal weight pups that only manifested mild increases in body fat and liver TG content (P < 0.05), without significant changes in the expression of most genes when fed with the high-fat diet. The results suggest that the extra protein supply in the form of casein sodium was able to correct some negative programming effects of the chocolate and fructose supplementation of the maternal diet, which, in conjunction with a high-fat diet in the offspring, may facilitate the onset of metabolic disorders, with impaired liver gene expression possibly a key contributor.
肥胖和非酒精性脂肪性肝病是当今社会最常见的代谢紊乱。此前，我们发现，在妊娠期间给母体饮食补充巧克力和果糖会对后代的健康产生负面影响，如果后代在产后生活中摄入正常饮食，则这种影响会减轻。在本研究中，我们研究了给后代喂食高脂肪饮食是否会增强母体编程的效果，以及额外的蛋白质供应是否可以纠正巧克力补充的母体饮食导致的低出生体重。将怀孕的 Sprague-Dawley 大鼠分为三组，分别用标准饲料（正常营养；NN）、巧克力和果糖补充的含酪蛋白酸钠的标准饲料（营养过剩；ON）或不含酪蛋白酸钠的补充标准饲料（营养不良；MN）在整个怀孕期间进行喂养。雄性后代在标准或高脂肪饲料上进行断奶。MN 组的母鼠体重增加适中，在妊娠期间消耗的蛋白质减少 50%（P < 0.001），但消耗的碳水化合物更多，并且产仔的出生体重比 NN 组低 12%（P < 0.05），这与之前的研究结果一致。出生后在高脂肪饮食下喂养时，来自 MN 组母鼠的后代（MNHD）的体脂增加了 30%（P = 0.023），肝甘油三酯（TG）水平增加了一倍（P < 0.01），与其他组相比，导致这些后代在 14 周时出现脂肪肝。MNHD 组的肝组织中 PPARα、ApoB100、MTTP、CPT1 和 SREBP1c 基因的表达显著下调（P < 0.05），表明脂质代谢发生了变化。尽管 ON 组的母鼠表现出明显的妊娠期体重增加（P < 0.01），但它们产仔的出生体重正常，只有体脂和肝 TG 含量略有增加（P < 0.05），而在给高脂肪饮食时，大多数基因的表达没有显著变化。结果表明，酪蛋白酸钠形式的额外蛋白质供应能够纠正母体饮食中巧克力和果糖补充的一些负面编程效应，这与后代的高脂肪饮食相结合，可能会促进代谢紊乱的发生，而肝基因表达受损可能是一个关键因素。
