Department of Type 2 Diabetes Pharmacology, Novo Nordisk A/S, Maaloev, Denmark; Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
Acta Physiol (Oxf). 2014 Jan;210(1):142-53. doi: 10.1111/apha.12138. Epub 2013 Jul 12.
According to the World Diabetes Foundation, there is an urgent need to investigate the impact of maternal health and nutrition during pregnancy to understand the background for the accelerating incidence of obesity and type 2 diabetes. In this study, we specifically concentrated on the role of overfeeding during different developmental periods.
Sprague-Dawley rats were offered chow or high-fat/high-sucrose diet (chow plus chocolate and soft drink) during gestation and lactation. At birth, offspring were randomly cross-fostered within each dietary group into small and normal litter sizes until weaning, giving four dietary groups.
At postnatal day 1, offspring from high-fat/high-sucrose-fed dams were heavier and had increased hepatic triglycerides (TG), hepatic glycogen, blood glucose and plasma insulin compared with offspring from chow-fed dams. Hepatic genes involved in lipid oxidation, VLDL transport and insulin receptor were down-regulated, whereas FGF21 expression was up-regulated. Independent of postnatal litter size, offspring from high-fat/high-sucrose-fed dams aged 21 days had still increased hepatic TG and up-regulated FGF21 expression, while plasma insulin started to decrease. Litter size reduction in offspring from high-fat/high-sucrose-fed dams further increased body weight and adiposity, and up-regulated genes involved in hepatic mitochondrial lipid oxidation and VLDL transport compared with all other groups. Litter size reduction did not have any impact on body weight gain and adiposity in offspring born to chow-fed dams.
Our results suggest that supplementation of chocolate and soft drink during gestation and lactation contributes to early onset of hepatic steatosis associated with changes in hepatic gene expression and lipid handling.
根据世界糖尿病基金会的数据，迫切需要研究孕期母婴健康和营养对肥胖和 2 型糖尿病发病率上升的影响。本研究特别关注了不同发育期过度喂养的作用。
在妊娠和哺乳期，Sprague-Dawley 大鼠给予标准饮食或高脂肪/高蔗糖饮食（标准饮食加巧克力和软饮料）。出生时，根据每个饮食组的大小，将后代随机交叉寄养到小窝或正常窝中，直到断奶，共分为四个饮食组。
高脂肪/高蔗糖饮食组母鼠的后代在出生后第 1 天体重就更重，肝内甘油三酯（TG）、肝糖原、血糖和血浆胰岛素水平也更高。与标准饮食组相比，涉及脂质氧化、VLDL 转运和胰岛素受体的肝内基因表达下调，而 FGF21 的表达上调。不考虑出生后窝仔大小，21 天大的高脂肪/高蔗糖饮食组后代的肝内 TG 仍然增加，FGF21 的表达上调，而血浆胰岛素开始下降。与其他所有组相比，高脂肪/高蔗糖饮食组后代的窝仔数减少进一步增加了体重和肥胖程度，上调了与肝内线粒体脂质氧化和 VLDL 转运相关的基因表达。窝仔数减少对标准饮食组后代的体重增加和肥胖没有任何影响。
我们的研究结果表明，妊娠期和哺乳期补充巧克力和软饮料会导致与肝内基因表达和脂质代谢变化相关的早期肝脂肪变性。
