Erhuma Aml, Bellinger Leanne, Langley-Evans Simon C, Bennett Andrew J
School of Biomedical Sciences, University of Nottingham, Queens Medical Centre, Nottingham NG7 2UH, UK.
Br J Nutr. 2007 Sep;98(3):517-24. doi: 10.1017/S0007114507721505. Epub 2007 Apr 19.
Fetal undernutrition programmes risk of later metabolic disorders. Postnatal factors modify the programmed phenotype. This study aimed to assess the effects of a postnatal high-fat (HF) challenge on body weight gain, adiposity and gene expression following prenatal undernutrition. Pregnant rats were fed either a control diet or a low-protein (LP) diet, targeted at days 0-7 (LPE), days 8-14 (LPM), or days 15-22 (LPL) gestation. At 12 weeks of age offspring were either fed standard laboratory chow diet (4.13 % fat), or a 39.5 % fat diet, for 10 weeks. LP exposure had no effect on weight gain or abdominal fat in males. Females exposed to LP diet in utero exhibited a similar weight gain on HF diet as on the chow diet. Programming of fat deposition was noted in LPE females and males of the LPM and LPL groups (P = 0.019). Hypothalamic expression of galanin mRNA was similar in all groups, but expression of the galanin-2 receptor was modified by LP exposure in female offspring. Hepatic expression of sterol response element binding protein (SREBP-1c) was decreased by LP at both the mRNA (P = 0.008) and protein (P < 0.001) level. HF feeding increased expression of SREBP-1c mRNA three-fold in controls, with little response noted in the LP groups. Interactions of factors such as postnatal diet, age and sex act together with prenatal factors to determine metabolic function and responsiveness at any stage of postnatal life. This study further establishes a role for prenatal nutrition in programming the genes involved in lipid metabolism and appetite regulation.
胎儿期营养不足会增加日后发生代谢紊乱的风险。出生后的因素会改变这种程序化的表型。本研究旨在评估出生后高脂（HF）刺激对产前营养不足后体重增加、肥胖及基因表达的影响。将怀孕大鼠在妊娠第0 - 7天（LPE）、第8 - 14天（LPM）或第15 - 22天（LPL）分别给予对照饮食或低蛋白（LP）饮食。在12周龄时，将后代分别给予标准实验室普通饲料（脂肪含量4.13%）或脂肪含量39.5%的饲料，持续10周。LP暴露对雄性大鼠的体重增加或腹部脂肪没有影响。子宫内暴露于LP饮食的雌性大鼠在HF饮食上的体重增加与在普通饲料上相似。在LPE组的雌性大鼠以及LPM和LPL组的雄性大鼠中发现了脂肪沉积的程序化现象（P = 0.019）。所有组中甘丙肽mRNA的下丘脑表达相似，但甘丙肽-2受体的表达在雌性后代中因LP暴露而发生改变。LP使肝脏中固醇调节元件结合蛋白（SREBP-1c）的mRNA（P = 0.008）和蛋白（P < 0.001）水平均降低。HF喂养使对照组中SREBP-1c mRNA的表达增加了三倍，而LP组几乎没有反应。出生后饮食、年龄和性别等因素的相互作用与产前因素共同作用，决定了出生后任何阶段的代谢功能和反应性。本研究进一步证实了产前营养在调控参与脂质代谢和食欲调节的基因方面的作用。
