Maloney Chris A, Gosby Alison K, Phuyal Jenny L, Denyer Gareth S, Bryson Janet M, Caterson Ian D
Human Nutrition Unit, School of Molecular and Microbial Biosciences, University of Sydney, Sydney, New South Wales, Australia.
Obes Res. 2003 Mar;11(3):461-8. doi: 10.1038/oby.2003.63.
Intrauterine growth restriction is associated with increased prevalence of the metabolic syndrome in adult life, including increased adiposity. The aim of this study was to investigate if maternal protein energy malnutrition is associated with changes in expression of genes involved in fat partitioning in weanling rats.
Time-mated mothers were placed on one of two isocaloric diets, low protein [(LP), 8% protein] or control (20% protein). All mothers remained on the diet throughout pregnancy and lactation. A third group received control for 2 weeks and was switched to LP for the last week of pregnancy and lactation [late low protein (LLP) group]. Offspring were analyzed at weaning for serum glucose, nonesterified fatty acids, triglyceride, and insulin. Expression of the genes acetyl-coenzyme A carboxylase, fatty acid synthase, and carnitine palmitoyl transferase 1 were measured in liver, quadriceps muscle, and subcutaneous white adipose tissue using semiquantitative reverse transcription-polymerase chain reaction.
LLP and LP offspring were shorter, weighed less, had reduced serum insulin and nonesterified fatty acids, and had increased serum glucose, serum triglycerides, and hepatic triglycerides. Hepatic gene expression of acetyl-coenzyme A carboxylase and fatty acid synthase was increased 2-fold in LLP and LP offspring (p < 0.001). These changes were not seen in muscle or subcutaneous white adipose tissue. CPT-1 gene expression was unaltered in all tissues examined.
Maternal protein energy malnutrition programs gene expression of lipogenic enzymes in the liver of weanling offspring in a manner favoring fat synthesis that may predispose these offspring to fat accumulation and insulin resistance later in life.
宫内生长受限与成年后代谢综合征患病率增加有关，包括肥胖增加。本研究的目的是调查母体蛋白质能量营养不良是否与断奶大鼠脂肪分配相关基因的表达变化有关。
将经定时交配的母鼠置于两种等热量饮食之一，低蛋白（[LP]，8%蛋白质）或对照（20%蛋白质）。所有母鼠在整个怀孕和哺乳期都维持该饮食。第三组接受2周的对照饮食，在怀孕和哺乳期的最后一周改为低蛋白饮食[晚期低蛋白（LLP）组]。断奶时对后代进行血清葡萄糖、非酯化脂肪酸、甘油三酯和胰岛素分析。使用半定量逆转录-聚合酶链反应测量肝脏、股四头肌和皮下白色脂肪组织中乙酰辅酶A羧化酶、脂肪酸合酶和肉碱棕榈酰转移酶1基因的表达。
LLP和LP后代更矮小、体重更轻，血清胰岛素和非酯化脂肪酸降低，血清葡萄糖、血清甘油三酯和肝脏甘油三酯升高。LLP和LP后代肝脏中乙酰辅酶A羧化酶和脂肪酸合酶的基因表达增加了2倍（p < 0.001）。这些变化在肌肉或皮下白色脂肪组织中未观察到。在所有检测的组织中，CPT-1基因表达未改变。
母体蛋白质能量营养不良以有利于脂肪合成的方式调控断奶后代肝脏中脂肪生成酶的基因表达，这可能使这些后代在以后的生活中易发生脂肪堆积和胰岛素抵抗。
