Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
PLoS One. 2011;6(9):e25261. doi: 10.1371/journal.pone.0025261. Epub 2011 Sep 28.
Intrauterine and postnatal overnutrition program hyperphagia, adiposity and glucose intolerance in offspring. Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene have been linked to increased risk of obesity. FTO is highly expressed in hypothalamic regions critical for energy balance and hyperphagic phenotypes were linked with FTO SNPs. As nutrition during fetal development can influence the expression of genes involved in metabolic function, we investigated the impact of maternal obesity on FTO.
Female Sprague Dawley rats were exposed to chow or high fat diet (HFD) for 5 weeks before mating, throughout gestation and lactation. On postnatal day 1 (PND1), some litters were adjusted to 3 pups (vs. 12 control) to induce postnatal overnutrition. At PND20, rats were weaned onto chow or HFD for 15 weeks. FTO mRNA expression in the hypothalamus and liver, as well as hepatic markers of lipid metabolism were measured.
At weaning, hypothalamic FTO mRNA expression was increased significantly in offspring of obese mothers and FTO was correlated with both visceral and epididymal fat mass (P<0.05); body weight approached significance (P = 0.07). Hepatic FTO and Fatty Acid Synthase mRNA expression were decreased by maternal obesity. At 18 weeks, FTO mRNA expression did not differ between groups; however body weight was significantly correlated with hypothalamic FTO. Postnatal HFD feeding significantly reduced hepatic Carnitine Palmitoyltransferase-1a but did not affect the expression of other hepatic markers investigated. FTO was not affected by chronic HFD feeding.
Maternal obesity significantly impacted FTO expression in both hypothalamus and liver at weaning. Early overexpression of hypothalamic FTO correlated with increased adiposity and later food intake of siblings exposed to HFD suggesting upregulation of FTO may contribute to subsequent hyperphagia, in line with some human data. No effect of maternal obesity was observed on FTO in adulthood.
宫内和产后营养过剩会导致后代过度进食、肥胖和葡萄糖不耐受。脂肪质量和肥胖相关（FTO）基因的单核苷酸多态性（SNP）与肥胖风险增加有关。FTO 在对能量平衡至关重要的下丘脑区域高度表达，并且与 FTO SNP 相关的过度进食表型。由于胎儿发育过程中的营养可以影响参与代谢功能的基因的表达，因此我们研究了母体肥胖对 FTO 的影响。
雌性 Sprague Dawley 大鼠在交配前、妊娠和哺乳期接受标准饮食（Chow）或高脂肪饮食（HFD）5 周。在出生后第 1 天（PND1），一些窝仔被调整为 3 只（对照组为 12 只）以诱导产后营养过剩。在 PND20，大鼠断奶后接受 Chow 或 HFD 喂养 15 周。测量下丘脑和肝脏中的 FTO mRNA 表达以及肝脏脂质代谢标志物。
在断奶时，肥胖母亲的后代下丘脑 FTO mRNA 表达显著增加，FTO 与内脏和附睾脂肪量均相关（P<0.05）；体重接近显著水平（P=0.07）。母体肥胖降低了肝 FTO 和脂肪酸合成酶 mRNA 的表达。在 18 周时，各组之间的 FTO mRNA 表达没有差异；然而，体重与下丘脑 FTO 显著相关。产后 HFD 喂养显著降低了肝肉碱棕榈酰转移酶-1a，但不影响所研究的其他肝脏标志物的表达。慢性 HFD 喂养对 FTO 没有影响。
母体肥胖在断奶时显著影响下丘脑和肝脏中的 FTO 表达。早期下丘脑 FTO 的过度表达与增加的肥胖和后来暴露于 HFD 的兄弟姐妹的食物摄入量相关，这表明 FTO 的上调可能导致随后的过度进食，与一些人类数据一致。在成年期，母体肥胖对 FTO 没有影响。
