Adverse Effect of High-Fat Diet on Metabolic Programming in Offspring Born to a Murine Model of Maternal Hypertension
Adverse Effect of High-Fat Diet on Metabolic Programming in Offspring Born to a Murine Model of Maternal Hypertension
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DOI：
10.1093/ajh/hpw088
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发表时间：
2016-12-01
影响因子：
3.2
通讯作者：
Blackwell, Sean C.
中科院分区：
文献类型：
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作者：
Longo, Monica;Refuerzo, Jerrie S.;Blackwell, Sean C.
背景：我们先前报道，部分缺乏内皮型一氧化氮合酶(ENOS)基因的杂合子小鼠，由高血压eNOS(-/-)基因敲除的母亲所生的后代，会患高血压。我们假设，那些被置于高脂饮食(HFD)的后代将经历代谢程序的改变，增加他们患代谢综合征的风险。方法将eNOS(-/-)KO和野生型小鼠(eNOS(+/+)WT)杂交产生杂合子后代：母亲杂合子(Mat，eNOS(-/+))，出生于高血压eNOS(-/-)KO母亲；以及父亲杂合子(PAT，enos(-/+)，出生于血压正常的WT母亲。8周龄前，雌鼠分为MAT、eNOS(-/+)组和PAT、eNOS(-/+)组，分别为HFD组和对照组。然后获得代谢谱：体重、葡萄糖/胰岛素耐量试验(GTT、ITT)、收缩压(SBP)、血清空腹胰岛素、脂联素、瘦素水平和血脂水平。在两种日粮中，Mat、eNOS(-/+)仔猪的Gtt曲线高于PAT、eNOS(-/+)仔猪(P<；0.001)。ITT组15分钟血糖水平以MAT组高，HFD组eNOS(-/+)组高。Mat、eNOS(-/+)组胰岛素水平均高于PAT、eNOS(-/+)组。CD组Mat、eNOS(-/+)较PAT、eNOS(-/+)组SBP升高，高血压病Mat、eNOS(-/+)子代SBP进一步升高(P<；0.001)。除高密度脂蛋白水平降低外，其余各组间差异均无统计学意义(P<；0.003)。结论宫内暴露于母体高血压、出生后饲喂高脂饲料的高脂血症患者中，eNOS(-/+)增加代谢异常的易感性。因此，母体HTN是胎儿代谢程序改变的危险因素。
BACKGROUNDWe previously reported that offspring heterozygous mice partially lacking endothelial nitric oxide synthase (eNOS) gene, and born to hypertensive eNOS(-/-) Knockout mother, are hypertensive. We hypothesized that those offspring when placed on high-fat diet (HFD) will undergo altered metabolic programming increasing their risk for developing metabolic syndrome.METHODSeNOS(-/-)KO and wild-type mice (eNOS(+/+)WT) were cross-bred to produce heterozygous offspring: maternal heterozygous (Mat, eNOS(-/+)), born from hypertensive eNOS(-/-) KO mothers; and paternal heterozygous (Pat, eNOS(-/+)), born from normotensive WT mothers. Mat, eNOS(-/+) and Pat, eNOS(-/+) female were allocated to HFD or control diet (CD) until 8 weeks of age. Then a metabolic profile was obtained: weight, glucose/insulin tolerance test (GTT, ITT), systolic blood pressure (SBP), serum fasting levels of insulin, adiponectin, leptin, and a lipid panel.RESULTSWeight was not different between all offspring within each diet. GTT curve was higher in Mat, eNOS(-/+) vs. Pat, eNOS(-/+) offspring on both diet (P < 0.001). In ITT, glucose level at 15 minutes was higher in Mat, eNOS(-/+) on HFD. Insulin level was increased in Mat, eNOS(-/+) vs. Pat, eNOS(-/+) on either diet. SBP was elevated in Mat, eNOS(-/+) vs. Pat, eNOS(-/+) on CD and was further raised in Mat, eNOS(-/+) offspring on HFD (P < 0.001). No other differences were seen except for lower high-density lipoprotein levels in Mat, eNOS(-/+) fed HFD (P < 0.003).CONCLUSIONSMat, eNOS(-/+) offspring exposed in utero to maternal hypertension and fed HFD postnatally have increased susceptibility for metabolic abnormalities. Thus, maternal HTN is a risk factor for altered fetal metabolic programming.