Role of maternal bariatric surgery in programming cardio-metabolic disease in growth-restricted offspring

项目2格雷森摘要 母体减肥手术在子代心血管疾病规划中的作用 长期减肥和解决肥胖相关并发症的减肥手术 在最近几十年里越来越受欢迎。垂直袖状胃切除术(VSG)是一种外科减肥手术 切除80%的胃形成一条连接食道和胃的管子的手术 由于VSG手术的巨大有效性和相对简单，VSG现在是 在美国，接受VSG的人中有80%是女性，其中大约一半是 生育年龄。雌性啮齿动物的VSG具有与接受VSG的女性相似的特征。 接受过减肥手术的女性患妊娠期糖尿病的风险较低 先兆子痫和降低胎龄过大(LGA)婴儿的风险。然而，最近有报道称， 还强调了以前接受过减肥手术的女性的负面结果，包括增加 胎龄较低或早产的小于胎龄儿(SGA)或IUGR出生的风险 出生、死产或新生儿死亡。我们是第一个在我们的啮齿动物VSG模型中展示的 在没有可识别的负面结果的情况下，后代有IUGR和死亡率增加 妈的。我最新的初步数据显示，VSG患者的母体血浆睾酮水平升高 在妊娠晚期，我们假设这可能在发育过程中发挥作用 制定增加IUGR子代心脏和肾脏风险的方案。这项提议将考验这部小说 VSG水坝出生前暴露于内源性睾酮水平升高的假说 增加男性和女性IUGR后代心脏代谢异常的风险。(1)我们会 检验胎儿暴露于母体内源性睾酮水平升高的假设 VSG DAMS通过胰岛β细胞功能受损和 瘦素抵抗导致IUGR子代肥胖和高血压。(2)我们将测试 胎儿暴露于VSG水坝母体内源性睾酮水平升高的假设 程序激活肾素-血管紧张素系统导致IUGR血压升高 后代。

Project 2 Grayson ABSTRACT Role of maternal bariatric surgery in programming cardiovascular disease in offspring Bariatric surgery for long term body weight loss and resolution of obesity-associated comorbidities has gained popularity in recent decades. Vertical sleeve gastrectomy (VSG) is a surgical weight loss procedure that resects 80% of the stomach creating a tube linking the esophagus to the duodenum.Because of the great effectiveness and relative simplicity of the VSG surgery, VSG is now on the rise in the U.S. >80% of the recipients of VSG are women of whom approximately half are of child-bearing age. VSG in female rodents has similar characteristics of women undergoing VSG. Women who have undergone bariatric surgery have a lower risk of gestational diabetes and preeclampsia, and reduced risk of large-for-gestational age (LGA) babies. However, recent reports also highlight negative outcomes in women with previous bariatric surgery that include an increased risk for small-for-gestational age babies (SGA) or IUGR birth at a reduced gestational age or preterm birth, and still birth or neonatal death. We were the first to show in our model of rodent VSG, that offspring had IUGR and increased mortality in the absence of identifiable negative outcomes in the dam. My novel preliminary data indicate that maternal plasma testosterone is increased in VSG dams during late pregnancy, and we hypothesize that this could play a role in the developmental programming of increased cardio-renal risk of the IUGR offspring. This proposal will test the novel hypothesis that prenatal exposure to increased endogenous levels of testosterone in VSG dams increases the risk for cardio-metabolic abnormalities in male and female IUGR offspring. (1) We will test the hypothesis that fetal exposure to elevated maternal endogenous levels of testosterone in VSG dams programs glucose intolerance mediated by impaired pancreatic beta cell function and leptin resistance leading to obesity and hypertension in IUGR offspring. (2) We will test the hypothesis that fetal exposure to elevated maternal endogenous levels of testosterone in VSG dams programs activation of the renin-angiotensin system leading to elevated blood pressure in IUGR offspring.