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

项目2格雷森摘要 母亲减肥手术在规划后代心血管疾病中的作用 减肥手术用于长期体重减轻和肥胖相关合并症的解决 近几十年来越来越受欢迎。垂直袖状胃切除术（VSG）是一种手术减肥 手术切除80%的胃，建立一个连接食管和胃的管道。 由于VSG手术的巨大有效性和相对简单性，VSG现在 在美国，超过80%的VSG接受者是女性，其中大约一半是女性。 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。 接受减肥手术的女性患妊娠糖尿病的风险较低， 先兆子痫，并降低大于胎龄儿（LGA）的风险。然而，最近的报告 还强调了既往接受减肥手术的女性的负面结果， 小于胎龄儿（SGA）或IUGR出生在胎龄减少或早产的风险 分娩、死产或新生儿死亡。我们是第一个在啮齿动物VSG模型中展示的， 在没有可识别的负面结果的情况下， 大坝我的新的初步数据表明，母亲血浆睾酮增加VSG 在怀孕后期，我们假设这可能在发育中发挥作用， 计划增加IUGR后代的心肾风险。这个提议将考验小说 假设VSG母体产前暴露于增加的内源性睾酮水平 增加了胎儿宫内发育迟缓（IUGR）男女后代心脏代谢异常的风险。(1)我们将 测试胎儿暴露于母体内源性睾酮水平升高的假设， VSG母体可调节胰腺β细胞功能受损介导的葡萄糖耐受不良， 瘦素抵抗导致IUGR后代肥胖和高血压(2)我们将测试 VSG母鼠中胎儿暴露于母体内源性睾酮水平升高假设 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.