Metabolic Consequences of bariatric surgery on pregnant and lactating rats and th

描述（由申请人提供）：目前，美国18.9%的育龄女性重度或病态肥胖，BMI为351。除了体重超重外，大多数人还会患上“代谢综合征”，包括胰岛素抵抗、葡萄糖耐量受损和高血压、甘油三酯和胆固醇2。对于育龄妇女而言，肥胖会增加生殖困难，包括生育能力下降、妊娠期糖尿病、高血压和先兆子痫导致母亲和后代的发病率和死亡率增加、分娩大于胎龄儿（LGA）的困难以及产后母乳容量和质量下降3 -5。此外，纵向人类和动物研究表明，母体在子宫内的环境极大地影响了后代的代谢健康，肥胖的母亲更有可能生下患有代谢综合征的孩子6 -9，而体重减轻改善了许多生育和妊娠问题以及代谢综合征的合并症10，11，通过减少食物摄入和锻炼难以实现长期的体重减轻，并且目前可用的药物治疗仅导致体重的小幅度降低。然而，一些减肥手术产生持续的体重减轻以及代谢综合征的合并症的改善，特别是在严重或病态肥胖个体中。虽然这些程序对接受者的好处是显而易见的，但一个关键问题仍然是对孕妇及其后代的影响。 拟议研究的目的是确定两种减肥手术模型对雌性大鼠生殖周期、妊娠和哺乳的影响：垂直袖状胃切除术（VSG）（一种限制性手术）和Roux-en-Y胃旁路术（RYGB）（一种限制性/吸收不良手术）。特别是，将根据妊娠和哺乳期的重要代谢需求评估这些程序的标志性副作用。此外，将确定这些程序对后代代谢健康的产后影响。 公共卫生相关性：目前，美国18.9%的女性被认为是严重或病态肥胖。越来越多的人正在寻求减肥手术，其中80%是妇女。使用减肥手术的啮齿动物模型，我们的目的是确定对母亲和后代的生殖和代谢影响。

DESCRIPTION (provided by applicant): Presently 18.9% of women of childbearing age in the US are severely or morbidly obese with a BMI e 351. Besides having excess body weight, most also develop the "metabolic syndrome" which includes insulin resistance, impaired glucose tolerance and hypertension, triglycerides and cholesterol2. For women of childbearing age, obesity carries increased reproductive difficulties including decreased fertility, increased morbidity and mortality during pregnancy to both mother and offspring due to gestational diabetes, hypertension and preeclampsia, difficulties in delivery of large-for-gestational age (LGA) infants and decreased capacity and quality of breast milk in the postpartum period3-5. Furthermore, longitudinal human and animal studies indicate that the maternal in utero environment greatly affects the metabolic health of the offspring, with obese mothers more likely to have children with the metabolic syndrome6-9 While weight loss ameliorates many fertility and pregnancy problems as well as the comorbidities of the metabolic syndrome10, 11 ,long-term weight loss is difficult to achieve through food intake reduction and exercise, and the currently available pharmacologic treatments result in only small reductions in body weight. However, several bariatric surgeries produce sustained body weight reduction as well as amelioration of the comorbidities of metabolic syndrome, especially among severely or morbidly obese individuals. Although the benefits of these procedures to the recipient are obvious, a key question remains concerning the impact on pregnant mothers and their offspring. The goal of the proposed research is to determine the impact on reproductive cyclicity, pregnancy and lactation in female rats of two models of bariatric surgery: vertical sleeve gastrectomy (VSG), a restrictive procedure, and Roux-en-Y gastric bypass (RYGB), a restrictive/malabsorptive procedure. In particular, the hallmark side effects of each of these procedures will be evaluated in light of the important metabolic needs of pregnancy and lactation. Further, the postnatal effects of these procedures on the metabolic health of the offspring will be determined. PUBLIC HEALTH RELEVANCE: Presently 18.9% of women in the U.S. are considered either severely or morbidly obese. Increasing numbers of individuals are pursuing bariatric surgery of which 80% are women. Using rodent models of bariatric surgery, we aim to determine the reproductive and metabolic effects on mother and offspring.