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%的育龄妇女严重或病态肥胖，体重指数为351。除了体重超标外，大多数人还会患上“代谢综合征”，包括胰岛素抵抗、糖耐量减退、高血压、甘油三酯和胆固醇。对于育龄妇女来说，肥胖增加了生殖困难，包括生育力下降，妊娠期糖尿病、高血压和先兆子痫对母子双方的发病率和死亡率增加，大胎龄婴儿分娩困难，产后母乳容量和质量下降3-5。此外，纵向的人类和动物研究表明，母亲在子宫内的环境对后代的代谢健康有很大影响，肥胖母亲更有可能生下患有代谢综合征的孩子6-9，而减肥可以改善许多生育和怀孕问题以及代谢综合征的共病10，11长期减肥很难通过减少食物摄入量和锻炼来实现，而且目前可用的药物治疗只会导致体重的小幅减轻。然而，一些减肥手术可以持续减轻体重，改善代谢综合征的共病，特别是在严重或病态肥胖的人中。尽管这些手术对接受者的好处是显而易见的，但一个关键的问题仍然是对怀孕母亲及其后代的影响。这项研究的目的是确定两种减肥手术模式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)是一种限制性手术，Roux-en-Y胃分流术(RYGB)是一种限制性/吸收不良手术。特别是，将根据怀孕和哺乳的重要新陈代谢需求来评估每一种手术的标志性副作用。此外，将确定这些程序对后代新陈代谢健康的出生后影响。

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.