OMENTUM AND TREATMENT OF MORBID OBESITY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本应用的中心假设是，减肥手术后胰岛素敏感性的改善始于术后早期（10-30天），并由能量相关肽分泌的变化介导，而长期效应（大于1个月）是由炎症因子的下调介导的。我们推测，这些因素将表现出种族偏见的趋势，并可能是非洲裔美国人与白种人不同代谢反应的基础。此外，我们假设大网膜切除联合roux-en-y胃旁路（RYGB）手术将加速胰岛素抵抗状态的逆转，并将减少对减肥手术反应的种族差异。具体目标1：确定RYGB后代谢改善的机制我们将在术后4周检查手术的代谢影响，此时在大多数高加索受试者中观察到胰岛素敏感性的早期改善，并且BMI或身体成分的变化最小。我们将在体重明显减轻的6个月、12个月和24个月时对受试者进行研究。我们将评估RYGB后的哪些改善与特定能量调节肽和/或炎症因子的早期改变有关，哪些改善与体重减轻有关。具体目标2：探讨非裔美国人RYGB后代谢改善迟钝和延迟的机制我们将比较在匹配的实验条件下白种人和非裔美国人代谢谱的时间变化。来自两个脂肪组织仓库的基因微阵列分析将用于获得一种无偏倚的方法，这将指导数据解释。具体目的3：探讨大网膜切除术联合RYGB是否有助于加速和维持代谢改善，特别是在更难治疗的非裔美国人人群中。在一个亚组受试者中，大网膜切除术将随机联合RYGB。我们假设，接受RYGB联合网膜切除术的非裔美国人的开始时间和代谢改善的程度（如特异性目标1）将与单独接受RYGB（不切除网膜）的白种人相当。我们试图测试改善的机制，并坚持零假设，即这两个组随着时间的推移是可比较的。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The central hypotheses of this application is that improvements in insulin sensitivity following bariatric surgery begin early in the postoperative period (10-30 days) and are mediated by changes in the secretion of energy-related peptides, while the long-term effects (greater than 1 month) are mediated by down-regulation of inflammatory factors. We speculate that these factors will exhibit racially biased trends and may underlie the different metabolic responses of African Americans versus Caucasians. Additionally, we hypothesize that the removal of the omentum in combination with roux-en-y gastric bypass (RYGB) surgery will speed up the reversal of insulin resistance state and would diminish the racial differences in response to bariatric surgery. Specific Aim 1: Determine the mechanism for the metabolic improvements after RYGB We will examine the metabolic effects of the surgery at 4-weeks postoperatively, at a time when early improvements in insulin sensitivity are observed in the majority of Caucasian subjects and when changes in BMI or body composition are minimal. We will study subjects at 6, 12 and 24 months when weight loss becomes significant. We will evaluate which improvements following RYGB can be related to early alterations in specific energy-regulatory peptides and/or inflammatory factors and which simply follow the decrease in body weight. Specific Aim 2: Explore the mechanism for the blunted and delayed metabolic improvement after RYGB in African Americans We will compare the temporal changes in the metabolic profile will be made under matched experimental conditions for Caucasians and African Americans. Gene microarray analysis from two adipose tissue depots will be used to obtain an unbiased approach that will guide data interpretation. Specific Aim 3: Explore whether combining omentectomy with RYGB helps accelerate and sustain metabolic improvements especially in the more refractory African American population Removal of the greater omentum will be combined with RYGB randomly in a subgroup of subjects. We hypothesize that onset time and magnitude of the metabolic improvements (as in Specific Aim 1) in African Americans who undergo RYGB combined with omentectomy will be comparable to Caucasians undergoing RYGB alone (without omentectomy). We seek to test the mechanisms of improvement and to uphold the null hypothesis that the two said groups are comparable over time.