Role of the Omentum in the Treatment of Morbid Obesity

肥胖通常与胰岛素抵抗和炎性细胞因子的异常产生有关。中心性肥胖 是2型糖尿病(T2 DM)和心血管并发症的主要风险。脂肪 组织，尤其是大网膜(脂肪细胞和常驻巨噬细胞)会释放几种细胞因子。减肥手术和 具体地说，Roux-en-Y胃分流术(RYGB)是唯一能够持续减轻体重的方法。我们的研究和 其他人的研究表明，RYGB在高比例患者中逆转T2 DM是有效的。其作用机制 仍然不为人所知。我们有证据表明，手术后体重减轻并不是新陈代谢的唯一机制。 改进。改善发生在停药后很早(10天内)，并在任何显著的减肥之前；它们是 与内脏脂肪分布有关，并存在种族偏见，非洲裔美国人表现出迟钝和更多的延迟 回答比高加索人更多。这项应用的中心假设是治疗后胰岛素敏感性的改善 减肥手术是有种族偏见的，在术后早期(10-30天)就开始了，并受到 能量相关多肽的分泌，而长期效应(大于1个月)是通过下调调节来调节的 炎症因子的作用。此外，我们假设，切除大网膜与减肥联合 手术增强了胰岛素抵抗的逆转，并将缩小种族差异，以应对肥胖 做手术。我们建议对高加索人和非裔美国人病态肥胖患者进行一项随机研究，以评估 葡萄糖和脂肪酸代谢。患者将被随机分成两组，一组仅使用RYGB，另一组使用RYGB RYGB加大网膜切除术。提出了三个具体目标。在具体目标1中，我们将确定 RYGB治疗后代谢改善。具体地说，我们将研究与能量相关的分泌和活动的变化。 多肽和炎症反应。特定目标2探索迟钝/延迟代谢的机制 RYGB治疗后非裔美国患者的改善。我们将研究两个种族差异的遗传基础。 对肌肉、内脏和外周脂肪组织进行微阵列分析。我们将探索居民的角色 巨噬细胞在介导相关炎症反应中的作用。具体目标3将决定是否联合大网膜切除术 RYGB加速并维持了改善，特别是在非裔美国人人口中。这些研究包括 测定区域脂肪储存，脂肪细胞大小，组织巨噬细胞含量和巨噬细胞基因表达，每日和 食物诱导的脂肪因子(瘦素、抵抗素和脂联素)和能量调节多肽的分泌，如Ghrelin和 PYY。参数将与炎症标志物(例如，CRP、IL-6、TNF-O2R等)的时间依赖变化相关。 以及使用高胰岛素正糖钳的组织胰岛素反应性。

Obesity is often associated with insulin resistance and abnormal production of inflammatory cytokines. Central obesity represents a major risk for the development of type 2 diabetes mellitus (T2DM) and cardiovascular complications. Adipose tissue and especially omentum (adipocytes and resident macrophages) release several cytokines. Bariatric surgery and specifically Roux-en-Y gastric bypass (RYGB) is the only modality that results in sustained weight loss. Our studies and those of others demonstrate that RYGB is effective in reversing T2DM in a high proportion of patients. The mechanisms remain unknown. We have evidence showing that weight loss after surgery is not the sole mechanism behind the metabolic improvements. The improvements occur very early (within 10 days) postop and precede any significant weight loss; they are related to visceral fat distribution and are racially biased, with African Americans showing blunted and more delayed responses than Caucasians. The central hypotheses of this application is that improvements in insulin sensitivity after bariatric surgery are racially biased and 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. Additionally, we hypothesize that the removal of the omentum in combination with bariatric surgery enhances the reversal of the insulin resistance and will diminish the racial differences in response to bariatric surgery. We propose a randomized study in Caucasian and African American morbidly obese patients to evaluate changes in glucose and fatty acid metabolism. Patients will be randomized to two groups, one with RYGB alone and the second with RYGB with omentectomy. Three specific aims are proposed. In specific aim 1, we will determine the mechanism for the metabolic improvements after RYGB. Specifically, we will examine alterations in the secretion and action of energy related peptides and inflammatory responses. Specific aim 2 explores the mechanism for the blunted/delayed metabolic improvement after RYGB in African American patients. We will examine the genetic basis for differences in the two races using microarray analysis of muscle and visceral and peripheral adipose tissues. We will explore the role of resident macrophages in mediating associated inflammatory responses. Specific aim 3 will determine if combining omentectomy with RYGB accelerates and sustains improvements especially in the African American population. The studies include determination of regional fat stores, adipocyte size, tissue macrophage content and macrophage gene expression, diurnal and food-induced secretion of adipokines (leptin, resistin and adiponectin) and of energy regulating-peptides such as ghrelin and PYY. Parameters will be correlated with time dependent changes in inflammatory markers (e.g. CRP, IL-6, TNF-O2R, etc.) and with tissue insulin responsiveness using hyperinsulinemic euglycemic clamps.