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.
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