Despite progress in understanding the pathophysiology of obesity, current strategies for its medical management remain largely ineffective. Most efforts have focused on reducing caloric intake or increasing energy expenditure, either through behavior modification (e.g. dieting, regular exercise) alone, or augmented by pharmacologic efforts to decrease appetite, inhibit fat absorption, or alter metabolism. Bariatric surgery remains the only proven long term treatment of morbid obesity.
Super morbidly obese (SMO: BMI > 50) and super super morbidly obese (SSMO: BMI > 60) patients lose considerable weight, but stabilize at BMIs that are still obese or even morbidly obese after risking considerable morbidity and/or mortality. Among commonly performed bariatric surgeries, a laparoscopic two-stage procedure, in which an initial restrictive procedure is followed after a weight loss of ~100 lbs by a more complex procedure that creates malabsorption, is gaining interest. Initial studies have demonstrated very good long-term weight loss with minimal morbidity, and no operative mortality in these high risk patients.
Availability of biospecimens obtained at each stage of this protocol will allow participating scientists a unique opportunity to test in human tissues hypotheses developed in animals. Studies proposed under this application focus on fatty acids and overall fat disposition in fat depots (adipose tissue) of your body and liver, and the role of adipose tissue hormones and inflammatory processes in obesity and its associated health related issues.
Primary Outcome Measures:
- To determine the differential, depot specific effects of major weight loss (ca. 100 lb) on cell sizes,rates of LCFA uptake, lipolysis and triglyceride accumulation by adipocytes harvested during bariatric surgery from two distinct human fat depots. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
Biospecimen Description:
Blood samples and biopsies of liver as well as omental and subcutaneous fat.
| Estimated Enrollment: |
100 |
| Study Start Date: |
November 2006 |
| Estimated Study Completion Date: |
August 2011 |
| Estimated Primary Completion Date: |
August 2010 (Final data collection date for primary outcome measure) |
Despite rapidly growing interest in the pathogenesis of the obesity epidemic, the pathophysiology of obesity remain poorly understood. While studies in animals have yielded many insights, it has become clear that human obesity differs in important ways from that in rodents. Bariatric surgery offers better outcomes, but in the highest grades of obesity (BMI>50) remains a high risk undertaking with >5% operative mortality being reported when commonly performed bariatric surgical approaches are employed. By contrast, laparoscopic two-stage approach has resulted in excellent weight loss, minimal morbidity, and <1% mortality.
Availability of blood samples and biopsies of liver and omental and subcutaneous fat from each of the paired bariatric procedures in this protocol will provide a unique opportunity to study key issues in human obesity. This study tests the broad hypothesis that there are significant and as yet unrecognized differences between the pathobiology of obesity in man and rodents, the identification of which may lead to new therapeutic targets. Accordingly, to facilitate comparisons with aspects of obesity we have already investigated in animal models, we will 1. seek fat depot specific differences in LCFA disposition, macrophage infiltration and adipokine production in obesity and after surgery-induced weight loss in man, and correlate them with the presence/severity of the metabolic syndrome (MetSyn); and 2., quantify the relative significance and response to weight loss of different mechanisms contributing to hepatic steatosis and the elevated TG and reduced HDL typical of obesity and MetSyn
Purpose
