• 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 ]
  

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