Human Brown Adipocyte Transplantation and In Vivo Metabolic Characterization

Obesity and its associated metabolic complications including diabetes are becoming increasingly prevalent in the general population as well as in military personnel. Brown adipose tissue (BAT) is a major site of energy expenditure through thermogenesis, which is mediated by the mitochondrial uncoupling protein-1 (UCP1). Studies in animals over the last 30 years as well as recent data in humans strongly suggest that overweight and obese individuals have a low amount of BAT, and that increasing BAT by about 50 grams in obese patients would induce strong weight loss and improve metabolic status (including glucose metabolism, lipid profiles, and cardiovascular risk). The proposed studies aim to develop a prototype system for the transplantation of autologous brown adipocytes. We intend to demonstrate that a readily generated population of human brown adipocytes can be transplanted into an animal model of human obesity and insulin resistance, and that these cells can survive and produce significant improvements in glycemic control and body composition (e.g., body weight, fat mass).