Cell Culture Approaches to Generating Brown Adipose Tissue for Autologous Transplantation

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). This proposal is a feasibility study to define a prototype source and culture system for the generation of human BAT for autologous transplantation therapy. We have recently identified a brown adipocyte progenitor cell population in human muscle, and propose to isolate and characterize the best brown adipocyte progenitor sub-population from human muscle biopsies, expand these cells, and establish the optimal conditions for in vitro differentiation that can generate approximately 50 grams of BAT cells for transplantation.