Methods and Compositions for Inducing Brown Adipogenesis

Joslin Diabetes Center, Inc.
posted on 03/09/2009

The most common fat cells are white adipose tissue (WAT) cells, which have a thin ring of cytoplasm surrounding a lipid or fat droplet. WAT is found underneath the skin and provides heat insulation, cushioning against shock and jarring, and energy reserves. An average lean person has roughly 20 to 40 billion WAT cells, and an obese person can have up to ten times more WAT than the average lean person. The less common fat cells are the brown adipose tissue (BAT) cells. Energy expenditure for thermogenesis in BAT serves either to maintain body temperature in the cold or to waste food energy. It has roles in thermal balance and energy balance, and when defective, is usually associated with obesity. BAT is usually atrophied in obese animals. The importance of BAT in overall energy homeostasis is underscored by the finding that ablation of BAT in mice results in severe obesity accompanied by insulin resistance, hyperglycemia, hyperlipidemia, and hypercholesterolemia. One potential avenue for therapeutic modulation of a person’s weight might be to alter the balance between WAT and BAT cells. The inventors have discovered that several members of a well-known family of protein factors are involved in adipocyte differentiation. In their original research, it was found that treatment of pluripotent mesenchymal stem cells with specific molecules in this family triggers commitment of the stem cells to the brown adipocyte lineage. More recently, the inventors have seen the same effect in other stem cell populations, including a population of cells believed to play an important role in adipocyte differentiation in vivo. The invention therefore comprises methods for decreasing fat stores or treating weight gain or insulin resistance, by treating isolated stem cell populations with a factor from this family and implanting the resulting cell population into the patient.