Bruce M. Spiegelman

I have studied the transcriptional basis of energy metabolism in mammalian systems. One of our major efforts has been to decipher the transcriptional basis of adipogenesis. This has identified the nuclear receptor PPAR gamma as a dominant regulator of fat cell differentiation and insulin sensitivity. Further work has also shown a role for this receptor in differentiation and growth of other cell types, including many epithelial cells involved in human cancer. These studies have led to clinical trials for the use of PPAR gamma ligands in several forms of human cancer. Our studies have also shown that there is important regulation of metabolism at the level of the transcriptional coactivator. PGC-1 stimulates a switch toward a more oxidative state in many tissues, including brown fat-mediated thermogenesis, muscle fiber-type switching, and many aspects of the fasted liver, including hepatic gluconeogenesis. PGC-1 is induced in liver by hormones that induce gluconeogenesis and this coactivator activates the entire program of glucose production.