Dr. Bruce M. Spiegelman
Stanley J. Korsmeyer Professor of Cell Biology and Medicine
Dana-Farber Cancer Institute, Harvard Medical School
Transcriptional Control of Brown and Beige Fat: Toward a New Generation of Therapeutics
Our group has been interested in the development of both white and brown fat, particularly at the level of gene transcription. We have now found that PGC1 expression in muscle (and exercise) control the expression of Fndc5, a cell membrane protein. Fndc5 is proteolysed to give rise to a new secreted protein of 112 amino acids that we have called irisin. Irisin circulates in both muse and man, and even mild elevations of irisin activates the browning of white fat, causing increased energy expenditure and reducing obesity. Most recently we have produced versions of the irisin protein that are very active in both cultured cells and in vivo.
Irisin acts on a specific cell type called beige adipose cells. We isolated and cloned these cells from the subcutaneous fat of mice and have now made immortalized beige cell lines. Importantly, we show that the brown fat previously identified in adult humans corresponds much more closely to beige fat than the brown fat of mice. Finally we have found that primary beige fat precursors can be sorted from mice using the cell surface marker cd137. The cells are much more sensitive to irisin than the low cd137 preadipocytes. Finally, we will finally discuss therapy involving beige fat and irisin in humans.
Bruce M. Spiegelman is the Stanley J. Korsmeyer Professor of Cell Biology and Medicine at Harvard Medical School and Dana-Farber Cancer Institute. Dr.Spiegelman received a B.S. with highest honors from the College of William and Mary in 1974, his PhD in biochemistry from Princeton University in 1978, and completed postdoctoral work at MIT. He joined Harvard Medical School and Dana-Farber Cancer Institute in 1982. His research focuses on fat cell biology, diabetes and muscular diseases. Dr.Spiegelman has been honored with many awards including Bristol-Myers Squibb Award for Distinguished Achievement in Metabolic Research; the Solomon Berson Award, American Physiological Society; the Rolf Luft Award in Endocrinology, Karolinska Institute (Sweden); the Trans-Atlantic Medal, British Endocrine Society; the Naomi Berrie Award for Outstanding Achievement in Diabetes Research, Columbia University; the Banting Medal for Scientific Achievement, American Diabetes Association, 2012. In 2002 Dr. Spiegelman was elected to the American Academy of Arts and Sciences and the National Academy of Science.