Abstract: Series 104, Lecture 2

The Harvey Lectures Series 104 (2008—2009)

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Lecture #2: Thursday, November 20, 2008 — Time and Location

Transcriptional Control of Energy Homeostatis in Health and Disease

Bruce Spiegelman, PhD

Bruce Spiegelman, PhD

Professor of Cell Biology

Dana-Farber Cancer Institute, Harvard Medical School

Boston, Massachusetts

Dr Spiegelman's Website

Obesity arises from an imbalance between food intake and energy expenditure. My group has studied the molecular basis of adipose cell development, both white and brown fat. Since brown fat cells are devoted exclusively to the dissipation of chemical energy in the form of heat, as a defense against cold and obesity, we have turned our attention to understanding the transcriptional basis of brown fat determination. We have recently identified PRDM16 as a dominant regulator of brown fat identity. Gain of function experiments show that this large co-regulatory protein can turn on a full brown fat program in white fat precursor cells. Most recently, we have found that experimental knock-down of PRDM16 in primary brown fat precursor cells causes them to differentiate into bona fide skeletal muscle cells. Lineage tracing analysis in mice indicates that putative myoblasts give rise to skeletal muscle and brown, fat but not white fat. PRDM16 controls this program by interacting with an co-activating both PPAR-gamma and PGC-1 alpha. These data show that brown fat can be considered a derivative of skeletal muscle, and that prdm16 controls brown fat fate. I will also discuss how these findings might be translated into new approaches to human metabolic disease.