Muscle-like fat?

All fat is not not created equal: In the past couple years researchers have come to realize that there's good fat and bad fat, and a study in this week's __Nature__ points to a biological reason for this difference. White fat, the main type of fat in the body, develops from fat precursor cells and stores excess energy. Brown fat, however, burns energy rather than storing it, and the new findings suggest it originates from muscle precursor cells. That means that "brown fat is one gene away from

Written byEdyta Zielinska
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All fat is not not created equal: In the past couple years researchers have come to realize that there's good fat and bad fat, and a study in this week's __Nature__ points to a biological reason for this difference. White fat, the main type of fat in the body, develops from fat precursor cells and stores excess energy. Brown fat, however, burns energy rather than storing it, and the new findings suggest it originates from muscle precursor cells. That means that "brown fat is one gene away from skeletal muscle," said linkurl:Bruce Spiegelman;http://www.the-scientist.com/article/display/21425/ from the Dana-Farber Cancer Institute and Harvard Medical School, who led the study. Once thought to be important only for keeping infants and small mammals warm, brown fat may play a role in maintaining normal body weight in humans. Mice that have stores of brown fat are leaner than controls, and become obese when brown fat is knocked out. Brown fat stores have been difficult to find in adult humans, but linkurl:recent studies;http://www.ncbi.nlm.nih.gov/pubmed/17473055?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum using PET scans have identified several brown fatdepots, bolstering the idea that brown fat plays an important role in adult physiology as well. In linkurl:previous work,;http://www.ncbi.nlm.nih.gov/pubmed/17618855?ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Spiegelman had identified the gene PRDM-16 as the "master regulator" of the brown fat's genetic program. (He wrote about the experiments that led him to PRDM-16 in our linkurl:January issue;http://www.the-scientist.com/2008/01/1/28/1/ ). So his group set out to further define how the gene switches on brown fact cell production. Researchers had long assumed that white fat and brown fat come from the same fat cell precursor. So when first author Patrick Seale and colleagues knocked down PRDM-16 via RNA interference in brown fat taken from mice, they expected it turn into white fat. Instead "we got muscle," said Spiegelman. To double check their results, researchers took myogenic cells -- muscle cells precursors -- and forced PRDM-16 expression. This time, they turned the cells fated to be muscle cells into brown fat cells. When they tracked the development of myogenic cells in vivo, they saw the cells develop into brown fat or skeletal muscle, but not white fat. The results suggest that "the natural precursor cell type [for brown fat] is probably myogenic," said Spiegelman. Spiegelman believes that PRDM-16's ability to increase brown fat stores may make it a good target for linkurl:treating obesity.;http://www.the-scientist.com/2008/6/1/40/1/ Along with collaborators at the Broad Institute, his group is now searching for the natural and pharmacological triggers of the gene.
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