More fat cells, less fat?

A fat-based hormone, the first of its kind to be identified, may regulate the body's metabolic rate, according to a linkurl:report;http://www.cell.com/content/article/abstract?uid=PIIS0092867408010143 in this week's __Cell.__ The results paradoxically suggest that aspects of metabolic disease could be controlled by spurring the production of new fat cells. "There's a strong dogma that excess fat is bad in every form, that the effects will always be negative," said principal investigator Gokhan Hotamisligil from the Harvard School of Public Health. "In these animals the hypothesis did not hold up." Hotamisligil and colleagues were studying lipid chaperones, which control the storage of fat inside cells. When they created knockout mice missing two of the chaperones, they saw systemic changes in metabolism as well as increased production of new fat cells. Since the new fat seemed to be causing changes in insulin sensitivity in organs such as muscle and liver, the researchers suspected it was releasing a hormone that traveled to these distant organs to cause an effect. Their search for the hormone, however, was "not fruitful," Hotamisligil told __The Scientist.__ In a last ditch effort, they decided to look at the lipid dissolved in the blood. While it's known that fat tissue produces hormones and that signaling proteins help regulate metabolism, lipids have not traditionally been thought of as signaling molecules (read our September 2007 feature on fat signaling molecules linkurl:here.;http://www.the-scientist.com/article/display/53541/ ) What made the experiments difficult, said Hotamisligil, is that, "Lipids are nasty molecules to work with." Techniques that have allowed large-scale analysis of genes and proteins are not prevalent in lipid research, so first author Haiming Cao and colleagues had the laborious task of characterizing the lipid fraction by liquid and gas chromatography and mass spectrometry of more than 400 lipid species. One lipid stood out in their analyses: C16:1n7-palmitoleate. In mice, the researchers found, the substance acted like insulin. "It potentiates insulin action and allows it to signal much better," said Hotamisligil. Palmitoleate may seem like an attractive target for those suffering from metabolic diseases such as diabetes, but administered directly, it "may not establish continuous efficacy," said Hotamisligil. Instead he thinks that new fat cell formation, which naturally increases palmitoleate levels, could lead to better control of insulin and possibly linkurl:decreased body weight.;http://www.the-scientist.com/2008/01/1/28/1/ That means the two lipid chaperones the researchers started with may provide better targets. "This is a very interesting and provocative study," wrote Alan Attie, a professor of metabolic diseases at the University of Wisconsin-Madison who was not involved in the work. He added that it "raises many questions that will keep people busy for quite some time," such as identifying the tissues that produce palmitoleate, and the tissues it targets to induce the insulin sensitivity boost.

More fat cells, less fat?

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