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Making Fat-proof Mice

mice
Source: courtesy of Baylor College of Medicine

As most dieters will tell you, fat is stubborn stuff. For individuals genetically predisposed to obesity, this fact is particularly worrisome. But findings published in the December issue of the journal Nature Genetics could eventually help fight obesity. The key, researchers say, may be targeting a fat-protecting protein known as perilipin.

Earlier studies had suggested that perilipin was involved in lipid maintenance and energy metabolism. So Lawrence Chan of Baylor College of Medicine and his colleagues set out to clarify the protein's role by genetically engineering a line of mice in which the gene that codes for perilipin had been inactivated. The team found that in comparison to normal mice (A), the perilipin-free mice had about half as much body fat, 8 percent more muscle and a consistently higher metabolic rate--despite eating 25 percent more food and leading sedentary lives. Furthermore, fat cells in perilipin-free mice were half as large as those in the normal mice. The researchers also examined the effects of perilipin in mice genetically programmed to be obese. There again the results were dramatic: the mice lacking perilipin (B) grew up to be lean and healthy, in contrast to those that produced the protein (C).

"Perilipin works by coating the surface of fat storage droplets inside fat cells, protecting them from hormone-sensitive lipase, HSL, a fat-metabolizing enzyme," Chan explains. Without perilipin, HSL burns the fat right away. "These results are very exciting because not only is perilipin active in humans, it is made almost exclusively by fat cells," he notes. Thus, drugs that target perilipin could potentially have fewer side effects than anti-obesity drugs that affect the brain or other organs. But as promising as the perilipin research seems, Chan cautions that "it will take time to move perilipin research from experiments in mice to helping humans with weight problems."

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