Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production, and resistance to diet-induced obesity

Perilipin coats the lipid droplets of adipocytes and is thought to have a r ole in regulating triacylglycerol hydrolysis. To study the role of perilipi n in vivo, we have created a perilipin knockout mouse. Perilipin null (peri (-/-)) and wild-type (peri(+/+)) mice consume equal amounts of food, but th e adipose tissue mass in the null animals is reduced to approximate to 30% of that in wild-type animals. Isolated adipocytes of perilipin null mice ex hibit elevated basal lipolysis because of the loss of the protective functi on of perilipin. They also exhibit dramatically attenuated stimulated lipol ytic activity, indicating that perilipin is required for maximal lipolytic activity. Plasma leptin concentrations in null animals were greater than ex pected for the reduced adipose mass. The peri(-/-) animals have a greater l ean body mass and increased metabolic rate but they also show an increased tendency to develop glucose intolerance and peripheral insulin resistance. When fed a high-fat diet, the perilipin null animals are resistant to diet- induced obesity but not to glucose intolerance. The data reveal a major rol e for perilipin in adipose lipid metabolism and suggest perilipin as a pote ntial target for attacking problems associated with obesity.