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

  • J. T. Tansey
    Laboratory of Cellular and Developmental Biology, Diabetes Branch, and Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892
  • C. Sztalryd
    Laboratory of Cellular and Developmental Biology, Diabetes Branch, and Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892
  • J. Gruia-Gray
    Laboratory of Cellular and Developmental Biology, Diabetes Branch, and Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892
  • D. L. Roush
    Laboratory of Cellular and Developmental Biology, Diabetes Branch, and Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892
  • J. V. Zee
    Laboratory of Cellular and Developmental Biology, Diabetes Branch, and Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892
  • O. Gavrilova
    Laboratory of Cellular and Developmental Biology, Diabetes Branch, and Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892
  • M. L. Reitman
    Laboratory of Cellular and Developmental Biology, Diabetes Branch, and Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892
  • C.-X. Deng
    Laboratory of Cellular and Developmental Biology, Diabetes Branch, and Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892
  • C. Li
    Laboratory of Cellular and Developmental Biology, Diabetes Branch, and Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892
  • A. R. Kimmel
    Laboratory of Cellular and Developmental Biology, Diabetes Branch, and Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892
  • C. Londos
    Laboratory of Cellular and Developmental Biology, Diabetes Branch, and Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892

抄録

<jats:p> Perilipin coats the lipid droplets of adipocytes and is thought to have a role in regulating triacylglycerol hydrolysis. To study the role of perilipin <jats:italic>in vivo</jats:italic> , we have created a <jats:italic>perilipin</jats:italic> knockout mouse. <jats:italic>Perilipin</jats:italic> null ( <jats:italic>peri</jats:italic> <jats:sup>−/−</jats:sup> ) and wild-type ( <jats:italic>peri</jats:italic> <jats:sup>+/+</jats:sup> ) mice consume equal amounts of food, but the adipose tissue mass in the null animals is reduced to ≈30% of that in wild-type animals. Isolated adipocytes of <jats:italic>perilipin</jats:italic> null mice exhibit elevated basal lipolysis because of the loss of the protective function of perilipin. They also exhibit dramatically attenuated stimulated lipolytic activity, indicating that perilipin is required for maximal lipolytic activity. Plasma leptin concentrations in null animals were greater than expected for the reduced adipose mass. The <jats:italic>peri</jats:italic> <jats:sup>−/−</jats:sup> animals have a greater lean 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 <jats:italic>perilipin</jats:italic> null animals are resistant to diet-induced obesity but not to glucose intolerance. The data reveal a major role for perilipin in adipose lipid metabolism and suggest perilipin as a potential target for attacking problems associated with obesity. </jats:p>

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