reducing glycosphingolipid content in adipose tissue of obese mice restores insulin sensitivity, adipogenesis and reduces inflammation减少肥胖小鼠脂肪组织鞘糖脂含量恢复胰岛素敏感性,脂肪形成,减少炎症.pdfVIP

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reducing glycosphingolipid content in adipose tissue of obese mice restores insulin sensitivity, adipogenesis and reduces inflammation减少肥胖小鼠脂肪组织鞘糖脂含量恢复胰岛素敏感性,脂肪形成,减少炎症.pdf

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reducing glycosphingolipid content in adipose tissue of obese mice restores insulin sensitivity, adipogenesis and reduces inflammation减少肥胖小鼠脂肪组织鞘糖脂含量恢复胰岛素敏感性,脂肪形成,减少炎症

Reducing Glycosphingolipid Content in Adipose Tissue of Obese Mice Restores Insulin Sensitivity, Adipogenesis and Reduces Inflammation 1 2 1 1 1 Marco van Eijk *, Jan Aten , Nora Bijl , Roelof Ottenhoff , Cindy P. A. A. van Roomen , Peter F. 1 1 1 3 Dubbelhuis , Ingar Seeman , Karen Ghauharali-van der Vlugt , Hermen S. Overkleeft , Cynthia 4 1 1 Arbeeny , Albert K. Groen , Johannes M. F. G. Aerts 1 Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, 2 Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, 3 Department of Organic Chemistry, Gorleaus Institute, University of Leiden, Leiden, The Netherlands, 4 Genzyme Corporation, Framingham, Massachusetts, United States of America Abstract Adipose tissue is a critical mediator in obesity-induced insulin resistance. Previously we have demonstrated that pharmacological lowering of glycosphingolipids and subsequently GM3 by using the iminosugar AMP-DNM, strikingly improves glycemic control. Here we studied the effects of AMP-DNM on adipose tissue function and inflammation in detail to provide an explanation for the observed improved glucose homeostasis. Leptin-deficient obese (LepOb) mice were fed AMP-DNM and its effects on insulin signalling, adipogenesis and inflammation were monitored in fat tissue. We show that reduction of glycosphingolipid biosynthesis in adipose tissue of LepOb mice restores insulin signalling in isolated ex vivo insulin-stimulated adip