Reducing glycosphingolipid content in adipose tissue of obese mice restores insulin sensitivity, adipogenesis and reduces inflammation
作者： Marco van Eijk , Jan Aten , Nora Bijl , Roelof Ottenhoff , Cindy PAA van Roomen
DOI: 10.1371/JOURNAL.PONE.0004723
关键词:
摘要: 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 studied effects AMP-DNM on adipose function inflammation detail to provide an explanation for observed improved glucose homeostasis. Leptin-deficient obese (LepOb) mice were fed its signalling, adipogenesis monitored fat tissue. We show reduction glycosphingolipid biosynthesis LepOb restores signalling isolated ex vivo insulin-stimulated adipocytes. as number larger adipocytes was reduced expression genes like peroxisome proliferator-activated receptor (PPAR) γ, responsive transporter (GLUT)-4 adipsin increased. In addition, found adiponectin gene protein increased AMP-DNM. As consequence this less inflammation, which characterized numbers macrophages (crown-like structures) levels macrophage chemo attractants monocyte-chemoattractant protein-1 (Mcp-1/Ccl2) osteopontin (OPN). conclusion, inhibition glucosylceramide adipocyte reduces animals.
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