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  • 标题:Diacylglycerol kinase ε deficiency preserves glucose tolerance and modulates lipid metabolism in obese mice
  • 本地全文:下载
  • 作者:Louise Mannerås-Holm ; Milena Schönke ; Joseph T. Brozinick
  • 期刊名称:JLR Papers In Press
  • 印刷版ISSN:0022-2275
  • 电子版ISSN:1539-7262
  • 出版年度:2017
  • 卷号:58
  • 期号:5
  • 页码:907-915
  • DOI:10.1194/jlr.M074443
  • 语种:English
  • 出版社:American Society for Biochemistry and Molecular Biology
  • 摘要:Diacylglycerol kinases (DGKs) catalyze the phosphorylation and conversion of diacylglycerol (DAG) into phosphatidic acid. DGK isozymes have unique primary structures, expression patterns, subcellular localizations, regulatory mechanisms, and DAG preferences. DGKε has a hydrophobic segment that promotes its attachment to membranes and shows substrate specificity for DAG with an arachidonoyl acyl chain in the sn-2 position of the substrate. We determined the role of DGKε in the regulation of energy and glucose homeostasis in relation to diet-induced insulin resistance and obesity using DGKε-KO and wild-type mice. Lipidomic analysis revealed elevated unsaturated and saturated DAG species in skeletal muscle of DGKε KO mice, which was paradoxically associated with increased glucose tolerance. Although skeletal muscle insulin sensitivity was unaltered, whole-body respiratory exchange ratio was reduced, and abundance of mitochondrial markers was increased, indicating a greater reliance on fat oxidation and intracellular lipid metabolism in DGKε KO mice. Thus, the increased intracellular lipids in skeletal muscle from DGKε KO mice may undergo rapid turnover because of increased mitochondrial function and lipid oxidation, rather than storage, which in turn may preserve insulin sensitivity. In conclusion, DGKε plays a role in glucose and energy homeostasis by modulating lipid metabolism in skeletal muscle.
  • 关键词:lipid kinase ; lipidomics ; insulin resistance ; muscle ; animal models ; obesity ; diabetes
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