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Diacylglycerol kinase ? deficiency preserves glucose tolerance and modulates lipid metabolism in obese mice.


ABSTRACT: 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. DGK? 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 DGK? in the regulation of energy and glucose homeostasis in relation to diet-induced insulin resistance and obesity using DGK?-KO and wild-type mice. Lipidomic analysis revealed elevated unsaturated and saturated DAG species in skeletal muscle of DGK? 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 DGK? KO mice. Thus, the increased intracellular lipids in skeletal muscle from DGK? 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, DGK? plays a role in glucose and energy homeostasis by modulating lipid metabolism in skeletal muscle.

SUBMITTER: Manneras-Holm L 

PROVIDER: S-EPMC5408609 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Diacylglycerol kinase ε deficiency preserves glucose tolerance and modulates lipid metabolism in obese mice.

Mannerås-Holm Louise L   Schönke Milena M   Brozinick Joseph T JT   Vetterli Laurène L   Bui Hai-Hoang HH   Sanders Philip P   Nascimento Emmani B M EBM   Björnholm Marie M   Chibalin Alexander V AV   Zierath Juleen R JR  

Journal of lipid research 20170228 5


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 energ  ...[more]

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