Authors: X F Gao W Chen X P Kong A M Xu Z G Wang G Sweeney D Wu
Publish Date: 2009/02/18
Volume: 52, Issue: 5, Pages: 912-920
Abstract
Carnitine palmitoyltransferase1 CPT1c is a novel isoform in the CPT1 family and is found specifically in the brain Cpt1c knockout KO mice are more susceptible to highfat diet HFDinduced obesity However the underlying mechanism of this phenotype and the question of whether CPT1c is involved in the pathogenesis of dietinduced insulin resistance are unclearAfter 8 weeks of HFD feeding Cpt1c KO mice developed a phenotype of more severe insulin resistance than that in wildtype controls The increased susceptibility of Cpt1c KO mice to HFDinduced insulin resistance was independent of obesity Impaired glucose tolerance in Cpt1c KO mice was attributable to elevated hepatic gluconeogenesis and decreased glucose uptake in skeletal muscle These effects correlated with decreased hepatic and intramuscular fatty acid oxidation and expression of oxidative genes as well as with elevated triacylglycerol content in these tissues Interestingly Cpt1c deletion caused a specific elevation of hypothalamic CPT1a and CPT1b isoform expression and activity We demonstrated that elevated plasma NEFA concentration is one mechanism via which this compensatory effect is inducedThese results further establish the role of CPT1c in controlling wholebody glucose homeostasis and in the regulation of hypothalamic Cpt1 isoform expression We identify changes in hepatic and skeletal muscle glucose metabolism as important mechanisms determining the phenotype of Cpt1c KO mice
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