title: The Crucial Role of C18-Cer in Fat-Induced Skeletal Muscle Insulin Resistance.
abstract: OBJECTIVE
  Muscle bioactive lipids accumulation leads to several disorder states. The most common are insulin resistance (IR) and type 2 diabetes. There is an ongoing debate which of the lipid species plays the major role in induction of muscle IR. Our aim was to elucidate the role of particular lipid group in induction of muscle IR.
  
  
  METHODS
  The analyses were performed on muscle from the following groups of rats: 1. Control, fed standard diet, 2 HFD, fed high fat diet, 3. HFD/Myr, fed HFD and treated with myriocin (Myr), an inhibitor of ceramide de novo synthesis. We utilized [U13C] palmitate isotope tracer infusion and mass spectrometry to measure content and synthesis rate of muscle long-chain acyl-CoA (LCACoA), diacylglycerols (DAG) and ceramide (Cer).
  
  
  RESULTS
  HFD led to intramuscular accumulation of LCACoA, DAG and Cer and skeletal muscle IR. Myr-treatment caused decrease in Cer (most noticeable for stearoyl-Cer and oleoyl-Cer) and accumulation of DAG, possibly due to re-channeling of excess of intramuscular LCACoA towards DAG synthesis. An improvement in insulin sensitivity at both systemic and muscular level coincided with decrease in ceramide, despite elevated intramuscular DAG.
  
  
  CONCLUSIONS
  The improved insulin sensitivity was associated with decreased muscle stearoyl- and oleoyl-ceramide content. The results indicate that accumulation of those ceramide species has the greatest impact on skeletal muscle insulin sensitivity in rats.
authors.affiliation: Department of Hygiene, Epidemiology and Metabolic Disorders, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Agnieszka U
authors.initials: AU
authors.lastname: Blachnio-Zabielska
authors.forename: Marta
authors.initials: M
authors.lastname: Chacinska
authors.forename: Mikkel H
authors.initials: MH
authors.lastname: Vendelbo
authors.forename: Piotr
authors.initials: P
authors.lastname: Zabielski
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002518:Ceramides / Q000494:pharmacology*; D003066:Coenzyme A Ligases / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D005227:Fatty Acids / Q000097:blood; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D025341:Principal Component Analysis; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000214:Acyl Coenzyme A; D002518:Ceramides; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D007328:Insulin; D026901:Membrane Transport Proteins; D008687:Metformin; D003066:Coenzyme A Ligases; D005947:Glucose; C001996:thermozymocidin