title: The effects of the inhibition of fatty acid oxidation on pyruvate dehydrogenase complex activity in tissues of lean and obese mice.
abstract: OBJECTIVE
  To investigate the effects of an acute dose of the fatty acid oxidation inhibitor, Etomoxir, on the activity of the pyruvate dehydrogenase complex (PDHC) in different tissues in lean and obese mice.
  
  
  METHODS
  An acute dose of Etomoxir was given to mice in which obesity had been induced by an injection of gold thioglucose and to age-matched controls. The effects of time, dose and nutritional state were studied.
  
  
  METHODS
  PDHC activity in heart, quadricaps muscle, liver and white adipose tissue, glycogen content of liver and quadricaps muscle, serum glucose and insulin were measured in fed and fasted animals and in fasted animals after the ingestion of a glucose load.
  
  
  RESULTS
  Etomoxir caused an increase in the activity of the active form of the PDHC (PDHCa) in the heart, liver and WAT of fed lean mice and in the heart and liver of fed obese mice. In fasted mice, increased PDHCa was seen in the heart of lean mice and in the liver of obese mice. Etomoxir increased the PDHC response to an oral glucose challenge in the liver and WAT of lean mice and in the liver of obese mice. Etomoxir had no effect on PDHCa in quadricaps muscle. Serum glucose levels were decreased in fasted mice with no change in the fed mice. Etomoxir decreased liver glycogen content in both fed and fasted animals and inhibited the accumulation of muscle glycogen following the glucose load.
  
  
  CONCLUSIONS
  Acute inhibition of fatty acid oxidation results in tissue specific increases in PDHCa. Improvements in glucose oxidation in tissues other than skeletal muscle may contribute to the improved glucose tolerance seen following acute Etomoxir administration.
authors.affiliation: Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Bryson
authors.forename: G J
authors.initials: GJ
authors.lastname: Cooney
authors.forename: V R
authors.initials: VR
authors.lastname: Wensley
authors.forename: J L
authors.initials: JL
authors.lastname: Phuyal
authors.forename: I D
authors.initials: ID
authors.lastname: Caterson
mesh_terms: D000273:Adipose Tissue / Q000737:chemistry / Q000201:enzymology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006003:Glycogen / Q000032:analysis; D006706:Homeostasis; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000201:enzymology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D018482:Muscle, Skeletal / Q000737:chemistry / Q000201:enzymology*; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology*; D009765:Obesity / Q000378:metabolism*; D010084:Oxidation-Reduction; D011768:Pyruvate Dehydrogenase Complex / Q000032:analysis / Q000378:metabolism*; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D004852:Epoxy Compounds; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D007328:Insulin; D011768:Pyruvate Dehydrogenase Complex; D006003:Glycogen; D002334:Carnitine O-Palmitoyltransferase; D005947:Glucose; C054207:etomoxir