The effect of body weight and the fatty acid-oxidation inhibitor 2-tetradecylglycidic acid on pyruvate dehydrogenase complex activity in mouse heart.
The proportion of pyruvate dehydrogenase complex in the active, dephosphorylated form was decreased (compared with lean controls) in heart muscle in gold thioglucose-treated obese hyperinsulinaemic mice, and the extent of enzyme inactivation was significantly linearly correlated with both body weight and body fat content. A single oral dose (25 mg/kg body wt.) of the beta-oxidation inhibitor 2-tetradecylglycidic acid to obese animals restored pyruvate dehydrogenase complex activity to that of lean controls. It is suggested that increased fatty acid oxidation may be a major factor in mediating the phosphorylation and inactivation of pyruvate dehydrogenase complex in mouse heart muscle in obesity, and this may represent an important mechanism in the development and/or expression of insulin resistance in respect of abnormalities of cellular glucose homoeostasis in these animals.
D000273:Adipose Tissue / Q000033:anatomy & histology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D004852:Epoxy Compounds / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009206:Myocardium / Q000201:enzymology*; D009765:Obesity / Q000201:enzymology*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*
D001786:Blood Glucose; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D005227:Fatty Acids; D007328:Insulin; D011768:Pyruvate Dehydrogenase Complex; C021756:2-tetradecylglycidic acid