Open AccessThe effect of body weight and the fatty acid-oxidation inhibitor 2-tetradecylglycidic acid on pyruvate dehydrogenase complex activity in mouse heart
Author(s) -
Ian D. Caterson,
Paul F. Williams,
A L Kerbey,
L D Astbury,
Walter E. Plehwe,
John R. Turtle
Publication year - 1984
Publication title -
biochemical journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.706
H-Index - 265
eISSN - 1470-8728
pISSN - 0264-6021
DOI - 10.1042/bj2240787
Subject(s) - pyruvate dehydrogenase complex , beta oxidation , medicine , endocrinology , pyruvate decarboxylation , pyruvate dehydrogenase kinase , fatty acid , dehydrogenase , insulin resistance , chemistry , fatty acid synthesis , pyruvate dehydrogenase phosphatase , biology , enzyme , metabolism , biochemistry , insulin
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.