title: Mouse strain-specific differences in cardiac metabolic enzyme activities observed in a model of isoproterenol-induced cardiac hypertrophy.
abstract: 1. Alterations in myocardial energy metabolism accompany pressure overload-induced hypertrophy. We previously described a novel model of catecholamine-induced hypertrophy in which A/J mice exhibit more robust cardiac hypertrophy than B6 mice. Accordingly, we assessed the influence of mouse strain on the activities of key myocardial metabolic enzymes and whether there are strain-related metabolic adaptations to short-term, high-dose isoproterenol (ISO) administration. 2. Thirty-nine male mice (19 A/J mice, 20 B6 mice), aged 12-15 weeks, were randomly assigned to receive either ISO (100 mg/kg, s.c.) or vehicle (sterile water) daily for 5 days. On Day 6, all hearts were excised, weighed, freeze clamped and assayed for pyruvate dehydrogenase (PDH), medium chain acyl-CoA dehydrogenase, carnitine palmitoyl transferase I and citrate synthase activities. Plasma fatty acids (FA) were also measured. 3. The ISO-treated A/J mice demonstrated greater percentage increases in gravimetric heart weight/bodyweight ratio than ISO-treated B6 mice (24 vs 3%, respectively; P < 0.001). All enzyme activities were significantly greater in vehicle-treated B6 mice than in A/J mice, illustrating a greater capacity for aerobic metabolism in B6 mice. Administration of ISO reduced PDHa (active form) activity in B6 mice by 47% (P < 0.001), with no significant change seen in A/J mice. Free FA levels were not significantly different between groups; thus, the differences in PDHa were not due to changes in FA. 4. The basal activity of myocardial metabolic enzymes is greater in B6 mice than in A/J mice and ISO alters myocardial PDH activity in a mouse strain-dependent manner. Compared with A/J mice, B6 mice demonstrate less ISO-induced cardiac hypertrophy, but greater activity of key enzymes regulating FA and carbohydrate oxidation, which may protect against the development of hypertrophy. The metabolic adaptations associated with ISO-induced hypertrophy differ from those reported with pressure overload hypertrophy.
authors.affiliation: Department of Medicine, Division of Cardiology, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, Ohio 44106-5038, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Faulx
authors.forename: Margaret P
authors.initials: MP
authors.lastname: Chandler
authors.forename: Michael S
authors.initials: MS
authors.lastname: Zawaneh
authors.forename: William C
authors.initials: WC
authors.lastname: Stanley
authors.forename: Brian D
authors.initials: BD
authors.lastname: Hoit
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000378:metabolism; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000378:metabolism*; D007545:Isoproterenol; D007658:Ketone Oxidoreductases / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000201:enzymology*; D013045:Species Specificity
chemical_list: D007658:Ketone Oxidoreductases; D042964:Acyl-CoA Dehydrogenase; D002334:Carnitine O-Palmitoyltransferase; D002950:Citrate (si)-Synthase; D007545:Isoproterenol