Acute L-CPT1 Overexpression Recapitulates Reduced Palmitate Oxidation of Cardiac Hypertrophy
Rationale: Muscle carnitine palmitoyltransferase I (M-CPT1) is predominant in heart, but the liver isoform (L-CPT1) is elevated in hearts with low long chain fatty acid (LCFA) oxidation, such as fetal and hypertrophied hearts.
Objective: This work examined the effect of acute L-CPT1 expression has on the regulation of palmitate oxidation and energy metabolism in intact functioning rat hearts for comparison to findings in hypertrophied hearts.
Methods and Results: L-CPT1 was expressed in vivo in rat hearts by coronary perfusion of Adv.cmv.L-CPT1 (L-CPT1, n=15) versus PBS infusion (PBS, n=7) or empty virus (EMPTY, n=5). L-CPT1 was elevated 5-fold at 72 hours after Adv.cmv.L-CPT1 infusion (P<0.05), but M-CPT1 was unaffected. Despite similar tricarboxylic acid cycle rates, palmitate oxidation rates were reduced with L-CPT1 (1.12±0.29 micromole/min/g dw, mean±SE) vs PBS (1.6±0.34). Acetyl CoA production from palmitate was reduced with L-CPT1 (69%±0.02, P<0.05; PBS= 79%±0.01, Empty=81%±0.02), similar to what occurs in hypertrophied hearts and with no difference in malonyl CoA content. Glucose oxidation was elevated with L-CPT1 (by 60%). Surprisingly, L-CPT1 hearts contained elevated atrial natriuretic peptide, indicating induction of hypertrophic signaling.
Conclusions: The results link L-CPT1 expression to reduced palmitate oxidation in a non-diseased, adult heart, recapitulating the phenotype of reduced LCFA oxidation in cardiac hypertrophy. The implications are that L-CPT1 expression induces metabolic remodeling hypertrophic signaling, and that regulatory factors beyond malonyl-CoA in the heart regulate LCFA oxidation via L-CPT1.
- Received May 25, 2012.
- Accepted September 14, 2012.
- Copyright © 2012, American Heart Association