Acute liver carnitine palmitoyltransferase I overexpression recapitulates reduced palmitate oxidation of cardiac hypertrophy

Circ Res. 2013 Jan 4;112(1):57-65. doi: 10.1161/CIRCRESAHA.112.274456. Epub 2012 Sep 14.


Rationale: Muscle carnitine palmitoyltransferase I is predominant in the heart, but the liver isoform (liver carnitine palmitoyltransferase I [L-CPT1]) is elevated in hearts with low long chain fatty acid oxidation, such as fetal and hypertrophied hearts.

Objective: This work examined the effect of acute L-CPT1 expression on the regulation of palmitate oxidation and energy metabolism in intact functioning rat hearts for comparison with 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) vs. phosphate-buffered saline (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 muscle carnitine palmitoyltransferase I was unaffected. Despite similar tricarboxylic acid cycle rates, palmitate oxidation rates were reduced with L-CPT1 (1.12 ± 0.29 μmol/min per gram of dry weight, 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 nondiseased adult heart, recapitulating the phenotype of reduced long chain fatty acid 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 long chain fatty acid oxidation via L-CPT1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetyl-CoA Carboxylase / metabolism
  • Animals
  • Atrial Natriuretic Factor / genetics
  • Atrial Natriuretic Factor / metabolism
  • Carboxy-Lyases / metabolism
  • Cardiomegaly / enzymology*
  • Cardiomegaly / genetics
  • Carnitine O-Palmitoyltransferase / genetics
  • Carnitine O-Palmitoyltransferase / metabolism*
  • Disease Models, Animal
  • Energy Metabolism*
  • Gene Expression Regulation, Enzymologic
  • Gene Transfer Techniques
  • Genotype
  • Liver / enzymology*
  • Magnetic Resonance Spectroscopy
  • Male
  • Malonyl Coenzyme A / metabolism
  • Myocardium / enzymology*
  • Oxidation-Reduction
  • Palmitic Acid / metabolism*
  • Phenotype
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Up-Regulation


  • RNA, Messenger
  • Palmitic Acid
  • Malonyl Coenzyme A
  • Atrial Natriuretic Factor
  • Carnitine O-Palmitoyltransferase
  • Carboxy-Lyases
  • malonyl-CoA decarboxylase
  • Acetyl-CoA Carboxylase