Acute Liver Carnitine Palmitoyltransferase I Overexpression Recapitulates Reduced Palmitate Oxidation of Cardiac Hypertrophy

作者：Lewandowski E Douglas^*; Fischer Susan K; Fasano Matthew; Banke Natasha H; Walker Lori A; Huqi Alda; Wang Xuerong; Lopaschuk Gary D; O'Donnell J Michael

来源：Circulation Research, 2013, 112(1): 57-+.

DOI：10.1161/CIRCRESAHA.112.274456

• beta-oxidation
• hypertrophy
• long chain fatty acids
• mitochondria
• palmitoyltransferase I

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 mu mol/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. (Circ Res. 2013;112:57-65.)

• 出版日期2013-1-4