Acetyl-L-carnitine supplementation reverses the age-related decline in carnitine palmitoyltransferase 1 (CPT1) activity in interfibrillar mitochondria without changing the L-carnitine content in the rat heart

Mech Ageing Dev. Feb-Mar 2012;133(2-3):99-106. doi: 10.1016/j.mad.2012.01.007. Epub 2012 Feb 1.


The aging heart displays a loss of bioenergetic reserve capacity partially mediated through lower fatty acid utilization. We investigated whether the age-related impairment of cardiac fatty acid catabolism occurs, at least partially, through diminished levels of L-carnitine, which would adversely affect carnitine palmitoyltransferase 1 (CPT1), the rate-limiting enzyme for fatty acyl-CoA uptake into mitochondria for β-oxidation. Old (24-28 mos) Fischer 344 rats were fed±acetyl-L-carnitine (ALCAR; 1.5% [w/v]) for up to four weeks prior to sacrifice and isolation of cardiac interfibrillar (IFM) and subsarcolemmal (SSM) mitochondria. IFM displayed a 28% (p<0.05) age-related loss of CPT1 activity, which correlated with a decline (41%, p<0.05) in palmitoyl-CoA-driven state 3 respiration. Interestingly, SSM had preserved enzyme function and efficiently utilized palmitate. Analysis of IFM CPT1 kinetics showed both diminished V(max) and K(m) (60% and 49% respectively, p<0.05) when palmitoyl-CoA was the substrate. However, no age-related changes in enzyme kinetics were evident with respect to L-carnitine. ALCAR supplementation restored CPT1 activity in heart IFM, but not apparently through remediation of L-carnitine levels. Rather, ALCAR influenced enzyme activity over time, potentially by modulating conditions in the aging heart that ultimately affect palmitoyl-CoA binding and CPT1 kinetics.

Publication types

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

MeSH terms

  • Acetylcarnitine / metabolism*
  • Age Factors
  • Animals
  • Carnitine / metabolism*
  • Carnitine O-Palmitoyltransferase / genetics*
  • Carnitine O-Palmitoyltransferase / metabolism*
  • Dietary Supplements*
  • Kinetics
  • Male
  • Mitochondria / metabolism
  • Mitochondria, Heart / metabolism
  • Models, Biological
  • Myocardium / metabolism*
  • Palmitoyl Coenzyme A / metabolism
  • Rats
  • Rats, Inbred F344


  • Palmitoyl Coenzyme A
  • Acetylcarnitine
  • Carnitine O-Palmitoyltransferase
  • Carnitine