TitleAcetyl-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.
Publication TypeJournal Article
Year of Publication2012
AuthorsGómez LA, Heath S-HD, Hagen TM
JournalMech Ageing Dev
Volume133
Issue2-3
Pagination99-106
Date Published2012 Feb-Mar
ISSN1872-6216
KeywordsAcetylcarnitine, Age Factors, Animals, Carnitine, Carnitine O-Palmitoyltransferase, Dietary Supplements, Kinetics, Male, Mitochondria, Mitochondria, Heart, Models, Biological, Myocardium, Palmitoyl Coenzyme A, Rats, Rats, Inbred F344
Abstract

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.

DOI10.1016/j.mad.2012.01.007
Alternate JournalMech. Ageing Dev.
PubMed ID22322067
PubMed Central IDPMC4147858
Grant ListR01 AG017141 / AG / NIA NIH HHS / United States
P01AT002034 / AT / NCCIH NIH HHS / United States
2R01AG017141-06A2 / AG / NIA NIH HHS / United States
ES00240 / ES / NIEHS NIH HHS / United States
P01 AT002034 / AT / NCCIH NIH HHS / United States