An acute increase in skeletal muscle carnitine content alters fuel metabolism in resting human skeletal muscle.
BACKGROUND
Carnitine plays an essential role in the integration of fat and carbohydrate oxidation in skeletal muscle, which is impaired in obesity and type 2 diabetes.


OBJECTIVE
The aim of the present study was to investigate the effect of an increase in skeletal muscle total carnitine (TC) content on muscle fuel metabolism.


METHODS
A 5-h iv infusion of saline (control) or l-carnitine was administered while serum insulin was maintained at a physiologically high concentration during two randomized visits.


METHODS
Seven healthy, nonvegetarian young men (body mass index, 26.1 +/- 1.6 kg/m2) participated in the present study at the University of Nottingham.


METHODS
Skeletal muscle pyruvate dehydrogenase complex (PDC) activity and associated muscle metabolites were measured.


RESULTS
The combination of hypercarnitinemia (600 micromol/liter) and hyperinsulinemia (160 mU/liter) increased muscle TC content by 15% (P < 0.01) and was associated with decreased pyruvate dehydrogenase complex activity (P < 0.05) and muscle lactate content (P < 0.05) by 30 and 40%, respectively, and an overnight increase in muscle glycogen (P < 0.01) and long-chain acyl-coenzyme A content (P < 0.05) by 30 and 40%, respectively, compared with control.


CONCLUSIONS
These results suggest that an acute increase in human skeletal muscle TC content results in an inhibition of carbohydrate oxidation in conditions of high carbohydrate availability, possibly due to a carnitine-mediated increase in fat oxidation. These novel findings may have important implications for our understanding of the regulation of muscle fat oxidation, particularly during exercise, when carnitine availability may limit fat oxidation, and in obesity and type 2 diabetes where it is known to be impaired.
Stephens
Francis B
FB
Centre for Integrated Systems Biology and Medicine, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom. francis.stephens@nottingham.ac.uk
Constantin-Teodosiu
Dumitru
D
Laithwaite
David
D
Simpson
Elizabeth J
EJ
Greenhaff
Paul L
PL
D000214:Acyl Coenzyme A / Q000032:analysis / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002331:Carnitine / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects*; D005215:Fasting / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000008:administration & dosage / Q000493:pharmacokinetics; D019298:Glucose-6-Phosphate / Q000032:analysis / Q000378:metabolism; D006003:Glycogen / Q000032:analysis; D006801:Humans; D007260:Infusion Pumps; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D019344:Lactic Acid / Q000032:analysis / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D012146:Rest / Q000502:physiology*
D000214:Acyl Coenzyme A; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D011768:Pyruvate Dehydrogenase Complex; D019344:Lactic Acid; D019298:Glucose-6-Phosphate; D006003:Glycogen; D005947:Glucose; D002331:Carnitine