Carnitine revisited: potential use as adjunctive treatment in diabetes.
OBJECTIVE
This study examined the efficacy of supplemental L: -carnitine as an adjunctive diabetes therapy in mouse models of metabolic disease. We hypothesised that carnitine would facilitate fatty acid export from tissues in the form of acyl-carnitines, thereby alleviating lipid-induced insulin resistance.


METHODS
Obese mice with genetic or diet-induced forms of insulin resistance were fed rodent chow +/- 0.5% L: -carnitine for a period of 1-8 weeks. Metabolic outcomes included insulin tolerance tests, indirect calorimetry and mass spectrometry-based profiling of acyl-carnitine esters in tissues and plasma.


RESULTS
Carnitine supplementation improved insulin-stimulated glucose disposal in genetically diabetic mice and wild-type mice fed a high-fat diet, without altering body weight or food intake. In severely diabetic mice, carnitine supplementation increased average daily respiratory exchange ratio from 0.886 +/- 0.01 to 0.914 +/- 0.01 (p < 0.01), reflecting a marked increase in systemic carbohydrate oxidation. Similarly, under insulin-stimulated conditions, carbohydrate oxidation was higher and total energy expenditure increased from 172 +/- 10 to 210 +/- 9 kJ kg fat-free mass(-1) h(-1) in the carnitine-supplemented compared with control animals. These metabolic improvements corresponded with a 2.3-fold rise in circulating levels of acetyl-carnitine, which accounts for 86 and 88% of the total acyl-carnitine pool in plasma and skeletal muscle, respectively. Carnitine supplementation also increased several medium- and long-chain acyl-carnitine species in both plasma and tissues.


CONCLUSIONS
These findings suggest that carnitine supplementation relieves lipid overload and glucose intolerance in obese rodents by enhancing mitochondrial efflux of excess acyl groups from insulin-responsive tissues. Carefully controlled clinical trials should be considered.
Power
R A
RA
Division of Nutrition and Chronic Disease, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
Hulver
M W
MW
Zhang
J Y
JY
Dubois
J
J
Marchand
R M
RM
Ilkayeva
O
O
Muoio
D M
DM
Mynatt
R L
RL
D000818:Animals; D002151:Calorimetry / Q000379:methods; D002331:Carnitine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000188:drug therapy*; D005227:Fatty Acids / Q000378:metabolism; D005951:Glucose Tolerance Test; D005990:Glycerol / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008820:Mice, Obese; D030481:Pyruvate Dehydrogenase (Lipoamide) / Q000378:metabolism; D014803:Vitamin B Complex / Q000627:therapeutic use
D005227:Fatty Acids; C116917:acylcarnitine; D014803:Vitamin B Complex; D030481:Pyruvate Dehydrogenase (Lipoamide); D005990:Glycerol; D002331:Carnitine