Inhibition of carnitine palmitoyltransferase-1 activity alleviates insulin resistance in diet-induced obese mice

Diabetes

Volumn 62, Issue 3, 2013, Pages 711-720

  Keung, Wendy ^a   Ussher, John R ^a   Jaswal, Jagdip S ^a   Raubenheimer, Monique ^a   Lam, Victoria H M ^a   Wagg, Cory S ^a   Lopaschuk, Gary D ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

CARBOHYDRATE; CARNITINE PALMITOYLTRANSFERASE I; CERAMIDE; DIACYLGLYCEROL; FATTY ACID; GLUCOSE TRANSPORTER 4; LONG CHAIN FATTY ACID COENZYME A LIGASE; OXFENICINE; PROTEIN KINASE B; PYRUVATE DEHYDROGENASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME INHIBITION; FATTY ACID TRANSPORT; GASTROCNEMIUS MUSCLE; GLUCOSE TOLERANCE; INSULIN RESISTANCE; INSULIN SENSITIVITY; LUNG GAS EXCHANGE; MALE; MOUSE; NONHUMAN; OBESITY; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION;

ANIMALS; ANTI-OBESITY AGENTS; CARBOHYDRATE METABOLISM; CARNITINE O-PALMITOYLTRANSFERASE; CELL MEMBRANE; DIET, HIGH-FAT; ENZYME INHIBITORS; GLUCOSE INTOLERANCE; GLUCOSE TRANSPORTER TYPE 4; GLYCINE; INSULIN RESISTANCE; LIPID METABOLISM; MALE; MICE; MICE, INBRED C57BL; MITOCHONDRIA, MUSCLE; MUSCLE, SKELETAL; OBESITY; RANDOM ALLOCATION; SIGNAL TRANSDUCTION;

EID: 84874409527     PISSN: 00121797     EISSN: 1939327X     Source Type: Journal    
DOI: 10.2337/db12-0259     Document Type: Article

References (56)

1. Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults, 1999-2000. JAMA 2002;288:1723-1727
2. Kopelman PG. Obesity as a medical problem. Nature 2000;404:635-643
3. DeFronzo RA, Jacot E, Jequier E, Maeder E, Wahren J, Felber JP. The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes 1981;30:1000-1007
4. Zhang L, Keung W, Samokhvalov V, Wang W, Lopaschuk GD. Role of fatty acid uptake and fatty acid beta-oxidation in mediating insulin resistance in heart and skeletal muscle. Biochim Biophys Acta 2010;1801:1-22
5. Krssak M, Falk Petersen K, Dresner A, et al. Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: A 1H NMR spectroscopy study. Diabetologia 1999;42:113-116
6. Itani SI, Ruderman NB, Schmieder F, Boden G. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha. Diabetes 2002;51:2005-2011
7. Ussher JR, Koves TR, Cadete VJ, et al. Inhibition of de novo ceramide synthesis reverses diet-induced insulin resistance and enhances wholebody oxygen consumption. Diabetes 2010;59:2453-2464
8. Holland WL, Brozinick JT, Wang LP, et al. Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance. Cell Metab 2007;5:167-179
9. Thompson AL, Cooney GJ. Acyl-CoA inhibition of hexokinase in rat and human skeletal muscle is a potential mechanism of lipid-induced insulin resistance. Diabetes 2000;49:1761-1765
10. Abu-Elheiga L, Oh W, Kordari P, Wakil SJ. Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by highfat/high- carbohydrate diets. Proc Natl Acad Sci U S A 2003;100:10207-10212
11. Bruce CR, Hoy AJ, Turner N, et al. Overexpression of carnitine palmitoyltransferase-1 in skeletal muscle is sufficient to enhance fatty acid oxidation and improve high-fat diet-induced insulin resistance. Diabetes 2009;58:550-558
12. Fisher JS, Gao J, Han DH, Holloszy JO, Nolte LA. Activation of AMP kinase enhances sensitivity of muscle glucose transport to insulin. Am J Physiol Endocrinol Metab 2002;282:E18-E23
13. Hancock CR, Han DH, Chen M, et al. High-fat diets cause insulin resistance despite an increase in muscle mitochondria. Proc Natl Acad Sci U S A 2008;105:7815-7820
14. Turner N, Bruce CR, Beale SM, et al. Excess lipid availability increases mitochondrial fatty acid oxidative capacity in muscle: Evidence against a role for reduced fatty acid oxidation in lipid-induced insulin resistance in rodents. Diabetes 2007;56:2085-2092
15. Koves TR, Li P, An J, et al. Peroxisome proliferator-activated receptorgamma co-activator 1alpha-mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid-induced mitochondrial inefficiency. J Biol Chem 2005;280:33588-33598
16. Koves TR, Ussher JR, Noland RC, et al. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab 2008;7:45-56
17. Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1963;1:785-789
18. Roden M, Price TB, Perseghin G, et al. Mechanism of free fatty acidinduced insulin resistance in humans. J Clin Invest 1996;97:2859-2865
19. Kerner J, Hoppel C. Fatty acid import into mitochondria. Biochim Biophys Acta 2000;1486:1-17
20. McGarry JD, Brown NF. The mitochondrial carnitine palmitoyltransferase system. From concept to molecular analysis. Eur J Biochem 1997;244: 1-14
21. Ussher JR, Lopaschuk GD. The malonyl CoA axis as a potential target for treating ischaemic heart disease. Cardiovasc Res 2008;79:259-268
22. Nyman LR, Cox KB, Hoppel CL, et al. Homozygous carnitine palmitoyltransferase 1a (liver isoform) deficiency is lethal in the mouse. Mol Genet Metab 2005;86:179-187
23. Ji S, You Y, Kerner J, et al. Homozygous carnitine palmitoyltransferase 1b (muscle isoform) deficiency is lethal in the mouse. Mol Genet Metab 2008; 93:314-322
24. Higgins AJ, Morville M, Burges RA, Blackburn KJ. Mechanism of action of oxfenicine on muscle metabolism. Biochem Biophys Res Commun 1981; 100:291-296
25. Stephens TW, Higgins AJ, Cook GA, Harris RA. Two mechanisms produce tissue-specific inhibition of fatty acid oxidation by oxfenicine. Biochem J 1985;227:651-660
26. Ceccarelli SM, Chomienne O, Gubler M, Arduini A. Carnitine palmitoyltransferase (CPT) modulators: A medicinal chemistry perspective on 35 years of research. J Med Chem 2011;54:3109-3152
27. Lopaschuk GD, Witters LA, Itoi T, Barr R, Barr A. Acetyl-CoA carboxylase involvement in the rapid maturation of fatty acid oxidation in the newborn rabbit heart. J Biol Chem 1994;269:25871-25878
28. Riedel MJ, Baczkó I, Searle GJ, et al. Metabolic regulation of sodiumcalcium exchange by intracellular acyl CoAs. EMBO J 2006;25:4605-4614
29. Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 1957;226:497-509
30. Preiss J, Loomis CR, Bishop WR, Stein R, Niedel JE, Bell RM. Quantitative measurement of sn-1,2-diacylglycerols present in platelets, hepatocytes, and ras-and sis-transformed normal rat kidney cells. J Biol Chem 1986; 261:8597-8600
31. Constantin-Teodosiu D, Cederblad G, Hultman E. A sensitive radioisotopic assay of pyruvate dehydrogenase complex in human muscle tissue. Anal Biochem 1991;198:347-351
32. Jaswal JS, Lund CR, Keung W, Beker DL, Rebeyka IM, Lopaschuk GD. Isoproterenol stimulates 59-AMP-activated protein kinase and fatty acid oxidation in neonatal hearts. Am J Physiol Heart Circ Physiol 2010;299: H1135-H1145
33. Glatz JF, Bonen A, Ouwens DM, Luiken JJ. Regulation of sarcolemmal transport of substrates in the healthy and diseased heart. Cardiovasc Drugs Ther 2006;20:471-476
34. Iglesias MA, Ye JM, Frangioudakis G, et al. AICAR administration causes an apparent enhancement of muscle and liver insulin action in insulinresistant high-fat-fed rats. Diabetes 2002;51:2886-2894
35. Wolfe RR. Metabolic interactions between glucose and fatty acids in humans. Am J Clin Nutr 1998;67(Suppl.):519S-526S
36. Bachmann E, Weber E. Biochemical mechanisms of oxfenicine cardiotoxicity. Pharmacology 1988;36:238-248
37. Greaves P, Martin J, Michel MC, Mompon P. Cardiac hypertrophy in the dog and rat induced by oxfenicine, an agent which modifies muscle metabolism. Arch Toxicol Suppl 1984;7:488-493
38. Okere IC, Chandler MP, McElfresh TA, et al. Carnitine palmitoyl transferase-I inhibition is not associated with cardiac hypertrophy in rats fed a high-fat diet. Clin Exp Pharmacol Physiol 2007;34:113-119
39. Ussher JR, Koves TR, Jaswal JS, et al. Insulin-stimulated cardiac glucose oxidation is increased in high-fat diet-induced obese mice lacking malonyl CoA decarboxylase. Diabetes 2009;58:1766-1775
40. Lopaschuk GD, Ussher JR, Folmes CD, Jaswal JS, Stanley WC. Myocardial fatty acid metabolism in health and disease. Physiol Rev 2010;90:207-258
41. Hoehn KL, Turner N, Swarbrick MM, et al. Acute or chronic upregulation of mitochondrial fatty acid oxidation has no net effect on whole-body energy expenditure or adiposity. Cell Metab 2010;11:70-76
42. Keung W, Palaniyappan A, Lopaschuk GD. Chronic central leptin decreases food intake and improves glucose tolerance in diet-induced obese mice independent of hypothalamic malonyl CoA levels and skeletal muscle insulin sensitivity. Endocrinology 2011;152:4127-4137
43. Hübinger A, Knode O, Susanto F, Reinauer H, Gries FA. Effects of the carnitine-acyltransferase inhibitor etomoxir on insulin sensitivity, energy expenditure and substrate oxidation in NIDDM. Horm Metab Res 1997;29:436-439
44. Ratheiser K, Schneeweiss B, Waldhäusl W, et al. Inhibition by etomoxir of carnitine palmitoyltransferase I reduces hepatic glucose production and plasma lipids in non-insulin-dependent diabetes mellitus. Metabolism 1991; 40:1185-1190
45. Deems RO, Anderson RC, Foley JE. Hypoglycemic effects of a novel fatty acid oxidation inhibitor in rats and monkeys. Am J Physiol 1998;274:R524-R528
46. Spurway TD, Pogson CI, Sherratt HS, Agius L. Etomoxir, sodium 2-[6-(4-chlorophenoxy)hexyl] oxirane-2-carboxylate, inhibits triacylglycerol depletion in hepatocytes and lipolysis in adipocytes. FEBS Lett 1997;404: 111-114
47. Horn CC, Ji H, Friedman MI. Etomoxir, a fatty acid oxidation inhibitor, increases food intake and reduces hepatic energy status in rats. Physiol Behav 2004;81:157-162
48. Finck BN, Bernal-Mizrachi C, Han DH, et al. A potential link between muscle peroxisome proliferator-activated receptor-alpha signaling and obesity-related diabetes. Cell Metab 2005;1:133-144
49. Li X, Monks B, Ge Q, Birnbaum MJ. Akt/PKB regulates hepatic metabolism by directly inhibiting PGC-1alpha transcription coactivator. Nature 2007; 447:1012-1016
50. Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature 2005;434:113-118
51. Park SY, Kim HJ, Wang S, et al. Hormone-sensitive lipase knockout mice have increased hepatic insulin sensitivity and are protected from shortterm diet-induced insulin resistance in skeletal muscle and heart. Am J Physiol Endocrinol Metab 2005;289:E30-E39
52. Dobbins RL, Szczepaniak LS, Bentley B, Esser V, Myhill J, McGarry JD. Prolonged inhibition of muscle carnitine palmitoyltransferase-1 promotes intramyocellular lipid accumulation and insulin resistance in rats. Diabetes 2001;50:123-130
53. Luiken JJ, Niessen HE, Coort SL, et al. Etomoxir-induced partial carnitine palmitoyltransferase-I (CPT-I) inhibition in vivo does not alter cardiac long-chain fatty acid uptake and oxidation rates. Biochem J 2009;419:447-455
54. Eaton S. Control of mitochondrial beta-oxidation flux. Prog Lipid Res 2002; 41:197-239
55. Furler SM, Cooney GJ, Hegarty BD, Lim-Fraser MY, Kraegen EW, Oakes ND. Local factors modulate tissue-specific NEFA utilization: Assessment in rats using 3H-(R)-2-bromopalmitate. Diabetes 2000;49:1427-1433
56. Yu C, Chen Y, Cline GW, et al. Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem 2002;277:50230-50236