Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Acylcarnitines—old actors auditioning for new roles in metabolic physiology

Nature Reviews Endocrinology volume 11, pages 617–625 (2015)Cite this article

Subjects

Key Points

  • Long-chain acylcarnitines (LCACs) are lipid derivatives generated from carnitine by mitochondrial carnitine O-palmitoyltransferase 1 or through the reversible activity of carnitine O-palmitoyltransferase 2 on long-chain acyl-coenzyme A metabolites

  • Long-chain acyl-coenzyme A metabolites are impermeable to mitochondrial membranes; therefore, LCACs act as the fatty acid transport moieties for oxidative catabolism

  • Mutations in key enzymes increase mitochondrial and cytosolic pools of long-chain acyl-coenzyme A, promoting an accumulation of LCACs that is diagnostic of fatty acid oxidation disorders

  • LCACs can modulate inflammation, insulin sensitivity, myocyte stress, protein kinase C signalling and ion balance, which suggests that they contribute to both physiological and pathophysiological processes beyond fuel trafficking

  • A model is proposed to explain how LCACs affect disparate cell systems on the basis of their zwitterion biochemical structure and published evidence that they interact with plasma membranes

  • In this model, accumulation of LCACs is predicted to alter the activities of key receptors, transporters, channels and enzymes that associate with (or involve) plasma, mitochondrial or other membranes

Abstract

Perturbations in metabolic pathways can cause substantial increases in plasma and tissue concentrations of long-chain acylcarnitines (LCACs). For example, the levels of LCACs and other acylcarnitines rise in the blood and muscle during exercise, as changes in tissue pools of acyl-coenzyme A reflect accelerated fuel flux that is incompletely coupled to mitochondrial energy demand and capacity of the tricarboxylic acid cycle. This natural ebb and flow of acylcarnitine generation and accumulation contrasts with that of inherited fatty acid oxidation disorders (FAODs), cardiac ischaemia or type 2 diabetes mellitus. These conditions are characterized by very high (FAODs, ischaemia) or modestly increased (type 2 diabetes mellitus) tissue and blood levels of LCACs. Although specific plasma concentrations of LCACs and chain-lengths are widely used as diagnostic markers of FAODs, research into the potential effects of excessive LCAC accumulation or the roles of acylcarnitines as physiological modulators of cell metabolism is lacking. Nevertheless, a growing body of evidence has highlighted possible effects of LCACs on disparate aspects of pathophysiology, such as cardiac ischaemia outcomes, insulin sensitivity and inflammation. This Review, therefore, aims to provide a theoretical framework for the potential consequences of tissue build-up of LCACs among individuals with metabolic disorders.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Generation and transport of LCACs under physiological and pathophysiological conditions.
Figure 2: Working model of LCAC modulatory activity.

Similar content being viewed by others

References

  1. Reuter, S. E. & Evans, A. M. Carnitine and acylcarnitines: pharmacokinetic, pharmacological and clinical aspects. Clin. Pharmacokinet. 51, 553–572 (2012).

    Article  CAS  PubMed  Google Scholar 

  2. Rinaldo, P., Matern, D. & Bennett, M. J. Fatty acid oxidation disorders. Annu. Rev. Physiol. 64, 477–502 (2002).

    Article  CAS  PubMed  Google Scholar 

  3. Wilcken, B., Wiley, V., Hammond, J. & Carpenter, K. Screening newborns for inborn errors of metabolism by tandem mass spectrometry. N. Engl. J. Med. 348, 2304–2312 (2003).

    Article  CAS  PubMed  Google Scholar 

  4. Rocha, H. et al. Birth prevalence of fatty acid β-oxidation disorders in Iberia. JIMD Rep. 16, 89–94 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Brass, E. P. & Hoppel, C. L. Relationship between acid-soluble carnitine and coenzyme A pools in vivo. Biochem J. 190, 495–504 (1980).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ramsay, R. R. & Zammit, V. A. Carnitine acyltransferases and their influence on CoA pools in health and disease. Mol. Aspects Med. 25, 475–493 (2004).

    Article  CAS  PubMed  Google Scholar 

  7. Eaton, S., Bartlett, K. & Pourfarzam, M. Mammalian mitochondrial β-oxidation. Biochem J. 320, 345–357 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Noland, R. C. et al. Carnitine insufficiency caused by aging and overnutrition compromises mitochondrial performance and metabolic control. J. Biol. Chem. 284, 22840–22852 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Violante, S. et al. Carnitine palmitoyltransferase 2 and carnitine/acylcarnitine translocase are involved in the mitochondrial synthesis and export of acylcarnitines. FASEB J. 27, 2039–2044 (2013).

    Article  CAS  PubMed  Google Scholar 

  10. Palmieri, F. The mitochondrial transporter family SLC25: identification, properties and physiopathology. Mol. Aspects Med. 34, 465–484 (2013).

    Article  CAS  PubMed  Google Scholar 

  11. Pochini, L., Oppedisano, F. & Indiveri, C. Reconstitution into liposomes and functional characterization of the carnitine transporter from renal cell plasma membrane. Biochim. Biophys. Acta 1661, 78–86 (2004).

    Article  CAS  PubMed  Google Scholar 

  12. Suhre, K. et al. Human metabolic individuality in biomedical and pharmaceutical research. Nature 477, 54–60 (2011).

    Article  CAS  PubMed  Google Scholar 

  13. Hediger, M. A. et al. The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteins. Pflugers Arch. 447, 465–468 (2004).

    Article  CAS  PubMed  Google Scholar 

  14. He, L., Vasiliou, K. & Nebert, D. W. Analysis and update of the human solute carrier (SLC) gene superfamily. Hum. Genomics 3, 195–206 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Carpenter, K. H. & Wiley, V. Application of tandem mass spectrometry to biochemical genetics and newborn screening. Clin. Chim. Acta 322, 1–10 (2002).

    Article  CAS  PubMed  Google Scholar 

  16. Rinaldo, P., Cowan, T. M. & Matern, D. Acylcarnitine profile analysis. Genet. Med. 10, 151–156 (2008).

    Article  PubMed  Google Scholar 

  17. Bonnefont, J. P. et al. Carnitine palmitoyltransferase deficiencies. Mol. Genet. Metab. 68, 424–440 (1999).

    Article  CAS  PubMed  Google Scholar 

  18. Matern, D. & Rinaldo, P. in GeneReviews® (eds Pagon, R. A. et al.) Medium-chain acyl-coenzyme A dehydrogenase deficiency (University of Washington, 1993).

    Google Scholar 

  19. Spiekerkoetter, U. Mitochondrial fatty acid oxidation disorders: clinical presentation of long-chain fatty acid oxidation defects before and after newborn screening. J. Inherit. Metab. Dis. 33, 527–532 (2010).

    Article  CAS  PubMed  Google Scholar 

  20. Stanley, C. A. et al. A deficiency of carnitine–acylcarnitine translocase in the inner mitochondrial membrane. N. Engl. J. Med. 327, 19–23 (1992).

    Article  CAS  PubMed  Google Scholar 

  21. Schiff, M. et al. Molecular and cellular pathology of very-long-chain acyl-CoA dehydrogenase deficiency. Mol. Genet. Metab. 109, 21–27 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Rector, R. S., Payne, R. M. & Ibdah, J. A. Mitochondrial trifunctional protein defects: clinical implications and therapeutic approaches. Adv. Drug Deliv. Rev. 60, 1488–1496 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Isackson, P. J. et al. CPT2 gene mutations resulting in lethal neonatal or severe infantile carnitine palmitoyltransferase II deficiency. Mol. Genet. Metab. 94, 422–427 (2008).

    Article  CAS  PubMed  Google Scholar 

  24. McHugh, D. et al. Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: a worldwide collaborative project. Genet. Med. 13, 230–254 (2011).

    Article  PubMed  Google Scholar 

  25. Pollitt, R. J. Disorders of mitochondrial long-chain fatty acid oxidation. J. Inherit. Metab. Dis. 18, 473–490 (1995).

    Article  CAS  PubMed  Google Scholar 

  26. Gillingham, M. B. et al. Optimal dietary therapy of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Mol. Genet. Metab. 79, 114–123 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Schiff, M., Bénit, P., Jacobs, H. T., Vockley, J. & Rustin, P. Therapies in inborn errors of oxidative metabolism. Trends Endocrinol. Metab. 23, 488–495 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Knabb, M. T., Saffitz, J. E., Corr, P. B. & Sobel, B. E. The dependence of electrophysiological derangements on accumulation of endogenous long-chain acyl carnitine in hypoxic neonatal rat myocytes. Circ. Res. 58, 230–240 (1986).

    Article  CAS  PubMed  Google Scholar 

  29. Sato, T., Kiyosue, T. & Arita, M. Inhibitory effects of palmitoylcarnitine and lysophosphatidylcholine on the sodium current of cardiac ventricular cells. Pflugers Arch. 420, 94–100 (1992).

    Article  CAS  PubMed  Google Scholar 

  30. Aguer, C. et al. Acylcarnitines: potential implications for skeletal muscle insulin resistance. FASEB J. 29, 336–345 (2015).

    Article  CAS  PubMed  Google Scholar 

  31. Rutkowsky, J. M. et al. Acylcarnitines activate proinflammatory signaling pathways. Am. J. Physiol. Endocrinol. Metab. 306, E1378–E1387 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. McCoin, C. S., Knotts, T. A., Ono-Moore, K. D., Oort, P. J. & Adams, S. H. Long-chain acylcarnitines activate cell stress and myokine release in C2C12 myotubes: calcium-dependent and -independent effects. Am. J. Physiol. Endocrinol. Metab. 308, E990–E1000 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Sobiesiak-Mirska, J. & A. Nałecz, K. Palmitoylcarnitine modulates interaction between protein kinase C βII and its receptor RACK1. FEBS J. 273, 1300–1311 (2006).

    Article  CAS  PubMed  Google Scholar 

  34. Lopaschuk, G. D., Ussher, J. R., Folmes, C. D., Jaswal, J. S. & Stanley, W. C. Myocardial fatty acid metabolism in health and disease. Physiol. Rev. 90, 207–258 (2010).

    Article  CAS  PubMed  Google Scholar 

  35. Lopaschuk, G. D., Wall, S. R., Olley, P. M. & Davies, N. J. Etomoxir, a carnitine palmitoyltransferase I inhibitor, protects hearts from fatty acid-induced ischemic injury independent of changes in long chain acylcarnitine. Circ. Res. 63, 1036–1043 (1988).

    Article  CAS  PubMed  Google Scholar 

  36. Heathers, G. P., Yamada, K. A., Kanter, E. M. & Corr, P. B. Long-chain acylcarnitines mediate the hypoxia-induced increase in α1-adrenergic receptors on adult canine myocytes. Circ. Res. 61, 735–746 (1987).

    Article  CAS  PubMed  Google Scholar 

  37. Corr, P. B., Creer, M. H., Yamada, K. A., Saffitz, J. E. & Sobel, B. E. Prophylaxis of early ventricular fibrillation by inhibition of acylcarnitine accumulation. J. Clin. Invest. 83, 927–936 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Cho, K. S. & Proulx, P. Lysis of erythrocytes by long-chain acyl esters of carnitine. Biochim. Biophys. Acta 193, 30–35 (1969).

    Article  CAS  PubMed  Google Scholar 

  39. Busselen, P., Sercu, D. & Verdonck, F. Exogenous palmitoyl carnitine and membrane damage in rat hearts. J. Mol. Cell. Cardiol. 20, 905–916 (1988).

    Article  CAS  PubMed  Google Scholar 

  40. Xiao, C. Y., Chen, M., Hara, A., Hashizume, H. & Abiko, Y. Palmitoyl-L-carnitine modifies the myocardial levels of high-energy phosphates and free fatty acids. Basic Res. Cardiol. 92, 320–330 (1997).

    Article  CAS  PubMed  Google Scholar 

  41. Adams, R. J. et al. In vitro effects of palmitylcarnitine on cardiac plasma membrane Na, K-ATPase, and sarcoplasmic reticulum Ca2+-ATPase and Ca2+ transport. J. Biol. Chem. 254, 12404–12410 (1979).

    Article  CAS  PubMed  Google Scholar 

  42. Wu, J. & Corr, P. B. Palmitoylcarnitine increases [Na+]i and initiates transient inward current in adult ventricular myocytes. Am. J. Physiol. 268, H2405–H2417 (1995).

    CAS  PubMed  Google Scholar 

  43. Meszaros, J. & Pappano, A. J. Electrophysiological effects of L-palmitoylcarnitine in single ventricular myocytes. Am. J. Physiol. 258, H931–H938 (1990).

    CAS  PubMed  Google Scholar 

  44. Lamers, J. M., Stinis, H. T., Montfoort, A. & Hulsmann, W. C. The effect of lipid intermediates on Ca2+ and Na+ permeability and (Na+ + K+)-ATPase of cardiac sarcolemma. A possible role in myocardial ischemia. Biochim. Biophys. Acta 774, 127–137 (1984).

    Article  CAS  PubMed  Google Scholar 

  45. Yamada, K. A., Kanter, E. M. & Newatia, A. Long-chain acylcarnitine induces Ca2+ efflux from the sarcoplasmic reticulum. J. Cardiovasc. Pharmacol. 36, 14–21 (2000).

    Article  CAS  PubMed  Google Scholar 

  46. Wood, J. M., Bush, B., Pitts, B. J. & Schwartz, A. Inhibition of bovine heart Na+, K+-ATPase by palmitylcarnitine and palmityl-CoA. Biochem. Biophys. Res. Commun. 74, 677–684 (1977).

    Article  CAS  PubMed  Google Scholar 

  47. el-Hayek, R., Valdivia, C., Valdivia, H. H., Hogan, K. & Coronado, R. Activation of the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum by palmitoyl carnitine. Biophys. J. 65, 779–789 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Wu, J., McHowat, J., Saffitz, J. E., Yamada, K. A. & Corr, P. B. Inhibition of gap junctional conductance by long-chain acylcarnitines and their preferential accumulation in junctional sarcolemma during hypoxia. Circ. Res. 72, 879–889 (1993).

    Article  CAS  PubMed  Google Scholar 

  49. Sato, T., Arita, M. & Kiyosue, T. Differential mechanism of block of palmitoyl lysophosphatidylcholine and of palmitoylcarnitine on inward rectifier K+ channels of guinea-pig ventricular myocytes. Cardiovasc. Drugs Ther. 7 (Suppl. 3), 575–584 (1993).

    Article  PubMed  Google Scholar 

  50. Ferro, F. et al. Long-chain acylcarnitines regulate the hERG channel. PLoS ONE 7, e41686 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Liu, Q. Y. & Rosenberg, R. L. Activation and inhibition of reconstituted cardiac L-type calcium channels by palmitoyl-L-carnitine. Biochem. Biophys. Res. Commun. 228, 252–258 (1996).

    Article  CAS  PubMed  Google Scholar 

  52. Wu, J. & Corr, P. B. Influence of long-chain acylcarnitines on voltage-dependent calcium current in adult ventricular myocytes. Am. J. Physiol. 263, H410–H417 (1992).

    CAS  PubMed  Google Scholar 

  53. De Villiers, M. & Lochner, A. Mitochondrial Ca2+ fluxes: role of free fatty acids, acyl-CoA and acylcarnitine. Biochim Biophys Acta 876, 309–317 (1986).

    Article  CAS  PubMed  Google Scholar 

  54. Wolkowicz, P. E. & McMillin-Wood, J. Respiration-dependent calcium ion uptake by two preparations of cardiac mitochondria. Effects of palmitoyl-coenzyme A and palmitoylcarnitine on calcium ion cycling and nicotinamide nucleotide reduction state. Biochem. J. 186, 257–266 (1980).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Baydoun, A. R., Markham, A., Morgan, R. M. & Sweetman, A. J. Palmitoyl carnitine: an endogenous promotor of calcium efflux from rat heart mitochondria. Biochem Pharmacol 37, 3103–3107 (1988).

    Article  CAS  PubMed  Google Scholar 

  56. Hoppel, C. L. & Genuth, S. M. Carnitine metabolism in normal-weight and obese human subjects during fasting. Am. J. Physiol. 238, E409–E415 (1980).

    CAS  PubMed  Google Scholar 

  57. Adams, S. H. et al. Plasma acylcarnitine profiles suggest incomplete long-chain fatty acid β-oxidation and altered tricarboxylic acid cycle activity in type 2 diabetic African-American women. J. Nutr. 139, 1073–1081 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Mai, M. et al. Serum levels of acylcarnitines are altered in prediabetic conditions. PLoS ONE 8, e82459 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Ha, C. Y. et al. The association of specific metabolites of lipid metabolism with markers of oxidative stress, inflammation and arterial stiffness in men with newly diagnosed type 2 diabetes. Clin. Endocrinol. (Oxf.) 76, 674–682 (2012).

    Article  CAS  Google Scholar 

  60. Mihalik, S. J. et al. Increased levels of plasma acylcarnitines in obesity and type 2 diabetes and identification of a marker of glucolipotoxicity. Obesity (Silver Spring) 18, 1695–1700 (2010).

    Article  CAS  Google Scholar 

  61. Koves, T. R. et al. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab. 7, 45–56 (2008).

    Article  CAS  PubMed  Google Scholar 

  62. Muoio, D. M. & Koves, T. R. Lipid-induced metabolic dysfunction in skeletal muscle. Novartis Found Symp. 286, 24–38 (2007).

    Article  CAS  PubMed  Google Scholar 

  63. Itani, S. I., Ruderman, N. B., Schmieder, F. & Boden, G. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IκB-α. Diabetes 51, 2005–2011 (2002).

    Article  CAS  PubMed  Google Scholar 

  64. Holland, W. L. et al. Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance. Cell Metab. 5, 167–179 (2007).

    Article  CAS  PubMed  Google Scholar 

  65. Hotamisligil, G. S., Shargill, N. S. & Spiegelman, B. M. Adipose expression of tumor necrosis factor-α: direct role in obesity-linked insulin resistance. Science 259, 87–91 (1993).

    Article  CAS  PubMed  Google Scholar 

  66. An, J. et al. Hepatic expression of malonyl-CoA decarboxylase reverses muscle, liver and whole-animal insulin resistance. Nat. Med. 10, 268–274 (2004).

    Article  CAS  PubMed  Google Scholar 

  67. Koves, T. R. et al. Peroxisome proliferator-activated receptor-γ co-activator 1α-mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid-induced mitochondrial inefficiency. J. Biol. Chem. 280, 33588–33598 (2005).

    Article  CAS  PubMed  Google Scholar 

  68. Chao, L. C. et al. Insulin resistance and altered systemic glucose metabolism in mice lacking Nur77. Diabetes 58, 2788–2796 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. De Vogel-van den Bosch, J. et al. The effects of long- or medium-chain fat diets on glucose tolerance and myocellular content of lipid intermediates in rats. Obesity (Silver Spring) 19, 792–799 (2011).

    Article  CAS  Google Scholar 

  70. Wellen, K. E. & Hotamisligil, G. S. Inflammation, stress, and diabetes. J. Clin. Invest. 115, 1111–1119 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Summers, S. A. Ceramides in insulin resistance and lipotoxicity. Prog. Lipid Res. 45, 42–72 (2006).

    Article  CAS  PubMed  Google Scholar 

  72. Erion, D. M. & Shulman, G. I. Diacylglycerol-mediated insulin resistance. Nat. Med. 16, 400–402 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Lee, J. Y., Sohn, K. H., Rhee, S. H. & Hwang, D. Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. J. Biol. Chem. 276, 16683–16689 (2001).

    Article  CAS  PubMed  Google Scholar 

  74. Lee, J. Y. et al. Saturated fatty acid activates but polyunsaturated fatty acid inhibits Toll-like receptor 2 dimerized with Toll-like receptor 6 or 1. J. Biol. Chem. 279, 16971–16979 (2004).

    Article  CAS  PubMed  Google Scholar 

  75. Wong, S. W. et al. Fatty acids modulate Toll-like receptor 4 activation through regulation of receptor dimerization and recruitment into lipid rafts in a reactive oxygen species-dependent manner. J. Biol. Chem. 284, 27384–27392 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Huang, S. et al. Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways. J. Lipid Res. 53, 2002–2013 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Sampey, B. P. et al. Metabolomic profiling reveals mitochondrial-derived lipid biomarkers that drive obesity-associated inflammation. PLoS ONE 7, e38812 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Mutomba, M. C. et al. Regulation of the activity of caspases by L-carnitine and palmitoylcarnitine. FEBS Lett. 478, 19–25 (2000).

    Article  CAS  PubMed  Google Scholar 

  79. Katoh, N., Wrenn, R. W., Wise, B. C., Shoji, M. & Kuo, J. F. Substrate proteins for calmodulin-sensitive and phospholipid-sensitive Ca2+-dependent protein kinases in heart, and inhibition of their phosphorylation by palmitoylcarnitine. Proc. Natl Acad. Sci. USA 78, 4813–4817 (1981).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Requero, M. A., Gonzalez, M., Goni, F. M., Alonso, A. & Fidelio, G. Differential penetration of fatty acyl-coenzyme A and fatty acylcarnitines into phospholipid monolayers. FEBS Lett. 357, 75–78 (1995).

    Article  CAS  PubMed  Google Scholar 

  81. Wise, B. C. et al. Phospholipid-sensitive Ca2+-dependent protein kinase from heart. II. Substrate specificity and inhibition by various agents. J. Biol. Chem. 257, 8489–8495 (1982).

    Article  CAS  PubMed  Google Scholar 

  82. Nakadate, T. & Blumberg, P. M. Modulation by palmitoylcarnitine of protein kinase C activation. Cancer Res. 47, 6537–6542 (1987).

    CAS  PubMed  Google Scholar 

  83. Oh, S. Y., Madhukar, B. V. & Trosko, J. E. Inhibition of gap junctional blockage by palmitoyl carnitine and TMB-8 in a rat liver epithelial cell line. Carcinogenesis 9, 135–139 (1988).

    Article  CAS  PubMed  Google Scholar 

  84. Moraru, II, Laky, M., Stanescu, T., Buzila, L. & Popescu, L. M. Protein kinase C controls Fcγ receptor-mediated endocytosis in human neutrophils. FEBS Lett. 274, 93–95 (1990).

    Article  CAS  PubMed  Google Scholar 

  85. Nakaki, T., Mita, S., Yamamoto, S., Nakadate, T. & Kato, R. Inhibition by palmitoylcarnitine of adhesion and morphological changes in HL-60 cells induced by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res. 44, 1908–1912 (1984).

    CAS  PubMed  Google Scholar 

  86. Nalecz, K. A., Mroczkowska, J. E., Berent, U. & Nalecz, M. J. Effect of palmitoylcarnitine on the cellular differentiation, proliferation and protein kinase C activity in neuroblastoma nb-2a cells. Acta Neurobiol. Exp. (Wars) 57, 263–274 (1997).

    CAS  Google Scholar 

  87. Muoio, D. M. et al. Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. Cell Metab. 15, 764–777 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Schenkel, L. C. & Bakovic, M. Formation and regulation of mitochondrial membranes. Int. J. Cell Biol. 2014, 709828 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Horvath, S. E. & Daum, G. Lipids of mitochondria. Prog. Lipid Res. 52, 590–614 (2013).

    Article  CAS  PubMed  Google Scholar 

  90. Mochly-Rosen, D., Das, K. & Grimes, K. V. Protein kinase C, an elusive therapeutic target? Nat. Rev. Drug Discov. 11, 937–957 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank J. Vockley (University of Pittsburgh, PA, USA) for critical review of the manuscript. The authors acknowledge research support from the US Department of Agriculture–Agricultural Research Service, the NIH (NIH-NIDDK R01-DK-078328 and R01-DK-078328-02S1) and the American Diabetes Association (1-12-BS-02). C.S.M. was supported by a T32 predoctoral training award, funded by the NIH National Center for Advancing Translational Sciences (UL1-TR-000002 and linked award TL1-TR-000133).

Author information

Authors and Affiliations

  1. Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, 66160, KS, USA

    Colin S. McCoin

  2. Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, 1089 Veterinary Medicine Drive, Davis, 95616, CA, USA

    Trina A. Knotts

  3. Arkansas Children's Nutrition Center and Department of Pediatrics, University of Arkansas for Medical Sciences, 15 Children's Way, Little Rock, 72202, AR, USA

    Sean H. Adams

Authors
  1. Colin S. McCoin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Trina A. Knotts
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sean H. Adams
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

C.S.M. and T.A.K. researched the data for the article. C.S.M. wrote the article. C.S.M., T.A.K. and S.H.A. contributed equally to the discussion of the content and to reviewing and/or editing of the article before submission.

Corresponding author

Correspondence to Sean H. Adams.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

McCoin, C., Knotts, T. & Adams, S. Acylcarnitines—old actors auditioning for new roles in metabolic physiology. Nat Rev Endocrinol 11, 617–625 (2015). https://doi.org/10.1038/nrendo.2015.129

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrendo.2015.129

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing