Assessment of myocardial metabolic flexibility and work efficiency in human type 2 diabetes using 16-[18F]fluoro-4-thiapalmitate, a novel PET fatty acid tracer

American Journal of Physiology - Endocrinology and Metabolism

Volumn 310, Issue 6, 2016, Pages E452-E460

  Mather, K J ^a   Hutchins, G D ^a   Perry, K ^a   Territo, W ^a   Chisholm, R ^a   Acton, A ^a   Glick Wilson, B ^a   Considine, R V ^a   Moberly, S ^a   DeGrado, T R ^a,b  

^a INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b MAYO CLINIC   (United States)

Author keywords

Diabetes; Heart; Metabolic flexibility; Metabolism; Myocardial; Positron emission tomography

Indexed keywords

ACETIC ACID C 11; FATTY ACID; FLUORO 4 THIAPALMITATE F 18; FUEL; GLUCOSE; HEMOGLOBIN A1C; INSULIN; TRACER; UNCLASSIFIED DRUG; 16-FLUORO-4-THIAPALMITIC ACID; FLUORINE; PALMITIC ACID DERIVATIVE; THIOKETONE;

ADULT; ARTICLE; CEREBROVASCULAR ACCIDENT; CLINICAL ARTICLE; CLINICAL ASSESSMENT; CONCENTRATION PROCESS; CONTROLLED STUDY; DIASTOLIC BLOOD PRESSURE; DIET RESTRICTION; FATTY ACID OXIDATION; FATTY ACID TRANSPORT; FEMALE; GLYCEMIC CONTROL; HEART MUSCLE METABOLISM; HEART MUSCLE OXYGEN CONSUMPTION; HEART MUSCLE PERFUSION; HEART RATE; HEART WORK; HUMAN; HYPERINSULINEMIC-EUGLYCEMIC CLAMP TECHNIQUE; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; SYSTOLIC BLOOD PRESSURE; CARDIAC MUSCLE; CASE CONTROL STUDY; DIAGNOSTIC IMAGING; DRUG EFFECTS; GLUCOSE CLAMP TECHNIQUE; HEART; LIPID METABOLISM; METABOLISM; MIDDLE AGED; OXIDATION REDUCTION REACTION; OXYGEN CONSUMPTION; PHYSIOLOGY; PRODUCTIVITY;

ADULT; CASE-CONTROL STUDIES; DIABETES MELLITUS, TYPE 2; EFFICIENCY; FATTY ACIDS; FEMALE; FLUORINE RADIOISOTOPES; GLUCOSE; GLUCOSE CLAMP TECHNIQUE; HEART; HUMANS; INSULIN; LIPID METABOLISM; MALE; MIDDLE AGED; MYOCARDIUM; OXIDATION-REDUCTION; OXYGEN CONSUMPTION; PALMITATES; POSITRON-EMISSION TOMOGRAPHY; THIONES;

EID: 84983751474     PISSN: 01931849     EISSN: 15221555     Source Type: Journal    
DOI: 10.1152/ajpendo.00437.2015     Document Type: Article

References (75)

1. Angin Y, Steinbusch LK, Simons PJ, Greulich S, Hoebers NT, Douma K, van Zandvoort MA, Coumans WA, Wijnen W, Diamant M, Ouwens DM, Glatz JF, Luiken JJ. CD36 inhibition prevents lipid accumulation and contractile dysfunction in rat cardiomyocytes. Biochem J 448: 43–53, 2012.
2. Baranowski M, Blachnio-Zabielska A, Zabielski P, Gorski J. Pioglitazone induces lipid accumulation in the rat heart despite concomitant reduction in plasma free fatty acid availability. Arch Biochem Biophys 477: 86–91, 2008.
3. Baron AD, Clark MG. Role of blood flow in the regulation of muscle glucose uptake. Annu Rev Nutr 17: 487–499, 1997.
4. Barrett EJ, Eggleston EM, Inyard AC, Wang H, Li G, Chai W, Liu Z. The vascular actions of insulin control its delivery to muscle and regulate the rate-limiting step in skeletal muscle insulin action. Diabetologia 52: 752–764, 2009.
5. Barrett EJ, Schwartz RG, Young LH, Jacob R, Zaret BL. Effect of chronic diabetes on myocardial fuel metabolism and insulin sensitivity. Diabetes 37: 943–948, 1988.
6. Barsotti A, Giannoni A, Di Napoli P, Emdin M. Energy metabolism in the normal and in the diabetic heart. Curr Pharm Des 15: 836–840, 2009.
7. Beanlands RS, Armstrong WF, Hicks RJ, Nicklas J, Moore C, Hutchins GD, Wolpers HG, Schwaiger M. The effects of afterload reduction on myocardial carbon 11-labeled acetate kinetics and noninvasively estimated mechanical efficiency in patients with dilated cardiomyopathy. J Nucl Cardiol 1: 3–16, 1994.
8. Bergman BC, Tsvetkova T, Lowes B, Wolfel EE. Myocardial FFA metabolism during rest and atrial pacing in humans. Am J Physiol Endocrinol Metab 296: E358–E366, 2009.
9. Bonen A, Campbell SE, Benton CR, Chabowski A, Coort SL, Han XX, Koonen DP, Glatz JF, Luiken JJ. Regulation of fatty acid transport by fatty acid translocase/CD36. Proc Nutr Soc 63: 245–249, 2004.
10. Borradaile NM, Schaffer JE. Lipotoxicity in the heart. Curr Hypertens Rep 7: 412–417, 2005.
11. Buck A, Wolpers HG, Hutchins GD, Savas V, Mangner TJ, Nguyen N, Schwaiger M. Effect of carbon-11-acetate recirculation on estimates of myocardial oxygen consumption by PET. J Nucl Med 32: 1950–1957, 1991.
12. Carley AN, Atkinson LL, Bonen A, Harper ME, Kunnathu S, Lopaschuk GD, Severson DL. Mechanisms responsible for enhanced fatty acid utilization by perfused hearts from type 2 diabetic db/db mice. Arch Physiol Biochem 113: 65–75, 2007.
13. Carley AN, Severson DL. Fatty acid metabolism is enhanced in type 2 diabetic hearts. Biochim Biophys Acta 1734: 112–126, 2005.
14. Carley AN, Severson DL. What are the biochemical mechanisms responsible for enhanced fatty acid utilization by perfused hearts from type 2 diabetic db/db mice? Cardiovasc Drugs Ther 22: 83–89, 2008.
15. Chabowski A, Gorski J, Glatz JF, Luiken JJ, Bonen A. Proteinmediated fatty acid uptake in the heart. Curr Cardiol Rev 4: 12–21, 2008.
16. Coort SL, Bonen A, van der Vusse GJ, Glatz JF, Luiken JJ. Cardiac substrate uptake and metabolism in obesity and type-2 diabetes: role of sarcolemmal substrate transporters. Mol Cell Biochem 299: 5–18, 2007.
17. Critchley LA. Impedance cardiography. The impact of new technology. Anaesthesia 53: 677–684, 1998.
18. DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol Endocrinol Metab Gastrointest Physiol 237: E214–E223, 1979.
19. DeGrado TR, Kitapci MT, Wang S, Ying J, Lopaschuk GD. Validation of 18F-fluoro-4-thia-palmitate as a PET probe for myocardial fatty acid oxidation: effects of hypoxia and composition of exogenous fatty acids. J Nucl Med 47: 173–181, 2006.
20. DeGrado TR, Moka DC. Non-beta-oxidizable omega-[18F]fluoro long chain fatty acid analogs show cytochrome P-450-mediated defluorination: implications for the design of PET tracers of myocardial fatty acid utilization. Int J Rad Appl Instrum B 19: 389–397, 1992.
21. DeGrado TR, Wang S, Holden JE, Nickles RJ, Taylor M, Stone CK. Synthesis and preliminary evaluation of (18)F-labeled 4-thia palmitate as a PET tracer of myocardial fatty acid oxidation. Nucl Med Biol 27: 221–231, 2000.
22. Dirkx E, Schwenk RW, Glatz JF, Luiken JJ, van Eys GJ. High fat diet induced diabetic cardiomyopathy. Prostaglandins Leukot Essent Fatty Acids 85: 219–225, 2011.
23. Giedd KN, Bergmann SR. Fatty acid imaging of the heart. Curr Cardiol Rep 13: 121–131, 2011.
24. Gimeno RE, Ortegon AM, Patel S, Punreddy S, Ge P, Sun Y, Lodish HF, Stahl A. Characterization of a heart-specific fatty acid transport protein. J Biol Chem 278: 16039–16044, 2003.
25. Glatz JF, Angin Y, Steinbusch LK, Schwenk RW, Luiken JJ. CD36 as a target to prevent cardiac lipotoxicity and insulin resistance. Prostaglandins Leukot Essent Fatty Acids 88: 71–77, 2013.
26. Govindarajan G, Hayden MR, Cooper SA, Figueroa SD, Ma L, Hoffman TJ, Stump CS, Sowers JR. Metabolic derangements in the insulin-resistant heart. J Cardiometab Syndr 1: 102–106, 2006.
27. Greenberg BH, Hermann DD, Pranulis MF, Lazio L, Cloutier D. Reproducibility of impedance cardiography hemodynamic measures in clinically stable heart failure patients. Congest Heart Fail 6: 74–80, 2000.
28. Guleria RS, Singh AB, Nizamutdinova IT, Souslova T, Mohammad AA, Kendall JA Jr, Baker KM, Pan J. Activation of retinoid receptormediated signaling ameliorates diabetes-induced cardiac dysfunction in Zucker diabetic rats. J Mol Cell Cardiol 57: 106–118, 2013.
29. Hallsten K, Virtanen KA, Lonnqvist F, Janatuinen T, Turiceanu M, Ronnemaa T, Viikari J, Lehtimaki T, Knuuti J, Nuutila P. Enhancement of insulin-stimulated myocardial glucose uptake in patients with Type 2 diabetes treated with rosiglitazone. Diabet Med 21: 1280–1287, 2004.
30. Hames KC, Vella A, Kemp BJ, Jensen MD. Free fatty acid uptake in humans with CD36 deficiency. Diabetes 63: 3606–3614, 2014.
31. Hutchins GD, Chen T, Carlson KA, Fain RL, Winkle W, Vavrek T, Mock BH, Zipes DP. PET imaging of oxidative metabolism abnormalities in sympathetically denervated canine myocardium. J Nucl Med 40: 846–853, 1999.
32. Kelley DE, Goodpaster B, Wing RR, Simoneau JA. Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss. Am J Physiol Endocrinol Metab 277: E1130–E1141, 1999.
33. Kelley DE, Mandarino LJ. Fuel selection in human skeletal muscle in insulin resistance: a reexamination. Diabetes 49: 677–683, 2000.
34. Keung W, Ussher JR, Jaswal JS, Raubenheimer M, Lam VH, Wagg CS, Lopaschuk GD. Inhibition of carnitine palmitoyltransferase-1 activity alleviates insulin resistance in diet-induced obese mice. Diabetes 62: 711–720, 2013.
35. Kim MS, Wang Y, Rodrigues B. Lipoprotein lipase mediated fatty acid delivery and its impact in diabetic cardiomyopathy. Biochim Biophys Acta 1821: 800–808, 2012.
36. Knuuti J, Takala TO, Nagren K, Sipila H, Turpeinen AK, Uusitupa MI, Nuutila P. Myocardial fatty acid oxidation in patients with impaired glucose tolerance. Diabetologia 44: 184–187, 2001.
37. Koonen DP, Glatz JF, Bonen A, Luiken JJ. Long-chain fatty acid uptake and FAT/CD36 translocation in heart and skeletal muscle. Biochim Biophys Acta 1736: 163–180, 2005.
38. Kota SK, Kota SK, Jammula S, Panda S, Modi KD. Effect of diabetes on alteration of metabolism in cardiac myocytes: therapeutic implications. Diabetes Technol Ther 13: 1155–1160, 2011.
39. Kovacs P, Stumvoll M. Fatty acids and insulin resistance in muscle and liver. Best Pract Res Clin Endocrinol Metab 19: 625–635, 2005.
40. Labbe SM, Grenier-Larouche T, Noll C, Phoenix S, Guerin B, Turcotte EE, Carpentier AC. Increased myocardial uptake of dietary fatty acids linked to cardiac dysfunction in glucose-intolerant humans. Diabetes 61: 2701–2710, 2012.
41. Labbe SM, Noll C, Grenier-Larouche T, Kunach M, Bouffard L, Phoenix S, Guerin B, Baillargeon JP, Langlois MF, Turcotte EE, Carpentier AC. Improved cardiac function and dietary fatty acid metabolism after modest weight loss in subjects with impaired glucose tolerance. Am J Physiol Endocrinol Metab 306: E1388–E1396, 2014.
42. Larsen TS, Aasum E. Metabolic (in)flexibility of the diabetic heart. Cardiovasc Drugs Ther 22: 91–95, 2008.
43. Lewandowski E, Ingwall J. The physiological chemistry of energy production in the heart. In: Hurst’s The Heart, edited by Schlant R, O’, Rourke R, Roberts R, Sonnenblick E. New York: McGraw-Hill, 1994, p. 153–164.
44. Luiken JJ. Sarcolemmal fatty acid uptake vs. mitochondrial beta-oxidation as target to regress cardiac insulin resistance. Appl Physiol Nutr Metab 34: 473–480, 2009.
45. Luiken JJ, Arumugam Y, Dyck DJ, Bell RC, Pelsers MM, Turcotte LP, Tandon NN, Glatz JF, Bonen A. Increased rates of fatty acid uptake and plasmalemmal fatty acid transporters in obese Zucker rats. J Biol Chem 276: 40567–40573, 2001.
46. Luiken JJ, Bonen A, Glatz JF. Cellular fatty acid uptake is acutely regulated by membrane-associated fatty acid-binding proteins. Prostaglandins Leukot Essent Fatty Acids 67: 73–78, 2002.
47. Mather KJ, Lteif AA, Veeneman E, Fain R, Giger S, Perry K, Hutchins GD. Role of endogenous ET-1 in the regulation of myocardial blood flow in lean and obese humans. Obesity (Silver Spring) 18: 63–70, 2010.
48. Mazumder PK, O’Neill BT, Roberts MW, Buchanan J, Yun UJ, Cooksey RC, Boudina S, Abel ED. Impaired cardiac efficiency and increased fatty acid oxidation in insulin-resistant ob/ob mouse hearts. Diabetes 53: 2366–2374, 2004.
49. McGill JB, Peterson LR, Herrero P, Saeed IM, Recklein C, Coggan AR, Demoss AJ, Schechtman KB, Dence CS, Gropler RJ. Potentiation of abnormalities in myocardial metabolism with the development of diabetes in women with obesity and insulin resistance. J Nucl Cardiol 18: 421–429; quiz 432–423, 2011.
50. Menard SL, Croteau E, Sarrhini O, Gelinas R, Brassard P, Ouellet R, Bentourkia M, van Lier JE, Des Rosiers C, Lecomte R, Carpentier AC. Abnormal in vivo myocardial energy substrate uptake in diet-induced type 2 diabetic cardiomyopathy in rats. Am J Physiol Endocrinol Metab 298: E1049–E1057, 2010.
51. Nemanich S, Rani S, Shoghi K. In vivo multi-tissue efficacy of peroxisome proliferator-activated receptor-gamma therapy on glucose and fatty acid metabolism in obese type 2 diabetic rats. Obesity (Silver Spring) 21: 2522–2529, 2013.
52. Ng CK, Huang SC, Schelbert HR, Buxton DB. Validation of a model for [1–11C]acetate as a tracer of cardiac oxidative metabolism. Am J Physiol Heart Circ Physiol 266: H1304–H1315, 1994.
53. Ng Y, Moberly SP, Mather KJ, Brown-Proctor C, Hutchins GD, Green MA. Equivalence of arterial and venous blood for [11C]CO2- metabolite analysis following intravenous administration of 1-[11C]acetate and 1-[11C]palmitate. Nucl Med Biol 40: 361–365, 2013.
54. Oakes ND, Thalen P, Aasum E, Edgley A, Larsen T, Furler SM, Ljung B, Severson D. Cardiac metabolism in mice: tracer method developments and in vivo application revealing profound metabolic inflexibility in diabetes. Am J Physiol Endocrinol Metab 290: E870–E881, 2006.
55. Patlak CS, Blasberg RG, Fenstermacher JD. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 3: 1–7, 1983.
56. Peterson LR, Herrero P, Schechtman KB, Racette SB, Waggoner AD, Kisrieva-Ware Z, Dence C, Klein S, Marsala J, Meyer T, Gropler RJ. Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women. Circulation 109: 2191–2196, 2004.
57. Peterson LR, Saeed IM, McGill JB, Herrero P, Schechtman KB, Gunawardena R, Recklein CL, Coggan AR, DeMoss AJ, Dence CS, Gropler RJ. Sex and type 2 diabetes: obesity-independent effects on left ventricular substrate metabolism and relaxation in humans. Obesity (Silver Spring) 20: 802–810, 2012.
58. Peterson LR, Soto PF, Herrero P, Mohammed BS, Avidan MS, Schechtman KB, Dence C, Gropler RJ. Impact of gender on the myocardial metabolic response to obesity. JACC Cardiovasc Imaging 1: 424–433, 2008.
59. Pulinilkunnil T, Kienesberger PC, Nagendran J, Sharma N, Young ME, Dyck JR. Cardiac-specific adipose triglyceride lipase overexpression protects from cardiac steatosis and dilated cardiomyopathy following diet-induced obesity. Int J Obes (Lond) 38: 205–215, 2014.
60. Ramanathan T, Morita S, Huang Y, Shirota K, Nishimura T, Zheng X, Hunyor SN. Glucose-insulin-potassium solution improves left ventricular energetics in chronic ovine diabetes. Ann Thorac Surg 77: 1408–1414, 2004.
61. Ramanathan T, Shirota K, Morita S, Nishimura T, Huang Y, Zheng X, Hunyor S. Left ventricular oxygen utilization efficiency is impaired in chronic streptozotocin-diabetic sheep. Cardiovasc Res 55: 749–756, 2002.
62. Rider OJ, Cox P, Tyler D, Clarke K, Neubauer S. Myocardial substrate metabolism in obesity. Int J Obes (Lond) 37: 972–979, 2013.
63. Rigo P, de Landsheere C, Melon P, Kulbertus H. Imaging of myocardial metabolism by positron emission tomography. Cardiovasc Drugs Ther Pharmacotherapy 4, Suppl 4: 847–851, 1990.
64. Samovski D, Sun J, Pietka T, Gross RW, Eckel RH, Su X, Stahl PD, Abumrad NA. Regulation of AMPK activation by CD36 links fatty acid uptake to beta-oxidation. Diabetes 64: 353–359, 2015.
65. Sorensen J, Valind S, Andersson LG. Simultaneous quantification of myocardial perfusion, oxidative metabolism, cardiac efficiency and pump function at rest and during supine bicycle exercise using 1-11Cacetate PET–a pilot study. Clin Physiol Funct Imaging 30: 279–284, 2010.
66. Storlien L, Oakes ND, Kelley DE. Metabolic flexibility. Proc Nutr Soc 63: 363–368, 2004.
67. Sun KT, Yeatman LA, Buxton DB, Chen K, Johnson JA, Huang SC, Kofoed KF, Weismueller S, Czernin J, Phelps ME, Schelbert HR. Simultaneous measurement of myocardial oxygen consumption and blood flow using [1-carbon-11]acetate. J Nucl Med 39: 272–280, 1998.
68. Timmer SA, Lubberink M, Germans T, Gotte MJ, ten Berg JM, ten Cate FJ, van Rossum AC, Lammertsma AA, Knaapen P. Potential of [11C]acetate for measuring myocardial blood flow: Studies in normal subjects and patients with hypertrophic cardiomyopathy. J Nucl Cardiol 17: 264–275, 2010.
69. Tuunanen H, Engblom E, Naum A, Nagren K, Hesse B, Airaksinen KE, Nuutila P, Iozzo P, Ukkonen H, Opie LH, Knuuti J. Free fatty acid depletion acutely decreases cardiac work and efficiency in cardiomyopathic heart failure. Circulation 114: 2130–2137, 2006.
70. Tuunanen H, Engblom E, Naum A, Nagren K, Scheinin M, Hesse B, Juhani Airaksinen KE, Nuutila P, Iozzo P, Ukkonen H, Opie LH, Knuuti J. Trimetazidine, a metabolic modulator, has cardiac and extracardiac benefits in idiopathic dilated cardiomyopathy. Circulation 118: 1250–1258, 2008.
71. Ukkonen H, Tops L, Saraste A, Naum A, Koistinen J, Bax J, Knuuti J. The effect of right ventricular pacing on myocardial oxidative metabolism and efficiency: relation with left ventricular dyssynchrony. Eur J Nucl Med Mol Imaging 36: 2042–2048, 2009.
72. van der Meer RW, Rijzewijk LJ, de Jong HW, Lamb HJ, Lubberink M, Romijn JA, Bax JJ, de Roos A, Kamp O, Paulus WJ, Heine RJ, Lammertsma AA, Smit JW, Diamant M. Pioglitazone improves cardiac function and alters myocardial substrate metabolism without affecting cardiac triglyceride accumulation and high-energy phosphate metabolism in patients with well-controlled type 2 diabetes mellitus. Circulation 119: 2069–2077, 2009.
73. Yang J, Sambandam N, Han X, Gross RW, Courtois M, Kovacs A, Febbraio M, Finck BN, Kelly DP. CD36 deficiency rescues lipotoxic cardiomyopathy. Circ Res 100: 1208–1217, 2007.
74. Yokoyama I, Yonekura K, Ohtake T, Kawamura H, Matsumoto A, Inoue Y, Aoyagi T, Sugiura S, Omata M, Ohtomo K, Nagai R. Role of insulin resistance in heart and skeletal muscle F-18 fluorodeoxyglucose uptake in patients with non-insulin-dependent diabetes mellitus. J Nucl Cardiol 7: 242–248, 2000.
75. 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 1801: 1–22, 2010.