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Measurement of myocardial fatty acid esterification using [1-11C]palmitate and PET: comparison with direct measurements of myocardial triglyceride synthesis

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Journal of Nuclear Cardiology Aims and scope

Abstract

Background

The purpose of the present study was to assess the accuracy of rates of myocardial fatty acid esterification (MFAE) obtained using positron emission tomography (PET).

Methods and results

Sixteen dogs were studied after an overnight fast (FAST), during a euglycemic hyperinsulinemic clamp (CLAMP), or during infusion of intralipid (IL) or IL plus dobutamine (IL/DOB). MFAE was quantified using [1-11C]palmitate and PET and compared to the rate of triglyceride (TG) synthesis measured using [1-13C]palmitate and tissue sampling. Plasma free fatty acid (FFA) concentration varied ~20-fold across groups, with this variation in FFA availability accompanied by a ~20-fold range in TG synthesis. MFAE varied ~12-fold across groups, and was significantly correlated with TG synthesis (R = 0.80, P < .001). MFAE, however, was 3- to 4-fold higher than TG synthesis in FAST, CLAMP, and IL, but only ~50% higher when cardiac work was increased in IL/DOB, suggesting that MFAE reflects, in part, the incorporation of label into amino acids via TCA cycle exchange reactions.

Conclusions

Changes in MFAE parallel changes in TG synthesis, at least in the basal state. Although the data need to be interpreted cautiously, such measurements should be useful for quantifying acute changes in FFA storage by the heart in various pathophysiological states.

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References

  1. Borradaile NM, Schaffer JE. Lipotoxicity in the heart. Curr Hypertens Rep 2005;7:412-7.

    Article  CAS  PubMed  Google Scholar 

  2. Park T-S, Yamashita H, Blaner WS, Goldberg IJ. Lipids in the heart: A source of fuel and a source of toxins. Curr Opin Lipidol 2007;18:277-82.

    Article  CAS  PubMed  Google Scholar 

  3. Bergmann SR, Weinheimer CJ, Markham J, Herrero P. Quantitation of myocardial fatty acid metabolism using PET. J Nucl Med 1996;37:1730-2.

    Google Scholar 

  4. de las Fuentes L, Herrero P, Peterson LR, Kelly DP, Gropler RJ, Dávila-Román VG. Myocardial fatty acid metabolism: Independent predictor of left ventricular mass in hypertensive heart disease. Hypertens 2003;41:83-7.

    Article  CAS  Google Scholar 

  5. Kates AM, Herrero P, Dence C, Soto P, Srinivasan M, Delano DG, et al. Impact of aging on substrate metabolism by the human heart. J Am Coll Cardiol 2003;41:293-9.

    Article  CAS  PubMed  Google Scholar 

  6. Peterson LR, Herrero P, Schechtman KB, Racette SB, Waggoner AD, Kisrieva-Ware Z, et al. Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women. Circulation 2004;109:2191-6.

    Article  PubMed  Google Scholar 

  7. Herrero P, Soto PF, Dence CS, Kisrieva-Ware Z, Delano DA, Peterson LR, et al. Impact of hormone replacement therapy on myocardial fatty acid metabolism: Potential role of estrogen. J Nucl Cardiol 2005;12:574-81.

    Article  PubMed  Google Scholar 

  8. Herrero P, Peterson LR, McGill JB, Matthew S, Lesniak D, Dence C, et al. Increased myocardial fatty acid metabolism in patients with type I diabetes mellitus. J Am Coll Cardiol 2006;47:598-604.

    Article  CAS  PubMed  Google Scholar 

  9. Peterson LR, Herrero P, McGill J, Schechtman KB, Kisrieva-Ware Z, Lesniak D, et al. Fatty acids and insulin modulate myocardial substrate metabolism in humans with type I diabetes. Diabetes 2008;57:32-40.

    Article  CAS  PubMed  Google Scholar 

  10. Herrero P, Dence CS, Coggan AR, Kisrieva-Ware Z, Eisenbeis P, Gropler RJ. L-3-11C-Lactate as a PET tracer of myocardial lactate metabolism: A feasibility study. J Nucl Med 2007;48:2046-55.

    Article  CAS  PubMed  Google Scholar 

  11. Herrero P, Kisrieva-Ware Z, Dence CS, Patterson B, Coggan AR, Han DH, et al. PET measurements of myocardial glucose metabolism with 1-11C-glucose and kinetic modeling. J Nucl Med 2007;48:955-64.

    Article  CAS  PubMed  Google Scholar 

  12. Pearce GA, Brown KF. Heat inhibition of in vitro lipolysis and 14C ibuprofen protein binding in plasma from heparinized uraemic subjects. Life Sci 1983;33:1457-66.

    Article  CAS  PubMed  Google Scholar 

  13. Patterson BW, Zhao G, Elias N, Hachey DL, Klein S. Validation of a new procedure to determine plasma fatty acid concentration and isotopic enrichment. J Lipid Res 1999;40:2118-24.

    CAS  PubMed  Google Scholar 

  14. van der Vusse GJ, Roemen THM. Gradient of fatty acids from blood plasma to skeletal muscle in dogs. J Appl Physiol 1995;78:1839-43.

    PubMed  Google Scholar 

  15. Ruiz J, Antequera T, Andres AI, Petron MJ, Muriel E. Improvement of a solid phase extraction method for analysis of lipid fractions in muscle foods. Anal Chim Acta 2004;520:201-5.

    Article  CAS  Google Scholar 

  16. Guo ZK, Jensen MD. Determination of skeletal muscle triglyceride synthesis using a single muscle biopsy. Metabolism 2002;51:1198-205.

    Article  CAS  PubMed  Google Scholar 

  17. Bergmann SR, Herrero P, Matkham J, Weinheimer CJ, Walsh MN. Noninvasive quantitation of myocardial blood flow in human subjects with oxygen-15-labeled water and positron emission tomography. J Am Coll Cardiol 1989;14:639-52.

    Article  CAS  PubMed  Google Scholar 

  18. Herrero P, Markham J, Bergmann SR. Quantitation of myocardial blood flow with H2 15O and positron emission tomography: Assessment and error analysis of a mathematical approach. J Comput Assist Tomogr 1989;13:862-73.

    Article  CAS  PubMed  Google Scholar 

  19. Zilversmit DB. The design and analysis of isotope experiments. Ann J Med 1960;29:832-48.

    CAS  Google Scholar 

  20. van der Vusse GJ, Roemen THM, Prinzen FW, Coumans WA, Reneman RS. Uptake and tissue content of fatty acids in dog myocardium under normoxic and ischemic conditions. Circ Res 1982;50:538-46.

    PubMed  Google Scholar 

  21. O’Donnell JM, Zampino M, Alpert NM, Fasano MJ, Geenen DL, Lewandowski ED. Accelerated triacylglycerol turnover kinetics in hearts of diabetic rats include evidence for compartmented lipid storage. Am J Physiol 2006;290:E448-55.

    Google Scholar 

  22. Crass MF 3rd, Pieper GM. Lipid and glycogen metabolism in the hypoxic heart: Effects of epinephrine. Am J Physiol 1975;229:885-9.

    CAS  PubMed  Google Scholar 

  23. Olson RE. Effect of pyruvate and acetoacetate on the metabolism of fatty acids by the perfused rat heart. Nature (Lond) 1962;195:597-9.

    Article  CAS  Google Scholar 

  24. Saddick M, Lopaschuk GD. Myocardial triglyceride turnover and contributions to energy substrate utilization in isolated working rat hearts. J Biol Chem 1991;266:8162-70.

    Google Scholar 

  25. Nellis SH, Liedtke AJ, Renstrom B. Fatty acid kinetics in aerobic myocardium: Characteristics of tracer carbon entry and washout and the influence of metabolic demand. J Nucl Med 1992;33:1864-74.

    CAS  PubMed  Google Scholar 

  26. Rosamond TL, Abendschein DR, Sobel BE, Bergmann SR, Fox KAA. Metabolic fate of radiolabeled palmitate in ischemic canine myocardium: Implications for positron emission tomography. J Nucl Med 1987;28:1322-9.

    CAS  PubMed  Google Scholar 

  27. Daniel AM, Kapadia B, MacLean LD. Fatty acid supply and organ phospholipid turnover in two canine shock models. J Surg Res 1983;35:218-26.

    Article  CAS  PubMed  Google Scholar 

  28. Burgess SC, Babcock EE, Jeffrey FMH, Sherry AD, Malloy CR. NMR indirect detection of glutamate to measure citric acid cycle flux in isolated perfused mouse heart. FEBS Lett 2001;505:163-7.

    Article  CAS  PubMed  Google Scholar 

  29. Chance EM, Seeholzer SH, Kobayashi K, Williamson JR. Mathematical analysis of isotope labeling in the citric acid cycle with applications to 13C NMR studies in perfused rat hearts. J Biol Chem 1983;258:13785-94.

    CAS  PubMed  Google Scholar 

  30. O’Donnell JM, Kudej RK, LaNoue KF, Vatner SF, Lewandowski ED. Limited transfer of cytosolic NADH into mitochondria at high cardiac workload. Am J Physiol 2004;286:H2237-42.

    Google Scholar 

  31. Robitaille PM, Rath DP, Abduljalil AM, O’Donnell JM, Jiang Z, Zhang H, et al. Dynamic 13C NMR analysis of oxidative metabolism in the in vivo canine myocardium. J Biol Chem 1993;268:26296-301.

    CAS  PubMed  Google Scholar 

  32. Kisrieva-Ware Z, Coggan AR, Sharp TL, Dence CS, Gropler RJ, Herrero P. Assessment of myocardial triglyceride oxidation with PET and 11C-palmitate. J Nucl Cardiol (in press).

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Acknowledgments

This research was supported by NIH grants HL-69100, RR-000954, DK-020579, and DK-056341.

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Correspondence to Andrew R. Coggan PhD.

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Coggan, A.R., Kisrieva-Ware, Z., Dence, C.S. et al. Measurement of myocardial fatty acid esterification using [1-11C]palmitate and PET: comparison with direct measurements of myocardial triglyceride synthesis. J. Nucl. Cardiol. 16, 562–570 (2009). https://doi.org/10.1007/s12350-009-9102-0

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  • DOI: https://doi.org/10.1007/s12350-009-9102-0

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