Skip to main content
Log in

Lipid metabolism in the heart —Contribution of BMIPP to the diseased heart—

  • Review
  • Published:
Annals of Nuclear Medicine Aims and scope Submit manuscript

Abstract

Lipid contributes greatly in cardiac metabolism to produce high energy ATPs, and is suggested to be related to the progression and deterioration of heart disease. It is fortunate that the I-123-betamethyliodophenylpentadecanoic acid (BMIPP) imaging technique is now available in determining heart condition, but we must be cautious about the interpretation of images obtained with this new tracer. From the uptake of BMIPP into the cell to breakdown and catabolism of it, there exist so many critical enzymatical pathways relating to the modification of BMIPP imaging. In clinical evaluation, the image will be translated as the integral effects of these pathways. In other words, we must be aware of these critical pathways regulating lipid metabolism and modifying factors in order to correctly understand BMIPP imaging.

Lipid transport is affected by the albumin/FFA ratio in the blood, and extraction with membrane transporter proteins. Fatty acid binding protein (FABP) in the cytosole will play an important role in regulating lipid flux and following metabolism. Lipid will be utilized either for oxidation, triglyceride or phospholipid formation. For oxidation, carnitine palmitoil transferase is the key enzyme for the entrance of lipid into mitochondria, and oxidative enzymes such as acyl CoA dehydrogenase (MCAD, LCAD, HAD) will determine lipid use for the TCA cycle. ATPs produced in the mitochondria again limit the TG store.

It is well known that BMIPP imaging completely changes in the ischemic condition, and is also shown that lipid metabolical regulation completely differs from normal in the very early phase of cardiac hypertrophy. In the process of deteriorating heart failure, metabolical switching of lipid with glucose will take place.

In such a different heart disease conditions, it is clear that lipid metabolical regulation, including many lipid enzymes, works differently from in the healthy condition. These lipid enzymes are regulated by nuclear factor peroxisome proliferator-activated receptors (PPAR) just like a conductor of an orchestra. Most of the regulating mechanisms of the PPAR are still unknown, but reduction of this nuclear factor is shown in the process of decompensated heart failure.

This review is based by mostly on our fundamental and Japanese clinical data. BMIPP has been used clinically in abundant cases in Japan. In such situations, further correct information on lipid metabolism, including BMIPP, will contribute to the understanding of deteriorating heart disease and its prognosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Levine E, Elmaleh DR, Barlai-Kovach MM, et al. Radioiodinated beta-methyl phenyl fatty acid as potential tracers for myocardial imaging and metabolism.Eur Heart J 1985; 6: 85–90.

    Google Scholar 

  2. Dudzack R, Schmoliner R, Angelberger P, et al. Structurally modified fatty acids—clinical potential as tracers of metabolism.Eur Heart J 1986; 12: S45–48.

    Google Scholar 

  3. Knapp FF Jr, Kropp J. Iodine-123-labeled fatty acids for myocardial single photon emission tomography: Current status and future perspectives.Eur J Nucl Med 1995; 22: 3.

    Google Scholar 

  4. Knapp FF Jr, Kropp J, Franken PR, et al. Pharmacokinetics of radioiodinated fatty acid myocardial imaging agents in animal models and human studies.Quart J Nucl Med 1996; 40: 252–269.

    Google Scholar 

  5. Yamamichi Y, Kusuoka H, Morishita K, et al. Metabolism of iodine-123-BMIPP in perfused rat hearts.J Nucl Med 1995; 36: 1043–1050.

    PubMed  CAS  Google Scholar 

  6. Hosokawa R, Nohara R, Fujibayashi Y, et al. Metabolic fate of I-123 BMIPP in canine myocardium after administration of etomoxir.J Nucl Med 1996; 37: 1836–1840.

    PubMed  CAS  Google Scholar 

  7. Tamaki N, Tadamura E, Kawamoto M, et al. Decreased uptake of iodinated branched fatty acid analog indicates metabolic alterations in ischemic myocardium.J Nucl Med 1995; 36: 1974–1980.

    PubMed  CAS  Google Scholar 

  8. Tadamura E, Tamaki N, Matsumori A, et al. Myocardial metabolic changes in hypertrophic cardiomyopathy.J Nucl Med 1996; 37: 572–577.

    PubMed  CAS  Google Scholar 

  9. Hosokawa R, Nohara R, Fujibayashi Y, et al. Myocardial metabolism of BMIPP during low flow ischemia in an experimental model. Comparison with myocardial blood flow and FDG.Eur J Nucl Med 2001. (in press)

  10. Vyska K, Meyer W, Stremmel W, et al. Fatty acid uptake in normal human myocardium.Circ Res 1991; 69: 857–870.

    PubMed  CAS  Google Scholar 

  11. Nohara R, Hosokawa R, Hirai T, et al. Effect of metabolic substrate on BMIPP metabolism in canine myocardium.J Nucl Med 1998; 39: 1132–1137.

    PubMed  CAS  Google Scholar 

  12. Schaap FG, Van der Vusse GJ, Glatz JFC. Fatty acid-binding proteins in the heart.Mol Cell Biochem 1998; 180: 43–51.

    Article  PubMed  CAS  Google Scholar 

  13. Abumrad NA, El Maghrabi MR, Amri EZ, et al. Cloning of a rat adipocyte membrane protein implicated in binding or transport of long chain fatty acids that is induced during preadipocyte differentiation. Homology with human CD36.J Biol Chem 1993; 268: 17665–17668.

    PubMed  CAS  Google Scholar 

  14. Coburn TC, Knapp FF, Febbraio M, et al. Defective uptake and utilization of long chain fatty acids in muscle and adipose tissue of CD36 knockout mice.J Biol Chem 2000; 275: 32523–32529.

    Article  PubMed  CAS  Google Scholar 

  15. Lerch RA, Ambos HD, Bergman SD, et al. Localization of viable, ischemic myocardium by positron emission tomography with C11-palmitate.Circulation 1981; 64: 689–699.

    PubMed  CAS  Google Scholar 

  16. Weiss ES, Hoffman EJ, Phelps ME, et al. External detection and visualization of myocardial ischemia with C-11 substratein vivo andin vitro.Circ Res 1976; 39: 24–32.

    PubMed  CAS  Google Scholar 

  17. Fox KAA, Abendshein DR, Ambos HD, et al. Efflux of metabolized and nonmetabolized fatty acid from canin myocardium. Implications for quantifying myocardial metabolism tomographically.Circ Res 1985; 57: 232–243.

    PubMed  CAS  Google Scholar 

  18. Rosamond TL, Abendshein DR, Sobel BE, et al. The metabolic fate of radiolabeled palmitate in ischemic canine myocardium: Implications for positron tomography.J Nucl Med 1987; 28: 1322–1329.

    PubMed  CAS  Google Scholar 

  19. Fujibayashi Y, Nohara R, Hosokawa R, et al. Metabolism and kinetics of I-123 BMIPP in canine myocardium.J Nucl Med 1996; 37: 757–761.

    PubMed  CAS  Google Scholar 

  20. Hosokawa R, Nohara R, Fujibayashi Y, et al. Myocardial kinetics of I-123 BMIPP in canine myocardium after regional ischemia and reperfusion: Implications for clinical SPECT.J Nucl Med 1997; 38: 1857–1863.

    PubMed  CAS  Google Scholar 

  21. Heuckeroth RO, Birkenmeier EH, Levin MS, et al. Analysis of the tissue-specific expression, developmental regulation, and linkage relationships of a rodent genes encoding heart fatty acid binding protein.J Biol Chem 1987; 262: 9709–9717.

    PubMed  CAS  Google Scholar 

  22. Linssen MC, Vork MM, De Jong YF, et al. Fatty acid oxidation capacity and fatty acid binding protein content of different cell types isolated from rat heart.Mol Cell Biochem 1990; 98: 19–25.

    Article  PubMed  CAS  Google Scholar 

  23. Glatz JFC, Borchers T, Spencer F, et al. Fatty acid in cell signaling. Modulation by lipid binding proteins.Prostaglandins Leukot Essent Fatty Acids 1995; 52: 121–127.

    Article  PubMed  CAS  Google Scholar 

  24. Yoshimoto K, Tanaka T, Somiya K, et al. Human heart-type cytoplasmic fatty acid-binding protein as an indicator of acute myocardial infarction.Heart Vessels 1995; 10: 304–309.

    Article  PubMed  CAS  Google Scholar 

  25. Schaap FG, Binas B, Danneberg H, et al. Impaired longchain fatty acid utilization by cardiac myocytes isolated from mice lacking the heart-type fatty acid binding protein gene.Circ Res 1999; 85: 329–337.

    PubMed  CAS  Google Scholar 

  26. Hirai T, Nohara R, Hosokawa R, et al. Evaluation of myocardial infarct size in rat heart by pinhole SPECT.J Nucl Cardiol 2000; 7: 107–111.

    Article  PubMed  CAS  Google Scholar 

  27. Hirai T, Nohara R, Ogoh S, et al. Serial evaluation of fatty acid metabolism in rats with myocardial infarction by pinhole SPECT.J Nucl Cardiol 2001; 8. (in press)

  28. Fujibayashi Y, Yonekura Y, Takemura Y, et al. A myocardial accumulation of iodinated betamethyl-branched fatty acid analogue, I-125 BMIPP in relation to ATP concentration.J Nucl Med 1990; 31: 1818–1822.

    PubMed  CAS  Google Scholar 

  29. Nohara R, Okuda K, Ogino M, et al. Evaluation of myocardial viability with I-123 BMIPP in a canine model.J Nucl Med 1996; 37: 1403–1407.

    PubMed  CAS  Google Scholar 

  30. Schoonderwoerd K, Broekhoven SS, Hulsmann WC, et al. Involvement of lysozome-like particles in the metabolism of endogeneous myocardial triglycerides during ischemia/reperfusion. Uptake and degradation of triglycerides by lysozomes isolated from rat heart.Basic Res Cardiol 1990; 85: 153–163.

    Article  PubMed  CAS  Google Scholar 

  31. Schoonderwoerd K, Broekhoven SS, Hulsmann WC, et al. Enhanced lipolysis of myocardial triglycerides during low-flow ischemia and anoxia in the isolated rat heart.Basic Res Cardiol 1989; 84: 165–173.

    Article  PubMed  CAS  Google Scholar 

  32. Langer GA. The effect of PH on cellular and membrane calcium binding and contraction of myocardium. A possible role for sarcolemmal Pl in EC coupling.Circ Res 1985; 57: 374–382.

    PubMed  CAS  Google Scholar 

  33. Corr PB, Gross RW, Sobel BE. Arrythmogenic amphophilic lipids and the myocardial cell membrane. [editorial]J Mol Cell Cardiol 1996; 78: 482–491.

    Google Scholar 

  34. Davies NJ, Lonlin RE, Lopaschuk GD. Effect of exogenous fatty acids on reperfusion arrythmias in isolated working perfused hearts.Am J Physiol 1992; 262: H1796-H1801.

    PubMed  CAS  Google Scholar 

  35. Emberger T, Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: A nuclear receptor signaling pathway in lipid physiology.Ann Rev Cell Dev Biol 1996; 12: 335–363.

    Article  Google Scholar 

  36. Schoonjans K, Staers B, Auwerx J. The peroxisome proliferator activated receptors (PPARs) and their effects on lipid metabolism and adipocyte differentiation.Biochimica Biophy Acta 1996; 1302: 93–109.

    CAS  Google Scholar 

  37. Kanda H, Nohara R, Hasegawa K, et al. Peroxisome proliferator activated receptor dependent pathways suppress myocardial cell hypertrophy.Circulation 1999; suppl 100: I-664.

    Google Scholar 

  38. Kanda H, Nohara R, Hasegawa K, et al. A nuclear complex containing PPARa/RXRa is markedly down regulated in the hypertrophied rat left ventricular myocardium with normal systolic function.Heart Vessels 2000; 15: 191–196.

    Article  PubMed  CAS  Google Scholar 

  39. Sack MN, Rader TA, Park S, et al. Fatty acid oxidation enzyme gene expression is down regulated in the failing heart.Circulation 1996; 94: 2837–2842.

    PubMed  CAS  Google Scholar 

  40. Kataoka K, Nohara R, Hirai T, et al. Impaired fatty acid metabolism precedes left ventricular hypertrophy in pressure overloaded rats.J Nucl Cardiol 2001; 8 (suppl): S88. (abstract)

    Article  Google Scholar 

  41. Wolkowicz PE, Urthaler F, Forrest C, et al. 2-Tetradecylglycidic acid, an inhibitor of carnitine palmitoyltransferase-1, induces myocardial hypertrophy via the AT1 receptor.J Mol Cell Cardiol 1999; 31: 1405–1412.

    Article  PubMed  CAS  Google Scholar 

  42. Remondino A, Rosenblatt-Velin N, Nontessuit C, et al. Altered expression of proteins of metabolic regulation during remodeling of the left ventricle after myocardial infarction.J Mol Cell Cardiol 2000; 32: 2025–2034.

    Article  PubMed  CAS  Google Scholar 

  43. Yonekura Y, Brill AB, Som P, et al. Regional myocardial substrate uptake in hypertensive rats: a quantitative autoradiographic measurement.Science 1985; 227: 1494–1496.

    Article  PubMed  CAS  Google Scholar 

  44. Nakamura T, Sugihara H, Kinoshita N, et al. Can serum carnitine levels distinguish hypertrophic cardiomyopathy from hypertensive hearts?Hypertension 2000; 36: 215–219.

    PubMed  CAS  Google Scholar 

  45. Tadamura E, Kudoh T, Hattori N, et al. Impairement of BMIPP uptake precedes abnormalities in oxygen and glucose metabolism in hypertrophic cardiomyopathy.J Nucl Med 1998; 39: 390–396.

    PubMed  CAS  Google Scholar 

  46. Takeishi Y, Chiba J, Abe S, et al. Heterogenous myocardial distribution of BMIPP in patients with hypertrophic cardiomyopathy.Eur J Nucl Med 1992; 19: 775–782.

    Article  PubMed  CAS  Google Scholar 

  47. Taki J, Nakajima K, Bunko H, et al. I-123-labeled BMIPP fatty acid myocardial scintigraphy in patients with hypertrophic cardiomyopathy.Nucl Med Commun 1994; 14: 181–188.

    Article  Google Scholar 

  48. Ohtsuki K, Sugihara H, Kuribayashi T, et al. Impairment of BMIPP accumulation at junction of ventricular septum and left and right ventricular free wall in hypertrophic cardiomyopathy.J Nucl Med 1999; 40: 2007–2013.

    PubMed  CAS  Google Scholar 

  49. Hashimoto Y, Yamabe H, Yokoyama M, et al. Myocardial defect detected by BMIPP scintigraphy and left ventricular dysfunction in patients with idiopathic dilated cardiomyopathy.Ann Nucl Med 1996; 10: 225–230.

    PubMed  CAS  Google Scholar 

  50. Ishida Y, Yasumura Y, Nagaya N, et al. Myocardial imaging with BMIPP in patients with congestive heart failure.Int J Cardiac Imaging 1999; 15: 71–77.

    Article  CAS  Google Scholar 

  51. Kataoka K, Nohara R, Hosokawa R, et al. Myocardial lipid metabolism in compensated and advanced stages of heart failure—Evaluation by canine pacing model with BMIPP—.J Nucl Med 2001; 42: 124–129.

    PubMed  CAS  Google Scholar 

  52. Recchia FA, McConnel PI, Bernstein RD, et al. Reduced nitric oxide production and altered myocardial metabolism during the decompensation of pacing induced heart failure in the conscious dog.Circ Res 1998; 83: 969–979.

    PubMed  CAS  Google Scholar 

  53. Tamaki N, Tadamura E, Kawamoto M, et al. Decreased uptake of iodinated branched fatty acid analogue indicates metabolic alterations in ischemic myocardium.J Nucl Med 1995; 36: 1974–1980.

    PubMed  CAS  Google Scholar 

  54. Franken PR, Dendale P, DeGeeter F, et al. Prediction of functional outcome after myocardial infarction using BMIPP and SESTAMIBI scintigraphy.J Nucl Med 1996; 37: 718–722.

    PubMed  CAS  Google Scholar 

  55. Hambye ASE, Dobbeleir AA, Franken PR, et al. BMIPP imaging to improve the value of sestamibi scintigraphy for predicting functional outcome in severe chronic ischemic left ventricular dysfunction.J Nucl Med 1999; 40: 1468–1476.

    PubMed  CAS  Google Scholar 

  56. Hirai T, Nohara R, Ogoh S, et al. Serial evaluation of fatty acid metabolism in rats with myocardial infarction by pinhole SPECT.J Nucl Cardiol 2001; 8. (in press).

  57. Nishimura T, Nagata S, Uehara T, et al. Prognosis of hypertrophic cardiomyopathy: assessment by BMIPP myocardial single photon emission computed tomography.Ann Nucl Med 1996; 10: 71–78.

    PubMed  CAS  Google Scholar 

  58. Yazaki Y, Isobe M, Takahashi W, et al. Assessment of myocardial fatty acid metabolic abnormalities in patients with idiopathic dilated cardiomyopathy using BMIPP SPECT.Heart 1999; 81: 153–159.

    PubMed  CAS  Google Scholar 

  59. Nakata T, Kobayashi T, Tamaki N, et al. Prognostic value of impaired myocardial fatty acid uptake in patients with acute myocardial infarction.Nucl Med Commun 2000; 21: 897–906.

    Article  PubMed  CAS  Google Scholar 

  60. Yoshinaga K, Tahara M, Torii H, et al. Predicting the effects on patients with dilated cardiomyopathy of betablocker therapy by using BMIPP myocardial scintigraphy.Ann Nucl Med 1998; 12: 341–347.

    Article  PubMed  CAS  Google Scholar 

  61. McNulty PH, Jagasia D, Cline GW, et al. Persistent changes in myocardial glucose metabolismin vivo during reperfusion of a limited-duration coronary occlusion.Circulation 2000; 101: 917–922.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ryuji Nohara.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nohara, R. Lipid metabolism in the heart —Contribution of BMIPP to the diseased heart—. Ann Nucl Med 15, 403–409 (2001). https://doi.org/10.1007/BF02988343

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02988343

Key words

Navigation