Triglyceride Deposit Cardiomyovasculopathy

  • Ken-ichi HiranoEmail author
  • Ming Li
  • Yoshihiko Ikeda


Triglyceride deposit cardiomyovasculopathy (TGCV) is a novel disease concept we found in Japanese cardiac transplant candidates in 2008. Probands carried mutations in the PNPLA2 gene encoding adipose triglyceride lipase (ATGL). ATGL is the major enzyme that catalyzes the initial rate-limiting step of intracellular triglyceride hydrolysis to release free nonesterified long-chain fatty acids (LCFAs), which is an essential energy source for the normal heart. Patients with TGCV show ectopic accumulation of triglycerides in cardiomyocytes and smooth muscle cells resulting from abnormal intracellular metabolism of triglycerides and LCFA. TGCV is classified into primary and idiopathic TGCV with and without genetic ATGL deficiency, respectively. Both types of TGCV patients suffer from severe heart failure, arrhythmia, and coronary artery disease caused by lipotoxicity and energy failure at cellular levels. The Japan TGCV study group provided the diagnostic guideline and has been trying to develop a nutritional therapeutics with medium-chain fatty acids in order to overcome this intractable disease one day earlier. In this chapter, we describe clinical signs and symptoms, laboratory findings, diagnosis, and possible therapies of TGCV.


Adipose triglyceride lipase Heart failure Long-chain fatty acids Triglyceride deposit cardiomyovasculopathy Triglyceride 



Adipose triglyceride lipase


Body mass index


β-Methyl-p-[123I]-iodophenyl-pentadecanoic acid


Coronary artery bypass grafting


Cardiac transplantation


Heart failure


Long-chain fatty acids


Left ventricle


Neutral lipid storage disease with ichthyosis


Neutral lipid storage disease with myopathy


Percutaneous coronary intervention


Smooth muscle cells


Single-photon emission computed tomography




Triglyceride deposit cardiomyovasculopathy


Washout rate



This was partially supported by research grants for rare and intractable diseases from the Japan Agency of Medical Research and Development (AMED) (Grant No. 17ek0109092h0003) and from the Ministry of Health, Labour, and Welfare of Japan.


  1. Chen J, Hong D, Wang Z et al (2010) A novel PNPLA2 mutation causes neutral lipid storage disease with myopathy (NLSDM) presenting muscular dystrophic features with lipid storage and rimmed vacuoles. Clin Neuropathol 29:351–356CrossRefGoogle Scholar
  2. Coassin S, Schweiger M, Kloss-Brandstatter A et al (2010) Investigation and functional characterization of rare genetic variants in the adipose triglyceride lipase in a large healthy working population. PLoS Genet 6:e1001239CrossRefGoogle Scholar
  3. Fischer J, Lefevre C, Morava E et al (2007) The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy. Nat Genet 39:28–30CrossRefGoogle Scholar
  4. Haemmerle G, Lass A, Zimmermann R et al (2006) Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science 312:734–737CrossRefGoogle Scholar
  5. Higashi M, Hirano K, Kobayashi K et al (2015) Distinct cardiac phenotype between two homozygotes born in a village with accumulation of a genetic deficiency of adipose triglyceride lipase. Int J Cardiol 192:30–32CrossRefGoogle Scholar
  6. Higashi M, Ikeda Y, Miyauchi H, Zaima N, Suzuki A, Li M, Kobayashi K, Naito H, Hirano K (2017) Imaging modalities for triglyceride deposit cardiomyovasculopathy. Ann Nucl Cardiol 3:94–102CrossRefGoogle Scholar
  7. Hirano K (2009) A novel clinical entity: triglyceride deposit cardiomyovasculopathy. J Atheroscler Thromb 16:702–705CrossRefGoogle Scholar
  8. Hirano K, Ikeda Y, Zaima N et al (2008) Triglyceride deposit cardiomyovasculopathy. N Engl J Med 359:2396–2398CrossRefGoogle Scholar
  9. Hirano K, Tanaka T, Ikeda Y et al (2014) Genetic mutations in adipose triglyceride lipase and myocardial up-regulation of peroxisome proliferated activated receptor-gamma in patients with triglyceride deposit cardiomyovasculopathy. Biochem Biophys Res Commun 443:574–579CrossRefGoogle Scholar
  10. Hirano K, Ikeda Y, Sugimura K et al (2015) Cardiomyocyte steatosis and defective washout of iodine-123-beta-methyl iodophenyl-pentadecanoic acid in genetic deficiency of adipose triglyceride lipase. Eur Heart J 36:580CrossRefGoogle Scholar
  11. Ikeda Y, Hirano K, Fukushima N et al (2014a) A novel type of human spontaneous coronary atherosclerosis with triglyceride deposition. Eur Heart J 35:875CrossRefGoogle Scholar
  12. Ikeda Y, Zaima N, Hirano K et al (2014b) Coronary triglyceride deposition in contemporary advanced diabetics. Pathol Int 64:325–335CrossRefGoogle Scholar
  13. Kaneko K, Kuroda H, Izumi R et al (2014) A novel mutation in PNPLA2 causes neutral lipid storage disease with myopathy and triglyceride deposit cardiomyovasculopathy: a case report and literature review. Neuromuscul Disord 24:634–641CrossRefGoogle Scholar
  14. Muggenthaler M, Petropoulou E, Omer S et al (2016) Whole exome sequence analysis reveals a homozygous mutation in PNPLA2 as the cause of severe dilated cardiomyopathy secondary to neutral lipid storage disease. Int J Cardiol 210:41–44CrossRefGoogle Scholar
  15. Pennisi EM, Arca M, Bertini E et al (2017) Neutral lipid storage diseases: clinical/genetic features and natural history in a large cohort of Italian patients. Orphanet J Rare Dis 12:90CrossRefGoogle Scholar
  16. Reilich P, Horvath R, Krause S et al (2011) The phenotypic spectrum of neutral lipid storage myopathy due to mutations in the PNPLA2 gene. J Neurol 258:1987–1997CrossRefGoogle Scholar
  17. Takagi A, Ikeda Y, Kobayashi K et al (2018) Newly developed selective immunoinactivation assay revealed reduction in adipose triglyceride lipase activity in peripheral leucocytes from patients with idiopathic triglyceride deposit cardiomyovasculopathy. Biochem Biophys Res Commun 495(1):646–651Google Scholar
  18. Zimmermann R, Strauss JG, Haemmerle G et al (2004) Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 306:1383–1386CrossRefGoogle Scholar
  19. Zimmermann R, Lass A, Haemmerle G et al (2009) Fate of fat: the role of adipose triglyceride lipase in lipolysis. Biochim Biophys Acta 1791:494–500CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Cardiovascular Medicine, Laboratory of Cardiovascular Disease, Novel, Non-invasive, and Nutritional Therapeutics (CNT), Graduate School of MedicineOsaka UniversitySuitaJapan
  2. 2.Department of PathologyNational Cerebral and Cardiovascular CenterOsakaJapan

Personalised recommendations