Skip to main content Accessibility help
×
Home

A variant in the heart-specific fatty acid transport protein 6 is associated with lower fasting and postprandial TAG, blood pressure and left ventricular hypertrophy

  • Annegret Auinger (a1) (a2), Ulf Helwig (a3), Maria Pfeuffer (a2) (a4), Diana Rubin (a3), Mark Luedde (a5), Tim Rausche (a5), Nour Eddine El Mokhtari (a5), Ulrich R. Fölsch (a3), Stefan Schreiber (a3), Norbert Frey (a5) and Jürgen Schrezenmeir (a2) (a4) (a6)...

Abstract

Fatty acid transport protein 6 (FATP6) is primarily expressed in the heart and seems to be involved in cardiac fatty acid uptake. Therefore, we investigated whether a variation in the 5′-untranslated region of the FATP6 gene is associated with features of the metabolic syndrome and signs of myocardial alteration or heart failure. A total of 755 male participants from a Metabolic Intervention Cohort Kiel were genotyped for the FATP6–7T>A polymorphism (rs2526246) and phenotyped for features of the metabolic syndrome. Participants underwent a glucose tolerance test and the postprandial assessment of metabolic variables after a standardised mixed meal. Left ventricular heart function was evaluated in fifty-four participants. Fasting (P = 0·01) and postprandial (P = 0·02) TAG concentrations were significantly lower in AA homozygotes when compared with wild-type carriers. Homozygosity of allele A was associated with significantly lower postprandial insulin concentrations after a glucose load and significantly lower systolic (P = 0·01) and diastolic (P = 0·01) blood pressure values compared with wild-type carriers. Accordingly, left ventricular heart mass was significantly lower in twenty-seven AA homozygotes in comparison with twenty-seven TT homozygotes, matched for BMI (P = 0·04). In conclusion, the effects of the FATP6 polymorphism on TAG are mediated by affluent dietary fat. The FATP6–7T>A polymorphism may protect from traits of the metabolic syndrome and CVD.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      A variant in the heart-specific fatty acid transport protein 6 is associated with lower fasting and postprandial TAG, blood pressure and left ventricular hypertrophy
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      A variant in the heart-specific fatty acid transport protein 6 is associated with lower fasting and postprandial TAG, blood pressure and left ventricular hypertrophy
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      A variant in the heart-specific fatty acid transport protein 6 is associated with lower fasting and postprandial TAG, blood pressure and left ventricular hypertrophy
      Available formats
      ×

Copyright

Corresponding author

*Corresponding author: A. Auinger, fax +49 431 609 2472, email annegret.auinger@mri.bund.de

References

Hide All
1 Tamariz, L, Hassan, B, Palacio, A, et al. (2009) Metabolic syndrome increases mortality in heart failure. Clin Cardiol 32, 327331.
2 Ceriello, A, Taboga, C, Tonutti, L, et al. (2002) Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment. Circulation 106, 12111218.
3 Roman, MJ, Pickering, TG, Schwartz, JE, et al. (1995) Association of carotid atherosclerosis and left ventricular hypertrophy. J Am Coll Cardiol 25, 8390.
4 Levy, D, Garrison, RJ, Savage, DD, et al. (1990) Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 322, 15611566.
5 Stanley, WC, Recchia, FA & Lopaschuk, GD (2005) Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 85, 10931129.
6 Opie, LH (2004) The metabolic vicious cycle in heart failure. Lancet 364, 17331734.
7 van der Vusse, GJ, van Bilsen, M & Glatz, JFC (2000) Cardiac fatty acid uptake and transport in health and disease. Cardiovasc Res 45, 279293.
8 Gimeno, RE, Ortegon, AM, Patel, S, et al. (2003) Characterization of a heart-specific fatty acid transport protein. J Biol Chem 278, 1603916044.
9 Hajri, T, Ibrahimi, A, Coburn, CT, et al. (2001) Defective fatty acid uptake in the spontaneously hypertensive rat is a primary determinant of altered glucose metabolism, hyperinsulinemia, and myocardial hypertrophy. J Biol Chem 276, 2366123666.
10 Chiu, H-C, Kovacs, A, Blanton, RM, et al. (2005) Transgenic expression of fatty acid transport protein 1 in the heart causes lipotoxic cardiomyopathy. Circ Res 96, 225233.
11 Alberti, KG, Zimmet, P & Shaw, J (2006) Metabolic syndrome–a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med 23, 469480.
12 Rubin, D, Helwig, U, Nothnagel, M, et al. (2010) Association of postprandial and fasting triglycerides with traits of the metabolic syndrome in the Metabolic Intervention Cohort Kiel (MICK). Eur J Endocrinol 162, 719727.
13 Matthews, DR, Hosker, JP, Rudenski, AS, et al. (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412419.
14 Mari, A, Pacini, G, Murphy, E, et al. (2001) A model-based method for assessing insulin sensitivity from the oral glucose tolerance test. Diabetes Care 24, 539548.
15 Hampe, J, Shaw, SH, Saiz, R, et al. (1999) Linkage of inflammatory bowel disease to human chromosome 6p. Am J Hum Genet 65, 16471655.
16 Devereux, RB & Reichek, N (1977) Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. Circulation 55, 613618.
17 Barrett, JC, Fry, B, Maller, J, et al. (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21, 263265.
18 Wingender, E, Chen, X, Hehl, R, et al. (2000) TRANSFAC: an integrated system for gene expression regulation. Nucleic Acids Res 28, 316319.
19 Monzillo, LU & Hamdy, O (2003) Evaluation of insulin sensitivity in clinical practice and in research settings. Nutr Rev 61, 397412.
20 Morillas, P, Castillo, J, Quiles, J, et al. (2008) Usefulness of NT-proBNP level for diagnosing left ventricular hypertrophy in hypertensive patients. A cardiac magnetic resonance study. Rev Esp Cardiol 61, 972975.
21 Gilde, AJ & Van Bilsen, M (2003) Peroxisome proliferator-activated receptors (PPARS): regulators of gene expression in heart and skeletal muscle. Acta Physiol Scand 178, 425434.
22 Peterson, J, Bihain, BE, Bengtsson-Olivecrona, G, et al. (1990) Fatty acid control of lipoprotein lipase: a link between energy metabolism and lipid transport. Proc Natl Acad Sci U S A 87, 909913.
23 Goudriaan, JR, den Boer, MAM, Rensen, PCN, et al. (2005) CD36 deficiency in mice impairs lipoprotein lipase-mediated triglyceride clearance. J Lipid Res 46, 21752181.
24 Augustus, A, Yagyu, H, Haemmerle, G, et al. (2004) Cardiac-specific knock-out of lipoprotein lipase alters plasma lipoprotein triglyceride metabolism and cardiac gene expression. J Biol Chem 279, 2505025057.
25 Vedala, A, Wang, W, Neese, RA, et al. (2006) Delayed secretory pathway contributions to VLDL-triglycerides from plasma NEFA, diet, and de novo lipogenesis in humans. J Lipid Res 47, 25622574.
26 Steinberg, HO, Tarshoby, M, Monestel, R, et al. (1997) Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. J Clin Invest 100, 12301239.
27 Pedrini, MT, Kranebitter, M, Niederwanger, A, et al. (2005) Human triglyceride-rich lipoproteins impair glucose metabolism and insulin signalling in L6 skeletal muscle cells independently of non-esterified fatty acid levels. Diabetologia 48, 756766.
28 Yamauchi, T, Kamon, J, Waki, H, et al. (2001) The mechanisms by which both heterozygous peroxisome proliferator-activated receptor gamma (PPARgamma) deficiency and PPARgamma agonist improve insulin resistance. J Biol Chem 276, 4124541254.
29 Sundstrom, J, Lind, L, Vessby, B, et al. (2001) Dyslipidemia and an unfavorable fatty acid profile predict left ventricular hypertrophy 20 years later. Circulation 103, 836841.
30 Davila-Roman, VG, Vedala, G, Herrero, P, et al. (2002) Altered myocardial fatty acid and glucose metabolism in idiopathic dilated cardiomyopathy. J Am Coll Cardiol 40, 271277.
31 Heather, LC, Cole, MA, Lygate, CA, et al. (2006) Fatty acid transporter levels and palmitate oxidation rate correlate with ejection fraction in the infarcted rat heart. Cardiovasc Res 72, 430437.

Keywords

A variant in the heart-specific fatty acid transport protein 6 is associated with lower fasting and postprandial TAG, blood pressure and left ventricular hypertrophy

  • Annegret Auinger (a1) (a2), Ulf Helwig (a3), Maria Pfeuffer (a2) (a4), Diana Rubin (a3), Mark Luedde (a5), Tim Rausche (a5), Nour Eddine El Mokhtari (a5), Ulrich R. Fölsch (a3), Stefan Schreiber (a3), Norbert Frey (a5) and Jürgen Schrezenmeir (a2) (a4) (a6)...

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed