Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Communication
  • Published:

The impact of the leucine 7 to proline 7 polymorphism of the neuropeptide Y gene on postprandial lipemia and on the response of serum total and lipoprotein lipids to a reduced fat diet

Abstract

Objective: The aim of the study was to examine the impact of the leucine7 to proline7 (Leu7Pro) polymorphism of the NPY gene on postprandial (PP) lipemia, post-heparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities, and the response of serum lipids to a reduced fat diet.

Design and subjects: Seven middle-aged obese subjects with Leu7Pro genotype were matched with seven subjects with Leu7Leu genotype for gender, age, apolipoprotein E phenotype and BMI. These 14 subjects participated in the oral 8 h fat tolerance test. Sixty-eight slightly obese middle-aged subjects (10 with the Leu7Pro genotype) had participated in intervention studies and consumed a reduced fat diet for 8 weeks.

Results: There were no statistically significant differences in PP areas under the curve of plasma total triglycerides (TG), chylomicron TG, VLDL-TG or insulin between the genotype groups. The TG-to-cholesterol (C) ratio in VLDL was significantly lower in the subjects with Leu7Pro genotype compared to those with the Leu7Leu genotype at time points 30 min and 1 h in the fat tolerance test. Heparin-induced activities of LPL or HL or the response of serum total or LDL-C to the reduced fat diet did not differ between the groups.

Conclusions: The NPY genotype neither affects the magnitude of postprandial lipemia induced by a fat tolerance test nor the response of serum total lipids or lipids in different lipoprotein classes to the reduced fat diet. However, this preliminary study suggests that there might be compositional differences in the lipoprotein particles between the genotype groups that affect postprandial lipid metabolism.

Sponsorship: The Council for Health Sciences of the Academy of Finland, Kuopio University Hospital and the National Technology Agency, Finland.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  • Ågren JJ, Valve R, Vidgren H, Laakso M, Uusitupa M . 1998 Postprandial lipemic response is modified by the polymorphism at codon 54 of the fatty acid-binding protein 2 gene Arterioscler. Thromb. Vasc. Biol. 18: 1606–1610

    Article  Google Scholar 

  • Billington CJ, Briggs JE, Grace M, Levine AS . 1991 Effects of intracerebroventricular injection of neuropeptide Y on energy metabolism Am. J. Physiol. 260: R321–R327

    CAS  PubMed  Google Scholar 

  • Billington CJ, Briggs JE, Harker S, Grace M, Levine AS . 1994 Neuropeptide Y in hypothalamic paraventricular nucleus: a center coordinating energy metabolism Am. J. Physiol. 266: R1765–R1770

    CAS  PubMed  Google Scholar 

  • Björkegren J, Hamsten A, Milne RW, Karpe F . 1997 Alterations of VLDL composition during alimentary lipemia J. Lipid Res. 38: 301–314

    PubMed  Google Scholar 

  • Cohn JS, McNamara JR, Cohn SD, Ordovas JM, Schaefer EJ . 1988 Postprandial plasma lipoprotein changes in human subjects of different ages J. Lipid Res. 29: 469–479

    CAS  PubMed  Google Scholar 

  • Criscione L, Rigoller P, Batzl-Hartmann C, Rueger H, Stricker-Krongrad A, Wyss P, Brunner L, Whitebread S, Yamaguchi Y, Gerald C, Heurich RO, Walker MW, Chiesi M, Schilling W, Hofbauer KG, Levens N . 1998 Food intake in free-feeding and energy-deprived lean rats is mediated by the neuropeptide Y5 receptor J. Clin. Invest. 102: 2136–2145

    Article  CAS  Google Scholar 

  • Dietschy JM, Turley SD, Spady DK . 1993 Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans J. Lipid Res. 34: 1637–1659

    CAS  PubMed  Google Scholar 

  • Dueland S, France D, Wang SL, Trawick JD, Davis RA . 1997 Cholesterol 7alpha-hydroxylase influences the expression of hepatic apoA-I in two inbred mouse strains displaying different susceptibilities to atherosclerosis and in hepatoma cells J. Lipid Res. 38: 1445–1453

    CAS  PubMed  Google Scholar 

  • Ehnholm C, Kuusi T . 1986 Preparation, characterization, and measurement of hepatic lipase Meth. Enzymol. 129: 716–738

    Article  CAS  Google Scholar 

  • Ehnholm C, Lukka M, Kuusi T, Nikkilä E, Utermann G . 1986 Apolipoprotein E polymorphism in the Finnish population: gene frequencies and relation to lipoprotein concentrations J. Lipid Res. 27: 227–235

    CAS  PubMed  Google Scholar 

  • Frankish HM, Dryden S, Hopkins D, Wang Q, Williams G . 1995 Neuropeptide Y, the hypothalamus, and diabetes: insights into the central control of metabolism Peptides 16: 757–771

    Article  CAS  Google Scholar 

  • Gray TS, Morley JE . 1986 Neuropeptide Y: anatomical distribution and possible function in mammalian nervous system Nature 38: 389–401

    CAS  Google Scholar 

  • Hallikainen M, Uusitupa MIJ . 1999 Effects of 2 low-fat stanol ester-containing margarines on serum cholesterol concentrations as part of a low-fat diet in hypercholesterolemic subjects Am. J. Clin. Nutr. 69: 403–410

    Article  CAS  Google Scholar 

  • Karvonen MK, Pesonen U, Koulu M, Niskanen L, Laakso M, Rissanen A, Dekker JM, 'T Hart LM, Valve R, Uusitupa MIJ . 1998 Association of a leucine(7)-to-proline(7) polymorphism in the signal peptide of neuropeptide Y with high serum cholesterol and LDL cholesterol levels Nature Med. 4: 1434–1437

    Article  CAS  Google Scholar 

  • Karvonen MK, Koulu M, Pesonen U, Uusitupa MI, Tammi A, Viikari J, Simell O, Rönnemaa T . 2000 Leucine 7 to proline 7 polymorphism in the preproneuropeptide Y is associated with birth weight and serum triglyceride concentration in preschool aged children J. Clin. Endocrinol. Metab. 85: 1455–1460

    CAS  PubMed  Google Scholar 

  • Lundberg JM, Terenius L, Hökfelt T, Martling CR, Tatemoto K, Mutt V, Polak J, Bloom S, Goldstein M . 1982 Neuropeptide Y (NPY)-like immunoreactivity in peripheral noradrenergic neurons and effects of NPY on sympathetic function Acta Physiol. Scand. 116: 477–480

    Article  CAS  Google Scholar 

  • McMinn JE, Seeley RJ, Wilkinson CW, Havel PJ, Woods SC, Schwartz MW . 1998 NPY-induced overfeeding suppresses hypothalamic NPY mRNA expression: potential roles of plasma insulin and leptin Regul. Pept. 75–76: 425–431

    Article  Google Scholar 

  • Menzel H-J, Utermann G . 1986 Apolipoprotein E phenotyping from serum by Western blotting Electrophoresis 7: 492–495

    Article  CAS  Google Scholar 

  • Moltz JH, McDonald JK . 1985 Neuropeptide Y: direct and indirect action on insulin secretion in the rat Peptides 6: 1155–1159

    Article  CAS  Google Scholar 

  • Niskanen L, Karvonen MK, Valve R, Koulu M, Pesonen U, Mercuri M, Rauramaa R, Toyry J, Laakso M, Uusitupa MI . 2000 Leucine 7 to proline 7 polymorphism in the neuropeptide Y gene is associated with enhanced carotic athrosclerosis in elderly patients with type 2 diabetes and control subjects J. Clin. Endocrinol. Metab. 85: 2266–2269

    CAS  PubMed  Google Scholar 

  • Palmiter RD, Erickson JC, Hollopeter G, Baraban SC, Schwartz MW . 1998 Life without neuropeptide Y Recent Prog. Horm. Res. 53: 163–199

    CAS  PubMed  Google Scholar 

  • Penttilä IM, Voutilainen E, Laitinen O, Juutilainen P . 1981 Comparison of different analytical and precipitation methods for the direct estimation of high-density lipoprotein cholesterol Scand. J. Lab. Invest. 41: 353–360

    Article  Google Scholar 

  • Roche HM, Gibney MJ . 1995 Postprandial triacylglycerolaemia: nutritional implications Prog. Lipid Res. 34: 249–266

    Article  CAS  Google Scholar 

  • Sarkkinen E, Korhonen M, Erkkilä A, Ebeling T, Uusitupa M . 1998 Effect of apolipoprotein E polymorphism on serum lipid response to the separate modification of dietary fat and dietary cholesterol Am. J. Clin. Nutr. 68: 1215–1222

    Article  CAS  Google Scholar 

  • Stanley BG, Leibowitz SF . 1985 Neuropeptide Y injected in the paraventricular hypothalamus: a powerful stimulant of feeding behaviour Proc. Natl. Acad. Sci. USA 82: 3940–3943

    Article  CAS  Google Scholar 

  • Stricker-Krongrad A, Cumin F, Burlet C, Beck B . 1998 Hypothalamic neuropeptide Y and plasma leptin after long-term high-fat feeding in the rat Neurosci. Lett. 254: 157–160

    Article  CAS  Google Scholar 

  • Tomaszuk A, Simpson C, Williams G . 1996 Neuropeptide Y, the hypothalamus and the regulation of energy homeostasis Horm. Res. 46: 53–58

    Article  CAS  Google Scholar 

  • Uusitupa MIJ, Karvonen MK, Pesonen U, Koulu M . 1998 Neuropeptide Y: a novel link between the neuroendocrine system and cholesterol metabolism Ann. Med. 30: 508–510

    Article  CAS  Google Scholar 

  • Vettor R, Pagano C, Granzotto M, Englaro P, Angeli P, Blum WF, Federspil G, Rohner-Jeanrenaud F, Jeanrenaud B . 1998 Effects of intravenous neuropeptide Y on insulin secretion and insulin sensitivity in skeletal muscle in normal rats Diabetologia 41: 1361–1367

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors wish to thank laboratory nurses Kaija Kettunen, Erja Kinnunen, Irja Kanniainen and Ritva Nurmi for excellent technical assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to US Schwab.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schwab, U., Ågren, J., Valve, R. et al. The impact of the leucine 7 to proline 7 polymorphism of the neuropeptide Y gene on postprandial lipemia and on the response of serum total and lipoprotein lipids to a reduced fat diet. Eur J Clin Nutr 56, 149–156 (2002). https://doi.org/10.1038/sj.ejcn.1601297

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ejcn.1601297

Keywords

This article is cited by

Search

Quick links