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.

  • Paper
  • Published:

Association of leptin levels with obesity and blood pressure: possible common genetic variation

An Erratum to this article was published on 15 March 2005

Abstract

OBJECTIVE:

To ascertain the extent to which relationships between obesity (OB) and blood pressure (BP) can be explained by an individual's leptin plasma levels.

DESIGN:

Pedigree-based cross-sectional study in an apparently healthy population of European origin.

SUBJECTS:

The study sample is comprised of 90 nuclear and more complex families totaling 210 male and 213 female subjects aged 18–75 y, randomly recruited in Bashkorstan Autonomic region, Russia.

MEASUREMENTS:

Various fatness and fat distribution traits (including nine circumferences (CRCs), and eight skinfolds (CKFs) by anthropometry), blood pressure, and plasma leptin levels (by ELISA kits).

RESULTS:

Adjustment for circulating leptin led to attenuation of the magnitude of correlations between OB and BP, regardless of trait pair and sex cohort. Some of these correlations became statistically nonsignificant. All familial effects were gone, and heritability estimates became virtually zero after adjustment of each of the OB traits and systolic blood pressure (SBP) in offspring for leptin values in parents.

CONCLUSION:

BP and OB covariation is substantially mediated by circulating leptin levels. As a result, body fat has only a weak independent effect on BP variation after adjustment for leptin levels. Our findings also strongly suggest that genetic variation in body mass index, SKFs, and even body CRCs, as well as of SBP is due to genetic variation of leptin. Genetic variation of diastolic blood pressure in the present sample, however, shared very little with that of leptin.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Friedrich MJ . Epidemic of obesity expands its spread to developing countries. JAMA 2002; 287: 1382–1386.

    Article  CAS  PubMed  Google Scholar 

  2. Flegal KM, Carroll MD, Kuczmarski RJ, Johnson CL . Overweight and obesity in the United States: prevalence and trends, 1960–1994. Int J Obes Relat Metab Disord 1998; 22: 39–47.

    CAS  PubMed  Google Scholar 

  3. Froguel P, Boutin P . Genetics of pathways regulating body weight in the development of obesity in humans. Exp Biol Med 2001; 226: 991–996.

    Article  CAS  Google Scholar 

  4. Lean MEJ, Hans TS, Seidell JC . Impairment of health and quality of life in people with large waist circumference. Lancet 1998; 351: 853–856.

    Article  CAS  PubMed  Google Scholar 

  5. Kopelman PG . Obesity as a medical problem. Nature 2000; 404: 635–643.

    Article  CAS  PubMed  Google Scholar 

  6. Hofbauer KG . Molecular pathways to obesity. Int J Obes Relat Metab Disord 2002; 26 (Suppl 2): S18–S27.

    Article  CAS  PubMed  Google Scholar 

  7. Sader S, Nian M, Liu P . Leptin: a novel link between obesity, diabetes, cardiovascular risk, and ventricular hypertrophy. Circulation 2003; 108: 644–646.

    Article  PubMed  Google Scholar 

  8. Friedman JM, Halaas JL . Leptin and the regulation of body weight in mammals. Nature 1998; 395: 763–770.

    Article  CAS  PubMed  Google Scholar 

  9. Ahima RS, Flier JS . Leptin. Annu Rev Physiol 2001; 62: 413–437.

    Article  Google Scholar 

  10. Ruhl CE, Everhart JE . Leptin concentrations in the United States: relations with demographic and anthropometric measures. Am J Clin Nutr 2001; 74: 295–301.

    Article  CAS  PubMed  Google Scholar 

  11. Liuzzi A, Savia G, Tagliaferri M, Lucantoni R, Berselli ME, Petroni ML, De Medici C, Viberti GC . Serum leptin concentration in moderate and severe obesity: relationship with clinical, anthropometric and metabolic factors. Int J Obes Relat Metab Disord 1999; 23: 1066–1073.

    Article  CAS  PubMed  Google Scholar 

  12. Kaprio J, Eriksson J, Lehtovirta M, Koskenvuo M, Tuomilehto J . Heritability of leptin levels and the shared genetic effects on body mass index and leptin in adult Finnish twins. Int J Obes Relat Metab Disord 2001; 25: 132–137.

    Article  CAS  PubMed  Google Scholar 

  13. Livshits G, Pantsulaia I, Trofimov S, Kobyliansky E . Genetic variation of circulating leptin is involved in genetic variation of hand bone size and geometry. Osteoporos Int 2003; 14: 476–483.

    Article  CAS  PubMed  Google Scholar 

  14. Barba G, Russo O, Siani A, Iacone R, Farinaro E, Gerardi MC, Russo P, Della Valle E, Strazzullo P . Plasma leptin and blood pressure in men: graded association independent of body mass and fat pattern. Obes Res 2003; 11: 160–166.

    Article  PubMed  Google Scholar 

  15. Chu NF, Wang DJ, Shieh SM . Obesity, leptin and blood pressure among children in Taiwan: the Taipei Children's Heart Study. Am J Hypertens 2001; 14: 135–140.

    Article  CAS  PubMed  Google Scholar 

  16. Guagnano MT, Manigrasso MR, Ballone E, Della Vecchia R, Riccioni G, Marinopiccoli M, Nutini M, Sensi S, Davi G . Association between serum leptin levels and 24-hour blood pressure in obese women. Obes Res 2003; 11: 549–555.

    Article  PubMed  Google Scholar 

  17. El-Gharbawy AH, Kotchen JM, Grim CE, Kaldunski M, Hoffmann RG, Pausova Z, Hamet P, Kotchen TA . Gender-specific correlates of leptin with hypertension-related phenotypes in African Americans. Am J Hypertens 2002; 15: 989–993.

    Article  CAS  PubMed  Google Scholar 

  18. Henriksen JH, Holst JJ, Moller S, Andersen UB, Bendtsen F, Jensen G . Elevated circulating leptin levels in arterial hypertension: relationship to arteriovenous overflow and extraction of leptin. Clin Sci (Lond) 2000; 99: 527–534.

    Article  CAS  Google Scholar 

  19. Livshits G, Karasik D, Kobyliansky E . Complex segregation analysis of the radiographic phalanges bone mineral density and their age-related changes. J Bone Miner Res 2002; 17: 152–161.

    Article  PubMed  Google Scholar 

  20. Perloff D, Grim C, Flack J, Frohlich ED, Hill M, McDonald M, Morgenstern BZ . Human blood pressure determination by sphygmomanometry. Circulation 1993; 88: 2460–2470.

    Article  CAS  PubMed  Google Scholar 

  21. Livshits G, Yakovenko K, Ginsburg E, Kobyliansky E . Genetics of human body size and shape: pleiotropic and independent genetic determinants of adiposity. Ann Hum Biol 1998; 25: 221–236.

    Article  CAS  PubMed  Google Scholar 

  22. Lange K, Weeks D, Boehnke M . Program for Pedigree analysis: MENDEL, FISHER and dGENE. Genet Epidemiol 1988; 5: 471–472.

    Article  CAS  PubMed  Google Scholar 

  23. Sokal RR, Rohlf FJ . Biometry: the principles and practice of statistics in biological research, 3rd edn. W. H. Freeman and Co.: New York; 1995. pp 371–395.

    Google Scholar 

  24. Malkin I, Ginsburg E . Program package for Mendelian analysis of pedigree data (MAN, Version 5), Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University. Technical Report. 2003.

  25. Pantsulaia I, Trofimov S, Kalichman L, Kobyliansky E, Livshits G . The contribution of familial resemblance to variation in circulatory levels of tissue inhibitors of metalloproteinases and transforming growth factor-beta1. Calcif Tissue Int 2004; 74: 47–54.

    Article  CAS  PubMed  Google Scholar 

  26. Falconer DS, Mackay TF . Introduction to quantitative genetics, 4th edn. Longman, England, London; 1996.

    Google Scholar 

  27. Livshits G Vainder M, Blettner M, Graff E, Wahrendorf J, Brunner D . Major locus influencing plasma APO-A1 levels also controls plasma HDL3-C concentrations. Genet Epidemiol 1998; 15: 237–249.

    Article  PubMed  Google Scholar 

  28. Haffner SM, Gingerich RL, Miettinen H, Stern MP . Leptin concentrations in relation to overall adiposity and regional body fat distribution in Mexican Americans. Int J Obes Relat Metab Disord 1996; 20: 904–908.

    CAS  PubMed  Google Scholar 

  29. Ruige JB, Dekker JM, Blum WF, Stehouwer CD, Nijpels G, Mooy J, Kostense PJ, Bouter LM, Heine RJ . Leptin and variables of body adiposity, energy balance, and insulin resistance in a population-based study. The Hoorn Study. Diabetes Care 1999; 22: 1097–1104.

    Article  CAS  PubMed  Google Scholar 

  30. Hu FB, Chen C, Wang B, Stampfer MJ, Xu X . Leptin concentrations in relation to overall adiposity, fat distribution, and blood pressure in a rural Chinese population. Int J Obes Relat Metab Disord 2001; 25: 121–125.

    Article  CAS  PubMed  Google Scholar 

  31. Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds J . Identification and expression cloning of a leptin receptor, OB-R. Cell 1995; 83: 1263–1271.

    Article  CAS  PubMed  Google Scholar 

  32. Fruhbeck G . Pivotal role of nitric oxide in the control of blood pressure after leptin administration. Diabetes 1999; 48: 903–908.

    Article  CAS  PubMed  Google Scholar 

  33. Barouch LA, Berkowitz DE, Harrison RW, O'Donnell CP, Hare JM . Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice. Circulation 2003; 108: 754–759.

    Article  CAS  PubMed  Google Scholar 

  34. Jenkins AB, Samaras K, Gordon MA, Snieder H, Spector, Campbell LV . Lack of heritability of circulating leptin concentration in humans after adjustment for body size and adiposity using a physiological approach. Int J Obes Metab Disord 2001; 25: 1625–1632.

    Article  CAS  Google Scholar 

  35. Luke A, Guo X, Adeyemo AA, Wilks R, Forrester T, Lowe Jr W, Comuzzie AG, Martin LJ, Zhu X, Rotimi CN, Cooper RS . Heritability of obesity-related traits among Nigerians, Jamaicans and US black people. Int J Obes Relat Metab Disord 2001; 25: 1034–1041.

    Article  CAS  PubMed  Google Scholar 

  36. Feitosa MF, Borecki IB, Rich SS, Arnett DK, Sholinsky P, Myers RH, Leppert M, Province MA . Quantitative-trait loci influencing body-mass index reside on chromosomes 7 and 13: the National Heart, Lung, and Blood Institute Family Heart Study. Am J Hum Genet 2002; 70: 72–82.

    Article  CAS  PubMed  Google Scholar 

  37. Snieder H, Harshfield GA, Treiber FA . Heritability of blood pressure and hemodynamics in African- and European-American youth. Hypertension 2003; 41: 1196–1201.

    Article  CAS  PubMed  Google Scholar 

  38. North KE, Howard BV, Welty TK, Best LG, Lee ET, Yeh JL, Fabsitz RR, Roman MJ, MacCluer JW . Genetic and environmental contributions to cardiovascular disease risk in American Indians: the Strong Heart Family Study. Am J Epidemiol 2003; 157: 303–314.

    Article  PubMed  Google Scholar 

  39. Livshits G, Gerber LM . Familial factors of blood pressure and adiposity covariation. Hypertension 2001; 37: 928–935.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported jointly by the Israel National Science Foundation to GL (Grant # 544/00-1) and by a Postdoctoral Fellowship Grant (PI) kindly provided by UNESCO and Israel (the Ministry of Education, the Council for Higher Education's Planning and Budgeting Committee, the Ministry of Foreign Affairs and the Israel National Commission for UNESCO).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to G Livshits.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Livshits, G., Pantsulaia, I. & Gerber, L. Association of leptin levels with obesity and blood pressure: possible common genetic variation. Int J Obes 29, 85–92 (2005). https://doi.org/10.1038/sj.ijo.0802826

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0802826

Keywords

This article is cited by

Search

Quick links