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:

Plasma leptin concentrations and four-year weight gain among US men

International Journal of Obesity volume 25, pages 346–353 (2001)Cite this article

Abstract

OBJECTIVE: Leptin, a primarily adipose tissue-derived protein product of the obesity (ob) gene, is an important regulator of energy metabolism. The strong association between body fat mass and elevated circulating leptin levels in humans suggests that leptin resistance, rather than leptin production, may contribute to the development of obesity and associated disorders. The purpose of this study is to evaluate the relationship between circulating plasma leptin levels and regulation of body weight over time among US men.

DESIGN: Four-year prospective study.

SUBJECTS: A total of 247 men from the Health Professionals Follow-up Study, who at baseline (1994), were 47–64 y of age, were free of cardiovascular diseases, diabetes mellitus and malignant neoplasmas, and completed a detailed lifestyle questionnaire. In addition, all participants completed a follow-up questionnaire in 1998.

MEASUREMENTS: Baseline plasma leptin levels and 4-y weight change.

RESULTS: At the start of follow-up, men in the highest quintile for plasma leptin (mean=12.1 ng/ml) weighed more, were less physically active, and had higher circulating insulin levels than men in the lowest quintile (mean=2.7 ng/ml). After adjustments for baseline age, weight, height, smoking status, alcohol intake, and physical activity, each 10 ng/ml increase in plasma leptin concentration was associated with a 1.68 kg (95% CI 0.14–3.18 kg) weight gain over the 4-y follow-up period. The observed association between leptin level and weight gain was limited to men with a baseline body mass index (BMI) of ≥25 kg/m2, in whom a 10ng/ml higher baseline leptin was associated with a 2.45 kg (95% CI 0.73–4.18-kg) weight gain. Further adjustments for baseline total energy intake, plasma insulin and soluble tumor necrosis factor receptors levels did not appreciably alter these results. Plasma insulin level was not independently associated with subsequent weight gain.

CONCLUSION: These results suggest that elevated plasma leptin concentrations among overweight men may be a marker of leptin resistance and subsequent weight gain.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1

Similar content being viewed by others

References

  1. Garrow JS . Health implications of obesity. In: Obesity and related diseases Churchill Livingstone: London 1988 pp 1–16.

  2. Gidding SS . A perspective on obesity Am J Med Sci 1995 310 (Suppl 1): S68–71.

    Article  Google Scholar 

  3. Bray GA . Health hazards of obesity Endocrinol Metab Clin Nutr Am 1996 25: 907–919.

    Article  CAS  Google Scholar 

  4. Kannel WB, Wilson PW . An update on coronary risk factors. Med Clin Nutr Am 1995 79: 951–971.

    Article  CAS  Google Scholar 

  5. Rimm EB, Stampfer MJ, Giovannucci E et al. Body size and fat distribution as predictors of coronary heart disease among middle-aged and older US men Am J Epidemiol 1995 141: 1117–1127.

    Article  CAS  Google Scholar 

  6. Huang Z, Willett WC, Manson JE et al. Body weight, weight change, and risk for hypertension in women Ann Intern Med 1998 128: 81–88.

    Article  CAS  Google Scholar 

  7. Golay A, Felber JP . Evolution from obesity to diabetes Diabetes Metab 1994 20: 3–14.

    CAS  Google Scholar 

  8. 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.

    Article  CAS  Google Scholar 

  9. Ravussin E, Lillioja S, Knowler WC et al.Reduced rate of energy expenditure as a risk factor for body-weight gain New Engl J Med 1988 318: 467–472.

    Article  CAS  Google Scholar 

  10. Bouchard C, Tremblay A, Despres JP et al.The response to long-term overfeeding in identical twins New Engl J Med 1990 322: 1477–1482.

    Article  CAS  Google Scholar 

  11. Grundy SM . Multifactorial causation of obesity: implications for prevention Am J Clin Nutr 1998 67 (Suppl): 563S–572S.

    Article  CAS  Google Scholar 

  12. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM . Positional cloning of the mouse obese gene and its human homologue Nature 1994 372: 425–432.

    Article  CAS  Google Scholar 

  13. Pelleymounter MA, Cullen MJ, Baker MB et al. Effects of the obese gene product on body weight regulation in ob/ob mice Science 1995 269: 540–543.

    Article  CAS  Google Scholar 

  14. Halaas JL, Gajiwala KS, Maffer M et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995 269: 543–546.

    Article  CAS  Google Scholar 

  15. Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P . Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 1995 269: 546–549.

    Article  CAS  Google Scholar 

  16. Spiegelman BM, Flier JS . Adipogenesis and obesity rounding out the big picture Cell 1996 87: 377–389.

    Article  CAS  Google Scholar 

  17. Zimmet P, Hodge A, Nicolson M et al. Serum leptin concentration, obesity, and insulin resistance in Western Samoans cross sectional study Br Med J 1996 313: 965–969.

    Article  CAS  Google Scholar 

  18. Weigle DS . Leptin and other secretory products of adipocytes modulate multiple physiological functions Ann Endocrinol 1997 58: 132–136.

    CAS  Google Scholar 

  19. Flier JS . Clinical review 94: What's in a name? In search of leptin's physiologic role J Clin Endocrinol Metab 1998 83: 1407–1413.

    CAS  PubMed  Google Scholar 

  20. Friedman JM . Leptin, leptin receptors, and the control of body weight Nutr Rev 1998 56: s38–46.

    Article  CAS  Google Scholar 

  21. Auwerx J, Staels B . Leptin Lancet 1998 351: 737–742.

    Article  CAS  Google Scholar 

  22. Halaas JL, Boozer C, Blair-West J, Fidahusein N, Denton DA, Friedman JM . Physiological response to long-term peripheral and central leptin infusion in lean and obese mice Proc Natl Acad Sci USA 1997 94: 8878–8883.

    Article  CAS  Google Scholar 

  23. Caro JF, Kolaczynski JW, Nyce MR et al. Decreased cerebrospinal-fluid/serum leptin ratio in obesity. a possible mechanism for leptin resistance Lancet 1996 348: 159–161.

    Article  CAS  Google Scholar 

  24. Caro JF, Sinha MK, Kolaczynski JW, Zhang PL, Considine RV . Leptin: the tale of an obesity gene Diabetes 1996 45: 1455–1462.

    Article  CAS  Google Scholar 

  25. Maffei M, Stoffel M, Barone M et al. Absence of mutations in the human OB gene in obese/diabetic subjects. Diabetes 1996 45: 679–682.

    Article  CAS  Google Scholar 

  26. Carlsson B, Lindell K, Gabrielsson B et al. Obese (ob) gene defects are rare in human obesity. Obes Res 1997 5: 30–35.

    Article  CAS  Google Scholar 

  27. Considine RV, Sinha MK, Heiman ML et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. New Engl J Med 1996 334: 292–295.

    Article  CAS  Google Scholar 

  28. Hassink SG, Sheslow DV, de Lancey E, Opentanova I, Considine RV, Caro JF . Serum leptin in children with obesity, relationship to gender and development. Pediatrics 1996 98: 201–203.

    CAS  PubMed  Google Scholar 

  29. Haffner SM, Stern MP, Miettinen H, Wei M, Gingerich RL . Leptin concentrations in diabetic and nondiabetic Mexican-Americans Diabetes 1996 45: 822–824.

    Article  CAS  Google Scholar 

  30. Haffner SM, Gingerich RL, Miettinen H, Stem 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 

  31. Hamilton BS, Opaglia D, Kwan AY, Deitel M . Increased obese mRNA expression in omental fat cells from massively obese humans Nature Med 1995 1: 953–956.

    Article  CAS  Google Scholar 

  32. Lonnqvist F, Arner P, Nordfors L, Schalling M . Overexpression of the obese (ob) gene in adipose tissue of human obese subjects Nature Med 1995 1: 950–953.

    Article  CAS  Google Scholar 

  33. Maffei M, Halaas J, Ravussin E et al. Leptin levels in human and rodent measurement of plasma leptin and ob RNA in obese and weight-reduced subjects Nature Med 1995 1: 1155–1161.

    Article  CAS  Google Scholar 

  34. Arch JR, Stock MJ, Trayhurn P . Leptin resistance in obese humans: does it exist and what does it mean? Int J Obes Relat Metab Disord 1998 22: 1159–1163.

    Article  CAS  Google Scholar 

  35. Niskanen LK, Haffner S, Karhunen LJ, Turpeinen AK, Miettinen H, Uusitupa MI . Serum leptin in obesity is related to gender and body fat topography but does not predict successful weight loss Eur J Endocrinol 1997 137: 61–67.

    Article  CAS  Google Scholar 

  36. Ravussin E, Pratley RE, Maffei M et al. Relatively low plasma leptin concentrations precede weight gain in Pima Indians Nature Med 1997 3: 238–240.

    Article  CAS  Google Scholar 

  37. Lindroos AK, Lissner L, Carlsson B et al. Familial predisposition for obesity may modify the predictive value of serum leptin concentrations for long-term weight change in obese women Am J Clin Nutr 1998 67: 1119–1123.

    Article  CAS  Google Scholar 

  38. Haffner SM, Mykkanen LA, Gonzalez CC, Stern MP . Leptin concentrations do not predict weight gain the Mexico City Diabetes Study Int J Obes Relat Metab Disord 1998 22: 695–699.

    Article  CAS  Google Scholar 

  39. Rimm EB, Stampfer MJ, Colditz GA, Chute CG, Litin LB, Willett WC . Validity of self-reported waist and hip circumferences in men and women Epidemiology 1990 1: 466–473.

    Article  CAS  Google Scholar 

  40. National Heart Lung, and Blood Institute . Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. The evidence report NHLBI: Bethesda, MD 1998.

  41. Giovannucci E, Colditz G, Stampfer MJ et al. The assessment of alcohol consumption by a simple self-administered questionnaire Am J Epidemiol 1991 133: 810–817.

    Article  CAS  Google Scholar 

  42. Chasan-Taber S, Rimm EB, Stampfer MJ et al. Reproducibility and validity of a self-administered physical activity questionnaire for male health professionals. Epidemiology 1996 7: 81–86.

    Article  CAS  Google Scholar 

  43. Rimm EB, Giovannucci EL, Stampfer MJ, Colditz GA, Litin LB, Willett WC . Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals Am J Epidemiol 1992 135: 1114–1126. [Discussion 1127–1136.].

    Google Scholar 

  44. Chu NF, Makowski L, Hotamisligil GS, Rimm EB . Stability of human plasma leptin concentrations with 36 hours following specimen collection Clin Biochem 1999 32: 87–89.

    Article  CAS  Google Scholar 

  45. Ma Z, Gingerich RL, Santiago JV, Klein S, Smith CH, Landt M . Radioimmunoassay of leptin in human plasma Clin Chem 1996 42: 942–946.

    CAS  Google Scholar 

  46. Cusin I, Sainsbury A, Doyle P, Rohner-Jeanrenaud F, Jeanrenaud B . The ob gene and insulin. A relationship leading to clues to the understanding of obesity Diabetes 1995 44: 1467–1470.

    Article  CAS  Google Scholar 

  47. Mantzoros CS, Moschos S, Avramopoulos I et al. Leptin concentrations in relation to body mass index and the tumor necrosis factor-alpha system in humans J Clin Endocrinol Metab 1997 82: 3408–3413.

    CAS  PubMed  Google Scholar 

  48. Mantzoros CS, Liolios AD, Tritos NA et al. Circulating insulin concentrations, smoking, and alcohol intake are important independent predictors of leptin in young healthy men Obes Res 1998 6: 179–186.

    Article  CAS  Google Scholar 

  49. Wei M, Stern MP, Haffner SM . Serum leptin levels in Mexican Americans and non-Hispanic whites association with body mass index and cigarette smoking Ann Epidemiol 1997 7: 81–86.

    Article  CAS  Google Scholar 

  50. Hunter D . Biochemical indicators of dietary intake. In: Willett W (ed). Nutritional epidemiology 2nd edn New Oxford University, press, New York 1998 174–243.

    Google Scholar 

  51. Rosenbaum M, Nicolson M, Hirsch J et al. Effects of gender, body composition, and menopause on plasma concentrations of leptin J Clin Endocrinol Metab 1996 81: 3424–3427.

    CAS  PubMed  Google Scholar 

  52. Muller N, O'Brien P, Nair KS . Disruption of the relationship between fat content and leptin levels with aging in humans J Clin Endocrinol Metab 1998 83: 931–934.

    Google Scholar 

  53. Wing RR, Sinha MK, Considine RV, Lang W, Caro JF . Relationship between weight loss maintenance and changes in serum leptin levels Horm Metab Res 1996 28: 698–703.

    Article  CAS  Google Scholar 

  54. Howard BV, Bogardus C, Ravussin E et al. Studies of the etiology of obesity in Pima Indians Am J Clin Nutr 1991 53: 1577S–1585S.

    Article  CAS  Google Scholar 

  55. Reed DR, Ding Y, Xu W, Cather C, Green ED, Price RA . Extreme obesity may be linked to markers flanking the human OB gene Diabetes 1996 45: 691–694.

    Article  CAS  Google Scholar 

  56. Bouchard C . Genetics of human obesity: recent results from linkage studies J Nutr 1997 127: 1887S–1890S.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study is supported by research grant HL35464, CA55075 and AA11181. Dr Chu's work is supported by a Research Award from the National Defense Medical Center, Taiwan.

Author information

Authors and Affiliations

  1. Department of Epidemiology, Harvard School Public Health, Boston, MA, USA

    N-F Chu, D Spiegelman & EB Rimm

  2. Departments of Public Health and Community Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China

    N-F Chu

  3. Department of Biostatistics, Harvard School Public Health, Boston, MA, USA

    D Spiegelman

  4. Department of Nutrition, Harvard School Public Health, Boston, MA, USA

    J Yu, GS Hotamisligil & EB Rimm

  5. Department of Laboratory Medicine, Children's Hospital, Boston, MA, USA

    N Rifai

  6. Department of Pathology, Harvard Medical School, Boston, MA, USA

    N Rifai

  7. Division of Biological Science, Harvard School Public Health, Boston, MA, USA

    GS Hotamisligil

  8. Department of Medicine, Channing Laboratory, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA

    EB Rimm

Authors
  1. N-F Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D Spiegelman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N Rifai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. GS Hotamisligil
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. EB Rimm
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N-F Chu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chu, NF., Spiegelman, D., Yu, J. et al. Plasma leptin concentrations and four-year weight gain among US men. Int J Obes 25, 346–353 (2001). https://doi.org/10.1038/sj.ijo.0801549

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0801549

Keywords

This article is cited by

Search

Advanced search

Quick links