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:

Dietary and lifestyle factors in relation to plasma leptin concentrations among normal weight and overweight men

International Journal of Obesity volume 25, pages 106–114 (2001)Cite this article

Abstract

OBJECTIVE: Leptin, the product of the obesity (ob) gene, is a multi-functional polypeptide that is important in energy metabolism, which is strongly correlated with body fat mass and body mass index (BMI). In a recent prospective study, we found that leptin was positively associated with 4 y weight gain among overweight and obese men. This suggests that leptin resistance, marked by hyperleptinemia among obese subjects, may be an important marker for weight gain. The purpose of this study is to evaluate whether modifiable dietary and lifestyle factors are associated with plasma leptin concentrations among US men.

METHODS: We included 268 men aged 47–83 y (who were free of cardiovascular disease, diabetes mellitus and cancer, except nonmelanoma skin cancer) from the ongoing Health Professionals Follow-up Study. These subjects completed a detailed dietary and lifestyle questionnaire (including cigarette smoking, alcohol drinking and physical activity) and provided a fasting venous blood sample in 1994. All blood samples were stored in a deep freeze (−70°C) for 4–5 y before being analyzed. Plasma leptin concentrations were measured by radioimmunoassay.

RESULTS: Men in the highest quintile of plasma leptin (mean=14.4 ng/ml) weighed more, were less physically active, and had higher total and saturated fat and cholesterol intake than men in the lowest quintile (mean=3.0 ng/ml). Physical activity and current smoking were inversely associated with plasma leptin concentrations (P<0.001). A 20 MET difference in physical activity per week (equivalent to approximately 3 h of jogging) was associated with 0.38–0.58 ng/ml lower plasma leptin concentrations for normal weight and overweight men after adjusting for total energy and fat intake, BMI and other confounding variables. Total fat and monounsaturated fat intakes were positively associated with plasma leptin concentrations even after adjusting for BMI and other confounding variables; however, this association was limited to men of normal weight (BMI<25 kg/m2).

CONCLUSION: These data suggest that physical activity may be a significant determinant of plasma leptin concentrations in men. Increasing physical activity is associated with lower plasma leptin concentrations even after adjusting for BMI. Physical activity may lower leptin concentrations not only due to decreased body fat mass, but potentially through an increase in leptin sensitivity.

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

Similar content being viewed by others

References

  1. 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  PubMed  Google Scholar 

  2. 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  PubMed  Google Scholar 

  3. 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  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Caprio S, Tamborlane WV, Silver D et al. Hyperleptinemia: an early sign of juvenile obesity. Relations to body fat depots and insulin concentrations Am J Physiol 1996 271: E626–630.

    CAS  PubMed  Google Scholar 

  6. Campfield LA, Smith FJ, Burn P . The OB protein [leptin] pathway—a link between adipose tissue mass and central neural networks Horm Metab Res 1996 28: 619–632.

    Article  CAS  PubMed  Google Scholar 

  7. Bray GA, York DA . Clinical review 90: leptin and clinical medicine: a new piece in the puzzle of obesity J Clin Endocrinol Metab 1997 82: 2771–2776.

    Article  CAS  PubMed  Google Scholar 

  8. Woods SC, Seeley RJ, Porte D Jr, Schwartz MW . Signals that regulate food intake and energy homeostasis Science 1998 280: 1378–1383.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  10. Hirschberg AL . Hormonal regulation of appetite and food intake Ann Med 1998 30: 7–20.

    Article  CAS  PubMed  Google Scholar 

  11. 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 

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

    Article  CAS  PubMed  Google Scholar 

  13. Bray GA, York DA . The MONA LISA hypothesis in the time of leptin Recent Prog Horm Res 1998 53: 95–118.

    CAS  PubMed  Google Scholar 

  14. Chu NF, Spiegelman D, Yu J, Rifai N, Hotamisligil GS, Rimm EB . Plasma leptin concentrations and 4-year weight gain among US men Int J Obes Relat Metab Disord (in press).

  15. Racette SB, Kohrt WM, Landt M, Holloszy JO . Response of serum leptin concentrations to 7 d of energy restriction in centrally obese African Americans with impaired or diabetic glucose tolerance Am J Clin Nutr 1997 66: 33–37.

    Article  CAS  PubMed  Google Scholar 

  16. Wadden TA, Considine RV, Foster GD, Anderson DA, Sarwer DB, Caro JS . Short-and long-term changes in serum leptin dieting obese women: effects of calorie restriction and weight loss J Clin Endocrinol Metab 1998 83: 214–218.

    CAS  PubMed  Google Scholar 

  17. Kolaczynski JW, Considine RV, Ohannesian J et al. Responses of leptin to short-term fasting and refeeding in humans: a link with ketogenesis but not ketones themselves Diabetes 1996 45: 1511–1515.

    Article  CAS  PubMed  Google Scholar 

  18. Kolaczynski JW, Ohannesian JP, Considine RV, Marco CC, Caro JF . Response of leptin to short-term and prolonged overfeeding in humans J Clin Endocrinol Metab 1996 81: 4162–4165.

    CAS  PubMed  Google Scholar 

  19. Masuzaki H, Ogawa Y, Hosoda K, Kawada T, Fushiki T, Nakao K . Augmented expression of the obese gene in the adipose tissue from rats fed high-fat diet Biochem Biophys Res Commun 1995 216: 355–358.

    Article  CAS  PubMed  Google Scholar 

  20. Surwit RS, Petro AE, Parekh P, Collins S . Low plasma leptin in response to dietary fat in diabetes and obesity-prone mice Diabetes 1997 46: 1516–1520.

    Article  CAS  PubMed  Google Scholar 

  21. Ahren B, Mansson S, Gingerich RL, Havel PJ . Regulation of plasma leptin in mice: influence of age, high-fat diet, and fasting Am J Physiol 1997 273: R113–R120.

    CAS  PubMed  Google Scholar 

  22. Dreon DM, Frey-Hewitt B, Ellsworth N, Williams PT, Terry RB, Wood PD . Dietary fat:carbohydrate ratio and obesity in middle-aged men Am J Clin Nutr 1988 47: 995–1000.

    Article  CAS  PubMed  Google Scholar 

  23. George V, Tremblay A, Despres JP, Leblanc C, Bouchard C . Effect of dietary fat content on total and regional adiposity in men and women Int J Obes 1990 14: 1085–1094.

    CAS  PubMed  Google Scholar 

  24. Miller WC, Niederpruem MG, Wallace JP, Lindeman AK . Dietary fat, sugar, and fiber predict body fat content J Am Diet Assoc 1994 94: 612–615.

    Article  CAS  PubMed  Google Scholar 

  25. Willett WC . is dietary fat a major determinant of body fat? Am J Clin Nutr 1998 67: 556S–562S.

    Article  CAS  PubMed  Google Scholar 

  26. MacDougald OA, Hwang CS, Fan H, Lane MD . Regulated expression of the obese gene product (leptin) in white adipose tissue and 3T3-L1 adipocytes Proc Natl Acad Sci USA 1995 92: 9034–9037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Saladin R, De Vos P, Guerre-Millo M et al. Transient increase in obese gene expression after food intake or insulin administration Nature 1995 377: 527–529.

    Article  CAS  PubMed  Google Scholar 

  28. Jenkins AB, Markovic TP, Fleury A, Campbell LV . Carbohydrate intake and short-term regulation of leptin in humans Diabetologia 1997 40: 348–351.

    Article  CAS  PubMed  Google Scholar 

  29. Havel PJ, Kasim-Karakas S, Mueller W, Johnson PR, Gingerich RL, Stern JS . Relationship of plasma leptin to plasma insulin and adiposity in normal weight and overweight women: effects of dietary fat content and sustained weight loss J Clin Endocrinol Metab 1996 81: 4406–4413.

    CAS  PubMed  Google Scholar 

  30. Schrauwen P, van Marken Lichtenbelt WD, Westerterp KR, Saris WH . Effect of diet composition on leptin concentration in lean subjects Metabolism 1997 46: 420–424.

    Article  CAS  PubMed  Google Scholar 

  31. Kohrt WM . Landt M, Birge SJ Jr. Serum leptin levels are reduced in response to exercise training, but not hormone replacement therapy, in older women J Clin Endocrinol Metab 1996 81: 3980–3985.

    CAS  PubMed  Google Scholar 

  32. Perusse L, Collier G, Gagnon J et al. Acute and chronic effects of exercise on leptin levels in humans J Appl Physiol 1997 83: 5–10.

    Article  CAS  PubMed  Google Scholar 

  33. van Aggel-Leijssen DPC, van Baak MA, Tenenbaum R, Campfield LA, Saris WHM . Regulation of average 24h human plasma leptin level; the influence of exercise and physiological changes in energy balance Int J Obes Relat Metab Disord 1999 23: 151–159.

    Article  CAS  PubMed  Google Scholar 

  34. Pasman WJ, Westerterp-Plantenga MS . Saris WH. The effect of exercise training on leptin levels in obese males Am J Physiol 1998 274: E280–286.

    CAS  PubMed  Google Scholar 

  35. 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  PubMed  Google Scholar 

  36. 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  PubMed  Google Scholar 

  37. Department of Agriculture . Composition of foods: raw, processed and prepared, 1966–1991, Agricultural Handbook no. 8-128-21 series Washington DC US Government Printing Office 1992.

  38. Willett WC, Stampfer MJ . Total energy intake: Implications for epidemiological analysis Am J Epidemiol 1986 124: 17–27.

    Article  CAS  PubMed  Google Scholar 

  39. 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.

    Article  CAS  PubMed  Google Scholar 

  40. 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  PubMed  Google Scholar 

  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  PubMed  Google Scholar 

  42. 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  PubMed  Google Scholar 

  43. 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  PubMed  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  PubMed  Google Scholar 

  45. White H . A heteroskedasticity-consistent covariance matrix estimator and a direct test for heteroskedasticity Econometrica 1980 48: 817–838.

    Article  Google Scholar 

  46. Frederich RC, Hamann A, Anderson S, Lollmann B, Lowell BB, Flier JS . Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action Nature Med 1995 1: 1311–1314.

    Article  CAS  PubMed  Google Scholar 

  47. Christensen JO, Svendsen OL, Hassager C, Christiansen C . Leptin in overweight postmenopausal women: no relationship with metabolic syndrome X or effect of exercise in addition to diet Int J Obes Relat Metab Disord 1998 22: 195–199.

    Article  CAS  PubMed  Google Scholar 

  48. Ostlund RE Jr, Yang JW, Klein S, Gingerich R . Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates J Clin Endocrinol Metab 1996 81: 3909–3913.

    PubMed  Google Scholar 

  49. Weigle DS, Duell PB, Connor WE, Steiner RA, Soules MR, Kuijper JL . Effect of fasting, refeeding, and dietary fat restriction on plasma leptin levels J Clin Endocrinol Metab 1997 82: 561–565.

    CAS  PubMed  Google Scholar 

  50. Grace DM, Pederson L, Speechley KN, McAlpine D . A longitudinal study of smoking status and weight loss following gastroplasty in a group of morbidly obese patients Int J Obes 1990 14: 311–317.

    CAS  PubMed  Google Scholar 

  51. Lissner L, Bengtsson C, Lapidus L, Bjorkelund C . Smoking initiation and cessation in relation to body fat distribution based on data from a study of Swedish women Am J Public Health 1992 82: 273–275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Perkins KA . Metabolic effects of tobacco smoking J Appl Physiol 1992 72: 401–409.

    Article  CAS  PubMed  Google Scholar 

  53. Audrain JE, Klesges RC, DePue K, Klesges LM . The individual and combined effects of cigarette smoking and food on resting energy expenditure Int J Obes 1991 15: 813–821.

    CAS  PubMed  Google Scholar 

  54. Tremblay A, Wouters E, Wenker M, St-Pierre S, Bouchard C, Despres JP . Alcohol and a high-fat diet: a combination favoring overfeeding Am J Clin Nutr 1995 62: 639–644.

    Article  CAS  PubMed  Google Scholar 

  55. Suter PM, Schutz Y, Jequier E . The effect of ethanol on fat storage in healthy subjects New Engl J Med 1992 326: 983–987.

    Article  CAS  PubMed  Google Scholar 

  56. Colditz GA, Giovannucci E, Rimm EB et al. Alcohol intake in relation to diet and obesity in women and men Am J Clin Nutr 1991 54: 47–48.

    Article  Google Scholar 

Download references

Acknowledgements

This study is supported by research grants 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

    NF Chu, MJ Stampfer, D Spiegelman & EB Rimm

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

    NF Chu, MJ Stampfer, GS Hotamisligil & EB Rimm

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

    GS Hotamisligil

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

    D Spiegelman

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

    MJ Stampfer & EB Rimm

  8. Department of Community Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China

    NF Chu

Authors
  1. NF Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. MJ Stampfer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D Spiegelman
    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 NF Chu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chu, N., Stampfer, M., Spiegelman, D. et al. Dietary and lifestyle factors in relation to plasma leptin concentrations among normal weight and overweight men. Int J Obes 25, 106–114 (2001). https://doi.org/10.1038/sj.ijo.0801468

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0801468

Keywords

This article is cited by

Search

Advanced search

Quick links