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

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

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

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

⁵Department of Laboratory Medicine, Children's Hospital, Boston, MA, USA and Department of Pathology, Harvard Medical School, Boston, MA, USA

⁶Division of Biological Science, Harvard School Public Health, Boston, MA, USA

⁷Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA

Correspondence to: N-F Chu, Department of Community Medicine, Tri-Service General Hospital, National Defense Medical Center, PO Box 90048-509, Nei-Hu, Taipei, Taiwan, Republic of China. E-mail: chuepi@ndmctsgh.edu.tw

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.

International Journal of Obesity (2001) 25, 346-353

leptin; weight gain; men