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

OBJECTIVE: Leptin, a primarily adipose tissue-derived protein product of th e obesity (ob) gene, is an important regulator of energy metabolism. The st rong association between body fat mass and elevated circulating leptin leve ls in humans suggests that leptin resistance, rather than leptin production , may contribute to the development of obesity and associated disorders. Th e 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 d iseases, diabetes mellitus and malignant neoplasmas, and completed a detail ed lifestyle questionnaire. In addition, all participants completed a follo w-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 h ad higher circulating insulin levels than men in the lowest quintile (mean = 2.7 ng/ml). After adjustments for baseline age, weight, height, smoking s tatus, alcohol intake, and physical activity, each 10 ng/ml increase in pla sma 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 betwe en leptin level and weight gain was limited to men with a baseline body mas s index (BMI) of greater than or equal to 25 kg/m(2), in whom a 10ng/ml hig her baseline leptin was associated with a 2.45 kg (95% CI 0.73-4.18-kg) wei ght gain. Further adjustments for baseline total energy intake, plasma insu lin 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 concentration s among overweight men may be a marker of leptin resistance and subsequent weight gain.