Although the hormone leptin seems to play a role in ensuring the maintenance of adequate energy stores and thereby protects against starvation, its role in the regulation of body weight and adiposity under normal circumstances is unclear. Overweight individuals have markedly elevated circulating leptin levels, suggesting that leptin's effect on food intake and thermogenesis is diminished or absent in obesity. Recent evidence, though, indicates that weight gain in Pima Indians is associated with relatively decreased levels of the hormone. Because it is important to understand whether a deficiency in circulating leptin contributes to the development of obesity, we sought to determine whether there is a relationship between leptin levels and subsequent changes in adiposity in a more typical population. We compared baseline plasma leptin concentrations to changes over 5 years in body weight, BMI, and computed tomography-determined total fat in 492 second- and third-generation Japanese Americans. Subjects were of 100% Japanese ancestry; male subjects had a mean BMI at baseline of 25.4 kg/m2 and a mean age of 54 years; female subjects had a mean BMI of 23.1 kg/m2 and a mean age of 53 years. Changes in weight (men: r = 0.17, P < 0.05; women: r = 0.20, P < 0.05), BMI (men: r = 0.17, P < 0.05; women: r = 0.18, P < 0.05), and total fat (men: r = 0.19, P < 0.05; women: r = 0.20, P < 0.01) were positively correlated with baseline leptin levels adjusted for baseline adiposity, fasting insulin, and age. In Japanese Americans, then, relatively increased leptin levels are associated with greater subsequent gains in weight and adiposity. We concluded that in this population, fat accumulation is associated not with leptin deficiency but possibly with leptin resistance and is preceded by increased leptin levels.

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