INCREASED PLASMA LEPTIN LEVELS ARE ASSOCIATED WITH FAT ACCUMULATION IN JAPANESE-AMERICANS

Although the hormone leptin seems to play a role in ensuring the maint enance of adequate energy stores and thereby protects against starvati on, its role in the regulation of body weight and adiposity under norm al circumstances is unclear. Overweight individuals have markedly elev ated circulating leptin levels, suggesting that leptin's effect on foo d intake and thermogenesis is diminished or absent in obesity. Recent evidence, though, indicates that weight gain in Pima Indians is associ ated with relatively decreased levels of the hormone. Because it is im portant to understand whether a deficiency in circulating leptin contr ibutes to the development of obesity, we sought to determine whether t here is a relationship between leptin levels and subsequent changes in adiposity in a more typical population. We compared baseline plasma l eptin concentrations to changes over 5 years in body weight, BMI, and computed tomography-determined total fat in 492 second-and third-gener ation Japanese Americans. Subjects were of 100% Japanese ancestry; mal e subjects had a mean BMI at baseline of 25.4 kg/m(2) and a mean age o f 54 years; female subjects had a mean BMI of 23.1 kg/m(2) 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 fo r 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 po pulation, fat accumulation is associated not with leptin deficiency bu t possibly with leptin resistance and is preceded by increased leptin levels.