Can changes in plasma insulin concentration explain the variability in leptin response to weight loss in obese women with normal glucose tolerance?

The aim of this study was to test the hypothesis that the fall in circulati ng insulin concentration associated with moderate weight loss determines th e associated decrease in plasma leptin concentration. For this purpose, 12 healthy, nondiabetic, obese women were studied before and after an average weight loss of 9.5 kg (11.2% of initial body weight). Plasma leptin concent rations fell from a mean (+/-SE) value of 35 +/- 3 to 17 +/- 2 ng/mL (P < 0 .001) in association with the toss of weight. However, there was no correla tion between the decline in leptin concentration and the associated fall in weight, body mass index, fat mass, or percent body fat. Furthermore, no co rrelation was seen among changes in fasting plasma glucose or insulin conce ntrations, the 8-h integrated plasma glucose response to breakfast and lunc h, or the estimate of insulin-mediated glucose disposal. The only measured variable that correlated with the fall in plasma leptin concentration (r = 0.78; P < 0.005) was the decline in the 8-h integrated plasma insulin respo nse after weight loss (from 304 +/- 44 to 232 +/- 36 mu U/8 h.mL; P < 0.001 ). Finally, multivariate regression analysis, using various estimates of de gree of obesity, insulin resistance, integrated glucose response, and integ rated insulin response as dependent variables, indicated that only the insu lin response was independently related to the decrease in leptin concentrat ion (P = 0.035). The fall in integrated insulin response accounted for 66% of the variance in leptin concentrations after weight loss, and this was tr ue no matter what the estimate of change in degree of obesity. In addition to offering an explanation for the variance in postweight loss leptin conce ntrations, these data provide further evidence of the importance of ambient insulin concentrations in the regulation of plasma leptin concentrations.