Fasting insulin levels influence plasma leptin levels independently from the contribution of adiposity: Evidence from both a cross-sectional and an intervention study

The aim of the present investigation was to determine whether leptinemia is only a reflection of the status of fat stores or if insulinemia has a sign ificant influence over leptin levels. Study 1 focused on the association between fasting plasma insulin and lepti n in subjects of the Quebec Family Study who were first classified as eithe r high- or low-insulin individuals and were then individually matched on th e basis of fat mass (FM). In Study 2, 19 men and 23 women took part in a 15 -week weight loss program that consisted of drug therapy (fenfluramine, 60 mg/day) or placebo coupled to an energy-restricted diet (-2930 kJ/day). Bod y weight, FM, and fat-free mass (assessed by underwater weighing) as well a s visceral and sc abdominal and mid-thigh adipose tissue measured by comput ed tomography were assessed before and after weight loss. Blood samples wer e drawn and analyzed for fasting plasma insulin and leptin before and after weight loss. In Study 1, significant positive associations were noted between log,, tran sformed fasting insulin and leptin in both men (r = 0.55, P < 0.0001) and w omen (r = 0.48, P < 0.0001). Moreover, after having carefully matched high- insulin to low-insulin individuals on the basis of FM, significantly lower leptin levels were observed in the low-insulin groups, in men (5.5 vs. 8.1 ng/mL, P < 0.05) as well as in women (18.7 vs. 24 ng/mL, P < 0.05). Results from Study 2 showed significant reductions of body weight, FM, fat-free ma ss, visceral abdominal tissue, sc abdominal tissue, and mid-thigh adipose t issue levels in men and women in response to the weight loss protocol. More over, the decrease in fasting plasma insulin was the only significant corre late of changes in fasting plasma leptin levels during weight loss, even af ter corrections for changes in FM in both men (r = 0.50, P < 0.05) and wome n (r = 0.46, P < 0.05). These results suggest that in a population characterized by a wide range of adiposity hyperinsulinemia has the potential to modulate leptin levels bey ond what can be explained by total adiposity. Moreover, this relation also seems to exist in a dynamic setting (i.e. during weight loss) because chang es in insulin were independent predictors of the changes in leptinemia in b oth men and women after correction for changes in FM.