Objective: The adipose-borne hormone leptin circulates in free and protein-bound forms but little information is available about their biological significance. Free leptin (FL) levels are related to changes in fat mass, whereas bound leptin (BL) appears to be associated with resting energy expenditure (REE). Our aim was to assess FL and BL levels in normal weight and obese subjects and correlate them with metabolic and nutritional variables.
Design and patients: The partitioning of plasma leptin between FL and BL was evaluated in a population (n = 44) including both genders and different degrees of adiposity [body mass index (BMI) range 18.6-79.6 kg/m2].
Measurements: Total leptin and FL and BL concentrations were measured by fast protein liquid chromatography (FPLC) followed by radioimmunoassay (RIA). Body composition, REE, insulin sensitivity, lipid parameters associated with cardiovascular risk and macronutrient preference were also assessed.
Results: The BL/FL ratio was significantly reduced in obese subjects due to a major increase in FL compared with BL. Consequently, the gender difference of the %BL/%FL ratio present in lean subjects (35/65 in women; 65/35 in men) was lost in obese subjects. REE was negatively correlated with total leptin (P < 0.0001) and %FL (P < 0.0001), and positively with %BL (P < 0.001). Total leptin and FL were correlated with the diet carbohydrate content in all subjects.
Conclusions: FL increases with the amount of fat mass; the prevalence of FL in normal weight women in comparison to men suggests that this fraction is particularly linked to the amount of subcutaneous fat. Moreover, the correlation of BL with REE and the relationship of FL with food intake favours the view of different biological activities for the two circulating forms of leptin.