Determinants of within-subject variation of fasting serum leptin concentrations in healthy subjects

The hormone leptin is considered to contribute to body weight regulation th rough modulation of feeding behavior and energy expenditure. The aim of the present study was 1) to assess the day-to-day within-subject variation (bi ovariability) of serum leptin concentrations in healthy subjects and 2) to investigate whether this variation is associated with food intake. exercise . anthropometric measurements or various metabolic covariates (insulin. C-p eptide and glucagon, glucose, lactate, 3-hydroxybutyrate (3-OHB). triglycer ides, non-esterified-fatty acids and glycerol). Serum leptin levels were ta ken daily on 12 consecutive days after an overnight fast in 12 healthy subj ects with a mean (SD) age of 22.7 (1.5) yr. and a BMI of 22.8 (1.6) kg/m(2) . Food intake, exercise, anthropometric measurements and various metabolic covariates were also determined during this period. The overall mean of serum leptin concentration was 33.3 pmol/L with a withi n-subject SD range of 27-41 pmol/L and a between-subject SD range of 18-61 pmol/L. The within-subject variance of serum leptin as a proportion of tota l variance was 9.5%. Within-subject variation of serum leptin concentration s is small in relation to between-subject variation in healthy, normal weig ht subjects. This has implications fur the power of interventional or prosp ective studies. In men. 6.7% of the variation in serum leptin concentration was associated with body weight measured on the same day (p=0.037). Tn wom en. however. 66% of the variation was negatively associated with 3-OHB meas ured on both the same and the previous day (p=0.0003 and 0.002), and positi vely associated with triglyceride concentration measured on the previous da y (p=0.0017) and insulin measured on the same day (p=0.0002). Within-subjec t associations in women could be due to phasic changes in unmeasured variab les, possibly related to the menstrual cycle or might suggest that energy b alance may exert a delayed influence on serum leptin levels. with plasma 3- OHB and triglycerides acting as markers for the state of the fat stores tha t regulate leptin secretion. The differences between the genders remain une xplained. however.