AIM: To evaluate whether fat distribution plays a role in determining serum leptin concentrations. PATIENTS AND METHODS: One-hundred and forty-seven obese patients, 77 males and 70 females, aged 45.1 AE 13.2 y (mean AE s.d.; range 21 ± 73 y), with body mass index (BMI) ranging from 30 to 55 kgam 2 (mean 42.3 AE 5.9). Ultrasound assessment of the thickness of subcutaneous and preperitoneal fat was carried out and calculation of their ratio as abdominal fat index (AFI), waist ± hip ratio (WHR), body composition by bioelectrical impedance to evaluate the percentage of fat mass (FM%) and total amount of fat (FMKg) were also determined. Plasma leptin was measured by radio immuno assay (RIA). RESULTS: In the whole group of patients, serum leptin concentrations were 37.2 AE 18.4 ngaml (range 6 ± 101.3 ngaml); in spite of BMI values not being signi®cantly different, women had leptin values signi®cantly higher (47.4 AE 17.4 ngaml) (P`0.01) than males (28.1 AE 15.1 ngaml), also after correction for fat mass. The mean thickness of abdominal subcutaneous fat was 33.7 AE 12.9 mm and it was signi®cantly (P`0.001) higher in female (40.9 AE 10.6 mm) than in male (27.1 AE 11.2 mm) patients; preperitoneal thickness was 22.9 AE 7.1 mm, with signi®cantly (P`0.05) higher values in males (24.2 AE 6.8 mm) than in females (21.7 AE 7.3 mm). Accordingly, AFI (in all patients 0.84 AE 0.6) was signi®cantly higher in males (1.09 AE 0.6) than in females (0.56 AE 0.2). In the overall population, leptin concentrations were directly and signi®cantly related to subcutaneous but not preperitoneal fat; they showed a strong inverse relationship with AFI and WHR. When the results were evaluated dividing the patients according to gender, subcutaneous fat thickness showed a stronger association with leptin levels in males than in females, whereas no association was found with preperitoneal fat thickness. Leptin and AFI values were signi®cantly related only in men. WHR values were not correlated with leptin concentrations in either sex. When fat mass was added to the model, subcutaneous fat thickness, AFI and WHR remained independently associated with leptin concentrations. Age and diabetes did not in¯uence these measures. CONCLUSIONS: Fat distribution contributes to the variability in serum leptin in obese patients. In particular, subcutaneous abdominal fat is a determinant of leptin concentration, also independently of the amount of fat mass, whereas the contribution of preperitoneal visceral fat is not signi®cant.

OBJECTIVE: To study clinical, anthropometric and metabolic determinants of serum leptin concentrations in a series of patients with a wide range of obesity. SUBJECTS: 400 patients, 116 males and 284 females, aged 44 AE 12.3 years with body mass index (BMI) ranging from 31 to 82 kgam 2 (mean 41.4 AE 7.1). MEASUREMENTS: Energy intake by 7-day recall, resting energy expenditure (REE) by indirect calorimetry, body composition determined by bioelectrical impedance; C index, an anthropometric index of abdominal fat distribution, and waist ± hip ratio (WHR), blood glucose serum leptin concentrations, total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, uric acid, and insulin concentrations HOMA IRI (homeostastis model assessment of insulin resistance index). RESULTS: Leptin concentrations were higher in obese than in normal subjects and in females than in males without differences between diabetic and non-diabetic patients; leptin concentrations were not related to age and showed a strong negative association with energy intake only in the group of women with BMI less than 40. Leptin concentrations showed a direct correlation with BMI and body fat values (expressed either as percentage of total body mass or absolute fat mass) independent of age and sex. After adjustment for fat mass, leptin values higher than predicted were found in women whereas concentrations lower than predicted were found predominantly in men. Leptin showed an inverse correlation with WHR and C-index, the latter persisting also after correction for gender and fat mass. REE, but not REEakg fat-free mass (FFM) was inversely related to leptin also after correction for sex and absolute fat mass. Leptin concentrations were directly associated with HOMA IRI, insulin and HDL cholesterol and inversely associated with triglycerides and uric acid. The relationship of leptin with HOMA IRI was still evident after adjusting for sex but was lost when absolute fat mass was added to the model; HDL cholesterol and triglycerides appeared to be variables independent of leptin concentrations even when both sex and fat mass were added to the model. CONCLUSIONS: In a large group of obese patients (half of whom had severe obesity, gender, BMI and fat mass accounted for the largest proportion of serum leptin concentrations variability. We found that in obese subjects there is an effect of fat distribution on leptin concentrations and that, after excluding variability due to absolute fat mass, patients with a greater amount of abdominal fat have relatively low leptin concentrations which in turn relates to a metabolic pro®le compatible with an increased cardiovascular risk. Women with milder obesity may retain some degree of control of food intake by leptin.