Leptin binds to the soluble form of its receptor (sOB-R). Leptin and sOB-R balance (free leptin index, FLI) reflect leptin activity. Leptin correlates with obesity and insulin resistance, but it remains uncertain whether sOB-R and FLI also do the same. Therefore, the aim of this study was to measure serum leptin, sOB-R, and FLI, and evaluate their associations with BMI and insulin resistance. We studied 145 obese and 49 nonobese humans. Obesity was defined according to WHO (BMI >30 kg/m (2)). Results are given as: median and interquartile range, obese vs. nonobese, respectively. Leptin (ng/ml): 30.83, 37.27 vs. 8.31, 10.04; sOB-R (ng/ml): 17.62, 17.05 vs. 27.25, 11.30; FLI: 231.2, 310.0 vs. 30.85, 27.77; HOMA: 5.99, 6.64 vs. 3.92, 4.52; p<0.001 for all. Serum leptin, sOB-R, and FLI did not correlate with insulin resistance separately in obese and nonobese humans. Leptin and FLI, but not sOB-R, were associated with insulin resistance in obese and nonobese subjects examined together. Leptin, sOB-R and FLI differed between obese and nonobese humans, and, except sOB-R, correlated with BMI. In piecewise linear regression, BMI threshold where leptin increased was 24.6 (r=0.5969, p=0.00016 and <0.00001). Leptin and its free index, but not sOB-R, correlate with BMI only in a mixed obese and nonobese human cohort, and not in isolated obese or nonobese groups. Moreover, BMI threshold where leptin starts to increase is 24.6 kg/m (2), which is lower than the cutoff for overweight. Under the conditions, metabolic abnormalities may occur in parallel to much lower BMI levels as expected so far.

Although concentrations of resistin differ between obese and non-obese humans, no relationship between resistin concentration and insulin resistance has been found. Correlations between resistin and BMI are present only in a mixed population but disappear in non obese and obese subjects when analyzed separately.

Concentrations of adiponectin were not correlated with levels of glycosylated hemoglobin in the diabetic and non-diabetic subjects examined.

Reduced serum levels of adiponectin in obesity and insulin resistance seem paradoxical, since adipose tissue is the only source of adiponectin, and reports on that subject are contradictory. The aim of this study was to investigate the concentrations of adiponectin in non-obese and obese normoglycemic humans, and to determine the correlation between adiponectin and HOMA index of insulin sensitivity. Based on the WHO definition of obesity, 145 obese subjects and 49 non-obese controls (aged 20-55 years) were studied. The serum adiponectin concentrations did not differ between subjects and controls (p=0.6398) and were not correlated with HOMA index (r=-0.0211; p=0.8048, and r=-0.0523; p=0.4757, for subjects and controls, respectively). Adiponectin was not correlated with HOMA index in females (r=-0.0521; p=0.6546, and r=-0.0825; p=0.3981, for female subjects and controls, respectively) as well as in males (r=0.0033; p=0.9791, and r=0.0123; p=0.9131, for male subjects and controls, respectively). These results lead to the conclusion that neither the concentrations of adiponectin differ between obese and non-obese humans, nor does any relationship between adiponectin concentration and insulin sensitivity exist.

The genetic background of obesity is under research. Obesity-related phenotype candidate genes include the gene encoding adiponectin (AdipoQ). In this study, exon 3 of the adiponectin gene was screened for the Y111 H (Tyr111His, or T415C, rs17366743) polymorphism, and adiponectin serum concentrations were measured in 206 obese subjects (110 women and 96 men, aged 50.5+/-16.9 years). Their BMI, % of body fat, plasma glucose, insulin, and glycosylated hemoglobin were measured. Adiponectin was determined by enzyme-linked immunosorbent assay. Genomic DNA was extracted from peripheral blood leukocytes. A fragment of exon 3 of the adiponectin gene was amplified in PCR and screened for the Y111 H polymorphism in SSCP analysis. Genetic screening revealed a different SSCP pattern in 2 subjects. Subsequent genotyping disclosed the TC genotype in both subjects, resulting in Y111 H heterozygote variant frequency of 0.01 in the whole cohort. Other results for SNP (single nucleotide polymorphism) positive and negative subjects were as follows, respectively: BMI (kg/m (2)) 39.95+/-9.83 vs. 38.12+/-8.56; waist circumference (cm) 122+/-18.4 vs.115+/-16; glucose (mmol/l) 7.51+/-1.86 vs. 5.56+/-0.74; HbA1c (%) 7.55+/-1.86 vs. 6.58+/-1.36; body fat (%) 51+/-2 vs. 44+/-10; plasma insulin (mU/l) 28.92+/-16.50 vs. 37.59+/-47.34; adiponectin (ng/ml) 1301+/-15.8 vs. 5682+/-4156. Due to a proportion of 2 vs. 204, statistical calculations were not possible. The Y111 H adiponectin gene variant is uncommon in Polish obese subjects. Although we observed low adiponectin concentrations in Y111 H SNP heterozygote carriers, this finding was not confirmed by statistics.