Leptin or obesity receptor (Ob-R) is a member of class I cytokine receptor family. Ob-R, expressed in six isoforms, is the product of alternative RNA splicing of db gene. According to its structural differences, the receptor's isoforms are divided into three classes: long, short, and secretory isoforms. A long, fully active isoform of Ob-Rb is expressed mainly in the hypothalamus, where it takes part in energy homeostasis and in the regulation of secretory organs' activity. Ob-Rb is also present on all types of immune cells, involved in innate and adaptive immunity. Short leptin isoforms (Ob-Ra, Ob-Rc, Ob-Rd, and Ob-Re) that contain box 1 motif are able to bind JAK kinases (Janus kinases) as well as to activate some other signal transduction cascades. A soluble isoform (Ob-Re) can regulate serum leptin concentration and serve as a carrier protein delivering the hormone to its membrane receptors and is able to transduce the signal into the cell. JAK/STAT pathway plays the major role in leptin signal transduction through membrane receptors. Among all Ob-R isoforms, only full-length isoform (Ob-Rb) is able to fully transduce activation signal into the cell.

The adipose tissue has been recognized as an active organ involved in numerous metabolic, hormonal and immunological processes. Obesity and associated chronic inflammation leads to many metabolic and autoimmune disorders. The number of cells, their phenotype and distribution in adipose tissue depends on the degree of obesity. Polarization of macrophages towards M1, neutrophils influx to adipose tissue, activation of Th1 and Th17 cells and increased level of proinflammatory cytokines are characteristic for obesity-induced inflammation. Several mechanisms, such as adipocytes’ hypoxia, oxidative stress, endoplasmic reticulum stress, impairment of PPAR receptors, inflammasomes’ activation and activation of TLR are involved into development of chronic obesity-induced inflammation. A better understanding of this processes can provide new treatments for obesity and related disorders.

Forkhead box P3 (Foxp3) is an important regulatory factor for the development and function of T regulatory (Treg) cells. Moreover, it has been established that deficiency of the Foxp3 gene in Treg cells suppresses their regulatory function leading to the development of autoimmune diseases especially autoimmune thyroid diseases. The aim of our study was to estimate the association of three polymorphism of FOXP3 gene with the predisposition to Graves' disease (GD) and Hashimoto's thyroiditis (HT) in children and adolescents. The study was performed in the group consisting of 145 patients with GD (mean age, 16.5 ± 2 years), 87 patients with HT (mean age, 15.2 ± 2.2 years) sequentially recruited from the endocrinology outpatient clinic and 161 healthy volunteers (mean age, 16.3 ± 3 years). DNA was extracted from the peripheral blood leukocytes using a classical salting-out method. The three single nucleotide polymorphisms (SNPs) rs3761549 (-2383C/T), rs3761548 (-3279G/T) and rs3761547 (-3499T/C) in the FOXP3 gene were genotyped by TaqMan SNP genotyping assay using the real-time PCR method. The levels of thyroid hormones, TSH and anti-thyroid autoantibody were determined using chemiluminescence method. In our study, rs3761549G/A genotype was more frequent in female patients with GD in comparison to healthy female (15% vs. 7%, p = 0.033) with OR = 2.15 and 95% confidence interval for OR: 1.07-4.63. We have also observed rs3761547T/C to be more frequent in females with GD in comparison to control females, and this difference was close to statistically important (13% vs. 7%, p = 0.066) with OR = 1.99 and 95% confidence interval for OR: 0.96-4.48. There were no significant differences in males in analyzed SNPs and in females with rs3761548 SNP. In conclusion, these results may suggest that rs3761549G/A polymorphism in Foxp3 gene could contribute to GD development in females.

Obesity and thyroid function are closely related. Thyroid hormones are involved in the regulation of metabolism, thermogenesis, food intake, and fat oxidation. In obese children the most frequent hormonal abnormalities are slight hyperthyrotropinaemia and moderate increases in total T3 and/or fT3 concentrations. Those abnormalities are usually considered a cause of obesity, but according to recent studies, they should actually be considered an adaptation process aimed at increasing resting energy expenditure and total energy expenditure. Those abnormalities do not require any treatment and normalise after substantial weight loss. The mechanisms of those changes are dependent on leptin, thyroid hormone resistance, and mitochondrial dysfunction. The present paper describes the abovementioned mechanisms based on the latest research. We also present a review of some recent original studies evaluating thyroid function in overweight and obese children, including thyroid ultrasound. A thyroid ultrasound scan in obese children frequently shows increased thyroid volume, which correlates with moderately increased TSH levels and a hypoechoic pattern typical of autoimmune thyroiditis, but without antithyroid autoantibodies. Alterations of thyroid function in overweight and obese patients cause an increase in energy expenditure, which facilitates weight loss and prevents further weight gain. Therefore, normalisation of TSH and fT3 after weight loss could explain difficulties in maintaining reduced weight. (Endokrynol Pol 2017; 68 (1): 54–60) Obesity and thyroid function are closely related. Thyroid hormones are involved in the regulation of metabolism, thermogenesis, food intake, and fat oxidation. In obese children the most frequent hormonal abnormalities are slight hyperthyrotropinaemia and moderate increases in total T3 and/or fT3 concentrations. Those abnormalities are usually considered a cause of obesity, but according to recent studies, they should actually be considered an adaptation process aimed at increasing resting energy expenditure and total energy expenditure. Those abnormalities do not require any treatment and normalise after substantial weight loss. The mechanisms of those changes are dependent on leptin, thyroid hormone resistance, and mitochondrial dysfunction. The present paper describes the abovementioned mechanisms based on the latest research. We also present a review of some recent original studies evaluating thyroid function in overweight and obese children, including thyroid ultrasound. A thyroid ultrasound scan in obese children frequently shows increased thyroid volume, which correlates with moderately increased TSH levels and a hypoechoic pattern typical of autoimmune thyroiditis, but without antithyroid autoantibodies. Alterations of thyroid function in overweight and obese patients cause an increase in energy expenditure, which facilitates weight loss and prevents further weight gain. Therefore, normalisation of TSH and fT3 after weight loss could explain difficulties in maintaining reduced weight. (Endokrynol Pol 2017; 68 (1): 54–60)

The aim of the study was to investigate whether the Gln223Arg in the leptin receptor may influence body weight, leptin concentration, and metabolic parameters in children. The examined group included 101 obese children (58 girls and 43 boys) with BMI 31.41 ± 5.03 kg/m2 (BMI ≥ 2 SDS) and the control group consisted of 41 children with BMI 20.0 ± 0.80 kg/m2 (BMI < 1.0 SDS). Polymorphism identification was performed in total genomic DNA using PCRRFLP method. The distribution of genotypes LEPR was the following: in the obese group: AA - 20.8%, AG-55.4%, GG-23.8%; in the control group AA-31.7%, AG-53.65%, GG-14.65%. Comparative analyses between AA homozygous children and carriers of G alleles did not confirm any relation between the analyzed polymorphism and BMI, leptin concentrations, and metabolic disturbances in children with obesity. In children with obesity we did not observe association of the LEPR Gln223Arg gene polymorphism with obesity, leptin, insulin resistance, and metabolic abnormalities.