Introduction: Thermogenesis constitutes an important part of energy expenditure and its disturbances may contribute to the development of obesity. The aim of this study was to investigate whether the expression of thermogenesis-related genes differs in adipose tissues of obese and normal-weight individuals and if methylation of CpG islands located in the regulatory regions of these genes is involved in this phenomenon.
Materials and methods: The expression of genes encoding β adrenergic receptors (ADRB1, ADRB2, ADRB3), thyroid hormone receptors α (THRA) and β (THRB), 5-iodothyronine deiodinases type 1 and 2 (DIO1, DIO2), and of uncoupling proteins (UCP1, UCP2, UCP3) was analyzed by RT-PCR in visceral (VAT) and in subcutaneous (SAT) adipose tissues of patients with BMI>40 kg/m2 and patients with BMI=20-24.9 kg/m2. Methylation of the regulatory regions of these genes was studied by real-time PCR preceded by digestion with the methylation-sensitive endonucleases.
Results: The mRNA levels of ADRB2, ADRB3, THRA, THRB, DIO2, and UCP2 were significantly lower in adipose tissues of obese than of normal-weight individuals (P<0.00001, P<0.00001, P=0.0002, P=0.0001, P=0.0003, P=0.002 respectively). Obesity was also associated with a lower expression of ADRB2, ADRB3 and DIO2 in VAT than in SAT (P=0.008, P=0.0002, P=0.001 respectively). The mean methylation of ADRB2, ADRB3, THRA, THRB, and DIO2 in tissues with high and with low expression of a given gene did not differ significantly. In addition, there was no correlation between the level of expression and the degree of methylation.
Conclusions: We observed the decreased expression of thermogenesis-related genes in adipose tissues of obese patients. This phenomenon may result in a lower reactivity of their adipocytes to hormonal and to adrenergic stimuli and in lower potential to activate thermogenesis in response to novel therapeutic compounds targeting proteins encoded by these genes. The regulatory mechanisms involved in this phenomenon remain unknown.