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. 2015 Jan 27:13:31.
doi: 10.1186/s12967-015-0395-2.

Obesity is associated with a decrease in expression but not with the hypermethylation of thermogenesis-related genes in adipose tissues

Alina Kurylowicz  1 , Marta Jonas  2 , Wojciech Lisik  3 , Maurycy Jonas  4 , Zofia Agnieszka Wicik  5 , Zbigniew Wierzbicki  6 , Andrzej Chmura  7 , Monika Puzianowska-Kuznicka  8   9
Affiliations

Obesity is associated with a decrease in expression but not with the hypermethylation of thermogenesis-related genes in adipose tissues

Alina Kurylowicz et al. J Transl Med. .

Abstract

Background: Impaired thermogenesis can promote obesity. Therefore, the aim of this study was to investigate whether the expression of thermogenesis-related genes is altered in adipose tissues of obese individuals and whether excessive methylation of their promoters is involved in this phenomenon.

Methods: The expression of genes encoding β adrenergic receptors (ADRBs), thyroid hormone receptors (THRs), 5'-iodothyronine deiodinases (DIOs), and uncoupling proteins (UCPs) was measured by real-time PCR in visceral and in subcutaneous adipose tissues of 58 obese (BMI >40 kg/m(2)) and 50 slim (BMI 20-24.9 kg/m(2)) individuals. The methylation status of these genes was studied by the methylation-sensitive digestion/real-time PCR method.

Results: The expression of ADRB2, ADRB3, THRA, THRB, DIO2, UCP2 was significantly lower in the adipose tissues of obese patients than in tissues of normal-weight individuals (P < 0.00001). In the obese, the expression of ADRB2, ADRB3, DIO2 was lower in visceral adipose tissue than in subcutaneous adipose tissue (P = 0.008, P = 0.002, P = 0.001, respectively). However, the mean methylation of CpG islands of these genes was similar in tissues with their high and low expression, and there was no correlation between the level of expression and the level of methylation.

Conclusions: Decreased expression of thermogenesis-related genes in adipose tissues of obese patients might result in the reduced reactivity to both hormonal and adrenergic stimuli and therefore in a lower potential to activate thermogenesis.

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Figures

Figure 1
Figure 1
Comparison of the expression of ADRB1 (A), ADRB2 (B) and ADRB3 (C) genes in the visceral (VAT) and subcutaneous (SAT) adipose tissues of obese (O) and normal-weight (N) individuals. Results, normalized against the expression of ACTB, are shown as the mean ± standard deviation.
Figure 2
Figure 2
Comparison of the expression of DIO1 (A), DIO2 (B), THRA (C), and THRB (D) genes in the visceral (VAT) and subcutaneous (SAT) adipose tissues of obese (O) and normal-weight (N) individuals. Results, normalized against the expression of ACTB, are shown as the mean ± standard deviation.
Figure 3
Figure 3
Comparison of the expression of UCP1 (A), UCP2 (B), and of the UCP3 (C) genes in the visceral (VAT) and subcutaneous (SAT) adipose tissues of obese (O) and normal-weight (N) individuals. Results, normalized against the expression of ACTB, are shown as the mean ± standard deviation.
Figure 4
Figure 4
Correlation of the expression of ADRB2 (A), ADRB3 (B) , DIO2 (C), THRA (D) and THRB (E) with the methylation status of their promoters. Red dots represent samples with high whereas black – with low expression of the investigated gene.
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