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

Abstract

BackgroundImpaired 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.MethodsThe 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/m2) and 50 slim (BMI 20-24.9 kg/m2) individuals. The methylation status of these genes was studied by the methylation-sensitive digestion/real-time PCR method.ResultsThe 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.ConclusionsDecreased 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0395-2) contains supplementary material, which is available to authorized users.

17β-Estradiol suppresses visceral adipogenesis and activates brown adipose tissue-specific gene expression

“…The primers employed were designed using the web-based primer design tool Primer3. Primer pairs were designed to amplify the mouse homologues of regions which include CpG13S in the human SCD1 promoter [21], CpG48-50 in the human FASN promoter [21], methylation site #6 of the human CPT1b promoter [22] and regions amplified by the ADRB3 and DIO2 primers employed by Kurylowicz et al [23]. The specificity of amplification of each primer pair was verified by initial melting curve analyses.…”

Stimulation of Thermogenesis via Beta-Adrenergic and Thyroid Hormone Receptors Agonists in obesity Treatment – Possible Reasons for Therapy Resistance

“…Despite promising data from the in vitro and from animal studies, these agents occurred to have limited efficacy in humans, probably due to the (i) lower number of ADRB3 in human adipose tissue than in transfected cell-lines used for the in vitro experiments, (ii) poor selectivity of the compounds for the human ADRB3, and (iii) different contribution of white and brown adipocytes in rodents and in humans [49]. The lower expression of ADRB3 in adipose tissues of obese subjects may constitute another reason of low efficacy of these compounds in obesity treatment [50].…”

“…The isoforms have tissue-and organ specific localisation, with TRα1 being a predominant isoform in the brain, bone, heart and intestine, TRα2 -a variant receptor that lacks a functional hormone-binding site and antagonizes TRα1 action, TRβ1 dominating in liver, kidney and thyroid and TRβ2 being a chief form involved in the regulation of the hypothalamus-pituitary axis and in the neurosensory development [51]. Both TRα1 and TRβ1 are also expressed in human adipose tissue [50,52] and there is data coming from the observational, animal and genetic studies suggesting that they could constitute potential targets for obesity treatment.…”

“…There are also studies suggesting that thyroid status may influence not only general adiposity but also distribution of adipose tissue pointing at inverse correlation between the fT4 levels and visceral adiposity and at the positive correlation of TSH with the amount of subcutaneous fat [54]. This phenomenon can be partially explained by the differences in the TRs expression between the visceral and subcutaneous tissues as well as between obese and slim individuals [50]. The decreased expression of TRs in adipose tissues of obese individuals is also suggested as a potential mechanism of a relative resistance to thyroid hormone that manifests itself by the increased fT3 serum levels [52] and correlates positively with the increase in weight [55].…”

“…New TRα selective agonists are being studied in order to improve our understanding of the role of this isoform in termogenesis and other T3 regulated processes [74]. The effectiveness of these compounds, however, may be limited due to the decreased expression of THRA and THRB genes in adipose tissues of obese individuals [50,52].…”