Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Student Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.
BMC Endocr Disord. 2023 Jan 6;23(1):7. doi: 10.1186/s12902-022-01247-5.
Animal model studies suggest that change in the members of the suppressor of the cytokine signaling (SOCS) family (mainly SOCS1 and SOCS3) is linked to the pathogenesis of obesity-related metabolic disorders. Moreover, epigenetic modification is involved in the transcriptional regulation of the SOCS gene family. Here, we aimed to evaluate the mRNA expression as well as gene promoter methylation of SOCS1 and SOCS3 in subcutaneous adipose tissue (SAT) from obese women compared to normal-weight subjects. We also intend to identify the possible association of SOCS1 and SOCS3 transcript levels with metabolic parameters in the context of obesity.
This study was conducted on women with obesity (n = 24) [body mass index (BMI) ≥ 30 kg/m ] and women with normal-weight (n = 22) (BMI < 25 kg/m ). Transcript levels of SOCS1 and SOCS3 were evaluated by real-time PCR in SAT from all participants. After bisulfite treatment of DNA, methylation-specific PCR was used to assess the putative methylation of 10 CpG sites in the promoter of SOCS1 and 13 CpG sites in SOCS3 in SAT from women with obesity and normal weight.
It was found that unlike SOCS3, which disclosed an elevating expression pattern, the expression level of SOCS1 was lower in the women with obesity as compared with their non-obese counterparts (P-value = 0.03 for SOCS1 transcript level and P-value = 0.011 for SOCS3 transcript level). As for the analysis of promoter methylation, it was found that SOCS1 and SOCS3 methylation were not significantly different between the individuals with obesity and normal weight (P-value = 0.45 and P-value = 0.89). Correlation analysis indicated that the transcript level of SOCS1 mRNA expression had an inverse correlation with BMI, hs-CRP levels, HOMA-IR, and insulin levels. However, the SOCS3 transcript level showed a positive correlation with BMI, waist-to-height ratio, waist circumference, hip circumference, hs-CRP, HOMA-IR, insulin, fasting blood glucose, and total cholesterol. Interestingly, HOMA-IR is the predictor of the transcript level of SOCS1 (β = - 0.448, P-value = 0.003) and SOCS3 (β = 0.465, P-value = 0.002) in SAT of all participants.
Our findings point to alterations of SOCS1 and SOCS3 transcript levels, but not promoter methylation levels in subcutaneous adipose tissues from women with obesity. Moreover, mRNA expression of SOCS1 and SOCS3 in SAT was associated with known obesity indices, insulin resistance, and hs-CRP, suggesting the contribution of SOCS1 and SOCS3 in the pathogenesis of obesity-related metabolic abnormalities. However, further studies are required to establish this concept.
动物模型研究表明，细胞因子信号转导抑制因子（SOCS）家族成员（主要为 SOCS1 和 SOCS3）的变化与肥胖相关代谢紊乱的发病机制有关。此外，表观遗传修饰参与 SOCS 基因家族的转录调控。在此，我们旨在评估肥胖女性与正常体重女性的皮下脂肪组织（SAT）中 SOCS1 和 SOCS3 的 mRNA 表达以及基因启动子甲基化。我们还旨在确定 SOCS1 和 SOCS3 转录水平与肥胖相关代谢参数的可能关联。
本研究纳入肥胖女性（n=24）[体重指数（BMI）≥30 kg/m ]和正常体重女性（n=22）（BMI<25 kg/m ）。使用实时 PCR 评估所有参与者 SAT 中 SOCS1 和 SOCS3 的转录水平。对 DNA 进行亚硫酸氢盐处理后，使用甲基化特异性 PCR 评估肥胖和正常体重女性 SAT 中 SOCS1 启动子的 10 个 CpG 位点和 SOCS3 启动子的 13 个 CpG 位点的假定甲基化。
与 SOCS3 的表达水平升高不同，SOCS1 的表达水平在肥胖女性中低于非肥胖女性（SOCS1 转录水平的 P 值=0.03，SOCS3 转录水平的 P 值=0.011）。至于启动子甲基化分析，发现肥胖和正常体重个体之间 SOCS1 和 SOCS3 的甲基化没有显著差异（P 值=0.45 和 P 值=0.89）。相关性分析表明，SOCS1 mRNA 表达的转录水平与 BMI、hs-CRP 水平、HOMA-IR 和胰岛素水平呈负相关。然而，SOCS3 转录水平与 BMI、腰高比、腰围、臀围、hs-CRP、HOMA-IR、胰岛素、空腹血糖和总胆固醇呈正相关。有趣的是，HOMA-IR 是所有参与者 SAT 中 SOCS1（β=-0.448，P 值=0.003）和 SOCS3（β=0.465，P 值=0.002）转录水平的预测因子。
我们的发现表明，肥胖女性的皮下脂肪组织中 SOCS1 和 SOCS3 的转录水平发生了变化，但启动子甲基化水平没有变化。此外，SAT 中 SOCS1 和 SOCS3 的 mRNA 表达与已知的肥胖指数、胰岛素抵抗和 hs-CRP 相关，提示 SOCS1 和 SOCS3 参与了肥胖相关代谢异常的发病机制。然而，需要进一步的研究来确定这一概念。
