Vital role of impaired thyroid- adipose signaling in functional alternation of visceral adipose tissue in the process of obesity

Obesity has become a nonnegligible problem over the world, leading to deleterious outcomes like metabolic syndrome, diabetes, and cardiovascular diseases, behind which, the dysfunction of visceral adipose tissue (VAT) played a crucial role in this process. To further understand the possible mechanisms behind this change, we carried out transcriptome sequencing (RNA seq) and assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) on VAT of lean and obese subjects. In the present study, RNA-seq revealed that 2478 genes were upregulated and 402 genes were downregulated in VAT from obese individuals. Through GO-p and KEGG analysis, we found that the downregulated genes were enriched in pathways concerning glucose metabolism, lipid metabolism and mitochondrial function, resembling the alternation occurred in hypothyroidism. Thyroid hormone, as the key regulator of energy metabolism, exerts vital effects on adipose tissue by altering these pathways, and through ATAC-seq, we found nine down-regulated genes involved in the target pathways with chromatin open region containing thyroid hormone receptor related binding sites. Thus, we speculated that the obesity related alternations in VAT may be associated with the defects of thyroid hormone signaling on these target genes, demonstrated as mitochondrial dysfunction, decreased fatty-acid beta oxidation, and impaired glucose utility, leading to obesity related complications.
RNA-seq and ATAC-seq results are partially uploaded, contact the correspond author for further information

肥胖问题在全球范围内已成为不可忽视的难题，其背后导致的代谢综合征、糖尿病及心血管疾病等有害后果不容忽视。在此过程中，内脏脂肪组织（VAT）的功能障碍扮演了至关重要的角色。为进一步探究这一变化背后的可能机制，我们对瘦型和肥胖个体的VAT进行了转录组测序（RNA-seq）及转座酶可及染色质的高通量测序（ATAC-seq）实验。在本研究中，RNA-seq结果显示，肥胖个体的VAT中上调基因2478个，下调基因402个。通过GO-p和KEGG分析，我们发现下调基因在涉及葡萄糖代谢、脂质代谢及线粒体功能的通路中富集，这与甲状腺功能减退症中发生的改变相似。甲状腺激素作为能量代谢的关键调节因子，通过改变这些通路对脂肪组织产生重要作用。通过ATAC-seq，我们发现了九个下调基因，这些基因参与的目标通路含有甲状腺激素受体相关结合位点的染色质开放区域。因此，我们推测肥胖相关的VAT变化可能与甲状腺激素信号在这些目标基因上的缺陷有关，这表现为线粒体功能障碍、脂肪酸β氧化减少和葡萄糖利用受损，进而导致肥胖相关并发症。
RNA-seq和ATAC-seq结果部分已上传，如需更多信息，请联系通讯作者。