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