Visceral adipocyte metabolic dysfunction in obesity related to altered chromatin accessibility to thyroid hormone receptor [ATAC-seq]

Adipocyte dysfunctuon exacerbates obesity, yet the onset of adipocyte dysfunction is still unclear. Here, we employed RNA-seq and ATAC-seq on visceral adipose tissue from individuals with obesity or normal weight.Our research identified differentially expressed genes (DEGs) of VAT from individuals with normal wight or obesity enriched in pathways related to adipocyte metabolic function, thyroid hormone receptor binding sites were discovered in the accessible chromatin regions of these DEGs, including STAT5B. Motif enrichment, CHIP assay and in vitro cell experiments confirmed the decreased activation of STAT5B by triiodothyronine (T3) through binding with thyroid hormone receptor alpha (THRa) in obesity. In addition, RNA interference revealed STAT5B as a key transcription factor in maintaining the metabolic function of VAT. In conclusion, the impaired metabolic function of VAT is associated with altered chromatin accessibility to thyroid hormone (TH) in obesity. STAT5B is a key transcription factor at the core of the disrupted thyroid-adipose signaling and might be a promising target to improve obesity. RNA-seq and ATAC-seq on visceral adipose tissue from 3 human individuals with normal weight and 3 human inviduals with obesity.