Visceral adipocyte metabolic dysfunction in obesity related to altered chromatin accessibility to thyroid hormone...

To explore the alterations in visceral adipose tissue (VAT) during obesity and identify the underlying mechanism causing the onset of VAT dysfunction.

Histological staining on human VAT was utilized. VAT samples were collected from individuals with normal weight (n = 3, BMI 21.77 ± 0.709) and obesity (n = 3, BMI 32.95 ± 1.815). RNA-seq and ATAC-seq were employed. In vitro cell experiment, Chromatin immunoprecipitation (CHIP) assay and RNA interference were conducted.

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 obesity, VAT metabolic function impairment is related to altered chromatin accessibility to thyroid hormone receptor. STAT5B is a key transcription factor at the core of the disrupted thyroid-adipose signaling and might be a promising target to improve obesity.