Thermogenic Gene Expression in Human Neck Adipose Tissue in Relation to Circulating and Local Thyroid Hormone Levels

Abstract Introduction Brown adipose tissue (BAT) contributes to thermogenesis and has been proposed as a therapeutic target for metabolic disease. Thyroid hormones (THs) regulate thermogenic activity, but the relationship between circulating and local TH concentrations and their associations with thermogenic gene and pathway expression in human adipose tissue remains unclear. Methods We obtained paired deep neck and subcutaneous (SC) adipose tissue samples from adults undergoing thyroid surgery, which represent BAT and white adipose tissue (WAT), respectively. Serum and local adipose tissue TH concentrations (T3, T4, TSH) were measured. Bulk RNA sequencing was performed on adipose tissue samples. Associations between hormone concentrations and thermogenic gene expression and pathway activation were analyzed, with false discovery rate (FDR) correction for multiple testing. Results Both serum and local T4 concentrations were positively associated with thermogenic pathway activation in deep neck adipose tissue. While serum T3 was also positively associated, local T3 was inversely associated with thermogenic pathways in deep neck adipose tissue. However, circulating TH concentrations did not correlate with local tissue hormone levels. No significant associations were observed between serum or local TH concentrations and individual thermogenic gene expression after correction for different clinical co-variates and multiple comparisons. Conclusion Local regulation of THs may play a role in human adipose tissue thermogenic activity. Pathway-level transcriptomic analysis may better capture these effects than single-gene approaches. Deep neck adipose tissue can serve as a practical model for studying BAT function and endocrine regulation in humans.