The effect of diet-induced weight-loss on subcutaneous adipose tissue expression of genes associated with thyroid hormone action

Background & aims

We have recently demonstrated that subcutaneous adipose tissue (SAT) expression of genes associated with thyroid hormone (TH) action is altered in obesity and insulin resistance. The aim of the present study was to examine the effect of diet-induced weight-loss on SAT expression of genes associated with TH action.

Methods

The study group comprised 38 individuals with overweight/obesity, which completed 12-week dietary intervention program. Hyperinsulinemic-euglycemic clamp and SAT biopsy were performed before and after the program. Fifteen normal-weight individuals were examined at baseline only.

Results

Overweight/obese individuals had lower free thyroxine (fT4) and higher free triiodothyronine (fT3)/fT4 ratio, lower SAT TH receptor isoforms (TRα and TRβ, encoded by THRA and THRB, respectively) and peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A) mRNA expression and higher SAT type II and type III iodothyronine deiodinase (encoded by DIO2 and DIO3, respectively) and nuclear receptor corepressor (NCOR1) mRNA expression in comparison with normal-weight individuals. Diet-induced weight loss resulted in a decrease in fT3 and fT3/fT4 ratio and an increase in SAT THRA, THRB and PPARGC1A. SAT NCOR1 and forkhead box protein O1 (FOXO1) decreased only in individuals, who lost at least 10 kg (n = 20). Higher increase in insulin sensitivity after weight loss was associated with a lower decrease in fT3/fT4 ratio.

Conclusions

Diet-induced weight loss partly reverses alterations in SAT expression of genes associated with TH action. Responses of circulating TH and SAT expression of genes associated with TH action to diet-induced weight loss are related to body weight and insulin sensitivity.