Thyroid Hormone Ameliorates Lymphedema by Suppressing Adipogenesis in a Murine Lymphedema Model

Background: Exogenous supplementation of thyroid hormone could inhibit excessive fat deposition in lymphedema tissue by suppressing adipogenesis. Methods and Results: Cell viability, adipogenic differentiation, and mRNA expression were measured in 3T3-L1 preadipocytes treated with L-thyroxine. Twelve mice were divided into control and L-thyroxine groups. Two weeks after lymphedema was surgically induced, the experimental mice were fed L-thyroxine for 4 weeks. Tail volume and body weight were measured, and 6 weeks after the surgery, tail skin and subcutaneous tissue were harvested for histopathologic examination and protein isolation. In 3T3-L1 cells, treatment with 10-500 μM L-thyroxine did not affect cell viability. Eight days after induction of adipogenic differentiation, lipid accumulation decreased significantly in the 50 and 100 μM L-thyroxine groups (p < 0.001). mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), and fatty acid-binding protein 4 (FABP4) decreased significantly in the 100 μM L-thyroxine group compared with the control group (p = 0.017). Lymphedema tails treated with L-thyroxine exhibited decreased volume (p = 0.028) and thickness of dermal and subcutaneous tissue (p = 0.01) and increased vascular endothelial growth factor-C protein expression (p = 0.017) compared with the control. Conclusion: Thyroid hormone therapy inhibits the adipogenesis of 3T3-L1 cells in vitro and decreases the volume of murine lymphedema tail in vivo. These findings suggest that thyroid hormone therapy could be used to treat lymphedema.