Adipocyte Thyroid Hormone β Receptor-Mediated Hormone Action Fine-tunes Intracellular Glucose and Lipid Metabolism and Systemic Homeostasis

Thyroid hormone (TH) has a profound effect on energy metabolism and systemic homeostasis. Adipose tissues are crucial for maintaining whole-body homeostasis; however, whether TH regulates systemic metabolic homeostasis through its action on adipose tissues is unclear. Here, we demonstrate that systemic administration of triiodothyronine (T3), the active form of TH, affects both inguinal white adipose tissue (iWAT) and whole-body metabolism. Taking advantage of the mouse model lacking adipocyte TH receptor (TR) alpha or TR beta, we show that TR beta is the major TR isoform that mediates T3 action on the expression of genes involved in multiple metabolic pathways in iWAT, including glucose uptake and use, de novo fatty acid synthesis, and both UCP1-dependent and -independent thermogenesis. Moreover, our results indicate that glucose-responsive lipogenic transcription factor in iWAT is regulated by T3, thereby being critically involved in T3-regulated glucose and lipid metabolism and energy dissipation. Mice with adipocyte TR beta deficiency are susceptible to diet-induced obesity and metabolic dysregulation, suggesting that TR beta in adipocytes may be a potential target for metabolic diseases.

Automated summary

Thyroid hormone (TH) plays a crucial role in energy metabolism and systemic homeostasis by regulating adipose tissues. The active form of TH, triiodothyronine (T3), affects inguinal white adipose tissue (iWAT) and whole-body metabolism. Through the study of mice lacking adipocyte TH receptors (TR) alpha or TR beta, it was found that TR beta is the major mediator of T3's effects on iWAT, influencing metabolic pathways related to glucose uptake and use, fatty acid synthesis, and thermogenesis. Adipocyte TR beta deficiency in mice leads to susceptibility to diet-induced obesity and metabolic dysregulation, highlighting its potential as a target for metabolic diseases.