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) α or TRβ, we show that TRβ 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 TRβ deficiency are susceptible to diet-induced obesity and metabolic dysregulation, suggesting that TRβ in adipocytes may be a potential target for metabolic diseases.
Article highlights: How thyroid hormone (TH) achieves its diverse biological activities in the regulation of metabolism is not fully understood. Whether TH regulates systemic metabolic homeostasis via its action on white adipose tissue is unclear. Adipocyte TH receptor (TR) β mediates the triiodothyronine effect on multiple metabolic pathways by targeting glucose-responsive lipogenic transcription factor in white adipose tissue; mice lacking adipocyte TRβ are susceptible to high-fat diet-induced metabolic abnormalities. TRβ in white adipocytes controls intracellular and systemic metabolism and may be a potential target for metabolic diseases.
© 2023 by the American Diabetes Association.