Exposure of cell lines endogenously expressing the thyroid hormone activating enzyme type 2 deio- dinase (D2) to the chemical chaperones tauroursodeoxycholic acid (TUDCA) or 4-phenylbutiric acid (4-PBA) increases D2 expression, activity and T3 production. In brown adipocytes, TUDCA or 4-PBA induced T3-dependent genes and oxygen consumption ( 2-fold), an effect partially lost in D2 knockout cells. In wild type, but not in D2 knockout mice, administration of TUDCA lowered the respiratory quotient, doubled brown adipose tissue D2 activity and normalized the glucose intoler- ance associated with high fat feeding. Thus, D2 plays a critical role in the metabolic effects of chem- ical chaperones.
The chemical chaperones tauroursodeoxycholic and 4-phenylbutyric acid accelerate thyroid hormone activation and energy expenditure.
Wagner S. da-Silva, Scott Ribich, Rafael Arrojo e Drigo, Melany Castillo, Mary-Elizabeth Patti, Antonio C. Bianco. Federation of European Biochemical Societies. 14 January, 2011; doi:10.1016/j.febslet.2010.12.044