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The chemical chaperones tauroursodeoxycholic and 4‐phenylbutyric acid accelerate thyroid hormone activation and energy expenditure
Author(s) -
da-Silva Wagner S.,
Ribich Scott,
Drigo Rafael Arrojo e,
Castillo Melany,
Patti Mary-Elizabeth,
Bianco Antonio C.
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.12.044
Subject(s) - tauroursodeoxycholic acid , endocrinology , medicine , chemical chaperone , deiodinase , brown adipose tissue , iodothyronine deiodinase , chemistry , thyroid , hormone , adipose tissue , biology , unfolded protein response , biochemistry , thyroid hormones , endoplasmic reticulum
Exposure of cell lines endogenously expressing the thyroid hormone activating enzyme type 2 deiodinase (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 intolerance associated with high fat feeding. Thus, D2 plays a critical role in the metabolic effects of chemical chaperones.