title: The chemical chaperones tauroursodeoxycholic and 4-phenylbutyric acid accelerate thyroid hormone activation and energy expenditure.
abstract: 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.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, University of Miami Miller School of Medicine, Miami, FL 33143, USA.
authors.forename: Wagner S
authors.initials: WS
authors.lastname: da-Silva
authors.forename: Scott
authors.initials: S
authors.lastname: Ribich
authors.forename: Rafael
authors.initials: R
authors.lastname: Arrojo e Drigo
authors.forename: Melany
authors.initials: M
authors.lastname: Castillo
authors.forename: Mary-Elizabeth
authors.initials: ME
authors.lastname: Patti
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Bianco
mesh_terms: D052437:Adipocytes, Brown / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004041:Dietary Fats / Q000009:adverse effects; D004734:Energy Metabolism / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D055786:Gene Knockout Techniques; D018149:Glucose Intolerance / Q000517:prevention & control; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010101:Oxygen Consumption / Q000187:drug effects; D010654:Phenylbutyrates / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*; D014284:Triiodothyronine / Q000378:metabolism*; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D004041:Dietary Fats; D007453:Iodide Peroxidase; D010654:Phenylbutyrates; D012333:RNA, Messenger; D013655:Taurochenodeoxycholic Acid; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II; C031655:ursodoxicoltaurine; C075773:4-phenylbutyric acid