The chemical chaperones tauroursodeoxycholic and 4-phenylbutyric acid accelerate thyroid hormone activation and energy expenditure.

da-Silva WS, Ribich S, Arrojo e Drigo R, Castillo M, Patti ME, Bianco AC
FEBS Lett. 2011 585 (3): 539-44

PMID: 21237159 · PMCID: PMC3133948 · DOI:10.1016/j.febslet.2010.12.044

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.

Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

MeSH Terms (21)

Adipocytes, Brown Animals Cell Line Cells, Cultured Dietary Fats Energy Metabolism Gene Expression Regulation Gene Knockout Techniques Glucose Intolerance Humans Iodide Peroxidase Lipid Metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Oxygen Consumption Phenylbutyrates RNA, Messenger Taurochenodeoxycholic Acid Triiodothyronine

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