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FEBS Lett. 2011 Feb 4;585(3):539-44. doi: 10.1016/j.febslet.2010.12.044. Epub 2011 Jan 14.

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

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1
Division of Endocrinology, Diabetes, and Metabolism, University of Miami Miller School of Medicine, Miami, FL 33143, USA.

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.

PMID:
21237159
PMCID:
PMC3133948
DOI:
10.1016/j.febslet.2010.12.044
[Indexed for MEDLINE]
Free PMC Article
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