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

Research output: Contribution to journalArticle

33 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)539-544
Number of pages6
JournalFEBS letters
Volume585
Issue number3
DOIs
StatePublished - Feb 4 2011

Keywords

  • Chemical chaperone
  • Deiodinase
  • Metabolism
  • Oxygen consumption
  • Thyroid hormone

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

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