Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy

Rohit Anthony Sinha, Seo Hee You, Jin Zhou, Mobin M. Siddique, Boon Huat Bay, Xuguang Zhu, Martin L. Privalsky, Sheue Yann Cheng, Robert D. Stevens, Scott A. Summers, Christopher B. Newgard, Mitchell A. Lazar, Paul M. Yen

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126 Scopus citations

Abstract

For more than a century, thyroid hormones (THs) have been known to exert powerful catabolic effects, leading to weight loss. Although much has been learned about the molecular mechanisms used by TH receptors (TRs) to regulate gene expression, little is known about the mechanisms by which THs increase oxidative metabolism. Here, we report that TH stimulation of fatty acid β-oxidation is coupled with induction of hepatic autophagy to deliver fatty acids to mitochondria in cell culture and in vivo. Furthermore, blockade of autophagy by autophagy-related 5 (ATG5) siRNA markedly decreased TH-mediated fatty acid β-oxidation in cell culture and in vivo. Consistent with this model, autophagy was altered in livers of mice expressing a mutant TR that causes resistance to the actions of TH as well as in mice with mutant nuclear receptor corepressor (NCoR). These results demonstrate that THs can regulate lipid homeostasis via autophagy and help to explain how THs increase oxidative metabolism.

Original languageEnglish (US)
Pages (from-to)2428-2438
Number of pages11
JournalJournal of Clinical Investigation
Volume122
Issue number7
DOIs
StatePublished - Jul 2 2012

ASJC Scopus subject areas

  • Medicine(all)

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    Sinha, R. A., You, S. H., Zhou, J., Siddique, M. M., Bay, B. H., Zhu, X., Privalsky, M. L., Cheng, S. Y., Stevens, R. D., Summers, S. A., Newgard, C. B., Lazar, M. A., & Yen, P. M. (2012). Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy. Journal of Clinical Investigation, 122(7), 2428-2438. https://doi.org/10.1172/JCI60580