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Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy.

Publication ,  Journal Article
Sinha, RA; You, S-H; Zhou, J; Siddique, MM; Bay, B-H; Zhu, X; Privalsky, ML; Cheng, S-Y; Stevens, RD; Summers, SA; Newgard, CB; Lazar, MA; Yen, PM
Published in: J Clin Invest
July 2012

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.

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

July 2012

Volume

122

Issue

7

Start / End Page

2428 / 2438

Location

United States

Related Subject Headings

  • Triiodothyronine
  • Receptors, Thyroid Hormone
  • RNA Interference
  • Protein Binding
  • Phagosomes
  • Oxidation-Reduction
  • Oligonucleotide Array Sequence Analysis
  • Nuclear Receptor Co-Repressor 1
  • Microtubule-Associated Proteins
  • Mice, Inbred C57BL
 

Citation

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Sinha, R. A., You, S.-H., Zhou, J., Siddique, M. M., Bay, B.-H., Zhu, X., … Yen, P. M. (2012). Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy. J Clin Invest, 122(7), 2428–2438. https://doi.org/10.1172/JCI60580
Sinha, Rohit Anthony, Seo-Hee You, Jin Zhou, Mobin M. Siddique, Boon-Huat Bay, Xuguang Zhu, Martin L. Privalsky, et al. “Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy.J Clin Invest 122, no. 7 (July 2012): 2428–38. https://doi.org/10.1172/JCI60580.
Sinha RA, You S-H, Zhou J, Siddique MM, Bay B-H, Zhu X, et al. Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy. J Clin Invest. 2012 Jul;122(7):2428–38.
Sinha, Rohit Anthony, et al. “Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy.J Clin Invest, vol. 122, no. 7, July 2012, pp. 2428–38. Pubmed, doi:10.1172/JCI60580.
Sinha RA, You S-H, Zhou J, Siddique MM, Bay B-H, Zhu X, Privalsky ML, Cheng S-Y, Stevens RD, Summers SA, Newgard CB, Lazar MA, Yen PM. Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy. J Clin Invest. 2012 Jul;122(7):2428–2438.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

July 2012

Volume

122

Issue

7

Start / End Page

2428 / 2438

Location

United States

Related Subject Headings

  • Triiodothyronine
  • Receptors, Thyroid Hormone
  • RNA Interference
  • Protein Binding
  • Phagosomes
  • Oxidation-Reduction
  • Oligonucleotide Array Sequence Analysis
  • Nuclear Receptor Co-Repressor 1
  • Microtubule-Associated Proteins
  • Mice, Inbred C57BL