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Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy
Rohit Anthony Sinha, … , Mitchell A. Lazar, Paul M. Yen
Rohit Anthony Sinha, … , Mitchell A. Lazar, Paul M. Yen
Published June 11, 2012
Citation Information: J Clin Invest. 2012;122(7):2428-2438. https://doi.org/10.1172/JCI60580.
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Research Article Metabolism Article has an altmetric score of 7

Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy

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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.

Authors

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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Figure 2

T3 stimulates autophagic flux and also induces autophagy in multiple hepatic cell lines.

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T3 stimulates autophagic flux and also induces autophagy in multiple hep...
(A–C) Immunoblot and densitometric for LC3-II showing autophagic flux using HepG2/TRα cells treated with 1 μM T3 and 50 μM CQ for 72 hours (n = 4; *P < 0.05). (D and E) Immunoblot analysis of LC3-II levels in AML-12, Hep3B, and Huh7 cells upon 1 μM T3 treatment for 72 hours showing increased autophagy (n = 3; *P < 0.05). Results are expressed as mean ± SEM.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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