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.
View: Text | PDF
Research Article Metabolism

Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy

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

×
Problems with a PDF?

This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.

Having trouble reading a PDF?

PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.

Having trouble saving a PDF?

Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.

Having trouble printing a PDF?

  1. Try printing one page at a time or to a newer printer.
  2. Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
  3. Make sure you are using the latest version of Adobe's Acrobat Reader.

Supplemental data - Download (2.08 MB)

Advertisement