Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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 Date

  • July 2012

Published In

Volume / Issue

  • 122 / 7

Start / End Page

  • 2428 - 2438

PubMed ID

  • 22684107

Pubmed Central ID

  • 22684107

Electronic International Standard Serial Number (EISSN)

  • 1558-8238

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI60580

Language

  • eng