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Publication : Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy.

First Author  Sinha RA Year  2012
Journal  J Clin Invest Volume  122
Issue  7 Pages  2428-38
PubMed ID  22684107 Mgi Jnum  J:190466
Mgi Id  MGI:5448895 Doi  10.1172/JCI60580
Citation  Sinha RA, et al. (2012) Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy. J Clin Invest 122(7):2428-38
abstractText  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 beta-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 beta-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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