Work

Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy

Year: 2012

Type: article

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. Results TH (T 3 ) induces autophagy in TR-expressing HepG2 cells.To address the role of TH in hepatic autophagy in human liver, we studied the well-characterized HepG2 cell line, which retains many liver-spe-

Source: Journal of Clinical Investigation

DOI: 10.1172/jci60580