Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy

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

Research output: Contribution to journalArticle

112 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2428-2438
Number of pages11
JournalJournal of Clinical Investigation
Volume122
Issue number7
DOIs
StatePublished - Jul 2 2012

Fingerprint

Autophagy
Thyroid Hormones
Lipids
Liver
Fatty Acids
Cell Culture Techniques
Thyroid Hormone Receptors
Co-Repressor Proteins
Small Interfering RNA
Weight Loss
Mitochondria
Homeostasis
Gene Expression

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Sinha, R. A., You, S. H., Zhou, J., Siddique, M. M., Bay, B. H., Zhu, X., ... Yen, P. M. (2012). Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy. Journal of Clinical Investigation, 122(7), 2428-2438. https://doi.org/10.1172/JCI60580

Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy. / Sinha, Rohit Anthony; You, Seo Hee; Zhou, Jin; Siddique, Mobin M.; Bay, Boon Huat; Zhu, Xuguang; Privalsky, Martin L.; Cheng, Sheue Yann; Stevens, Robert D.; Summers, Scott A.; Newgard, Christopher B.; Lazar, Mitchell A.; Yen, Paul M.

In: Journal of Clinical Investigation, Vol. 122, No. 7, 02.07.2012, p. 2428-2438.

Research output: Contribution to journalArticle

Sinha, RA, You, SH, Zhou, J, Siddique, MM, Bay, BH, Zhu, X, Privalsky, ML, Cheng, SY, Stevens, RD, Summers, SA, Newgard, CB, Lazar, MA & Yen, PM 2012, 'Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy', Journal of Clinical Investigation, vol. 122, no. 7, pp. 2428-2438. https://doi.org/10.1172/JCI60580
Sinha, Rohit Anthony ; You, Seo Hee ; Zhou, Jin ; Siddique, Mobin M. ; Bay, Boon Huat ; Zhu, Xuguang ; Privalsky, Martin L. ; Cheng, Sheue Yann ; Stevens, Robert D. ; Summers, Scott A. ; Newgard, Christopher B. ; Lazar, Mitchell A. ; Yen, Paul M. / Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy. In: Journal of Clinical Investigation. 2012 ; Vol. 122, No. 7. pp. 2428-2438.
@article{043cb18315d446c8adc9412105e54c58,
title = "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.",
author = "Sinha, {Rohit Anthony} and You, {Seo Hee} and Jin Zhou and Siddique, {Mobin M.} and Bay, {Boon Huat} and Xuguang Zhu and Privalsky, {Martin L.} and Cheng, {Sheue Yann} and Stevens, {Robert D.} and Summers, {Scott A.} and Newgard, {Christopher B.} and Lazar, {Mitchell A.} and Yen, {Paul M.}",
year = "2012",
month = "7",
day = "2",
doi = "10.1172/JCI60580",
language = "English (US)",
volume = "122",
pages = "2428--2438",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "7",

}

TY - JOUR

T1 - Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy

AU - Sinha, Rohit Anthony

AU - You, Seo Hee

AU - Zhou, Jin

AU - Siddique, Mobin M.

AU - Bay, Boon Huat

AU - Zhu, Xuguang

AU - Privalsky, Martin L.

AU - Cheng, Sheue Yann

AU - Stevens, Robert D.

AU - Summers, Scott A.

AU - Newgard, Christopher B.

AU - Lazar, Mitchell A.

AU - Yen, Paul M.

PY - 2012/7/2

Y1 - 2012/7/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84863544286&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863544286&partnerID=8YFLogxK

U2 - 10.1172/JCI60580

DO - 10.1172/JCI60580

M3 - Article

VL - 122

SP - 2428

EP - 2438

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 7

ER -