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Cited by 303Autophagy in Disease and TherapyThyroid Disorders and TreatmentsLipid metabolism and biosynthesis

Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy

Open access
Sinha, Rohit Anthony, You, Seo-Hee, Zhou, Jin, Siddique, Mobin M., Bay, Boon-Huat, Zhu, Xuguang, Privalsky, Martin L., Cheng, Sheue-Yann +5 more·2012·Journal of Clinical Investigation
DOI 10.1172/jci60580PMC PMC3386813
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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-

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  • Thyroid hormone activates autophagy in the liver and stimulates fatty acid β-oxidation and oxidative phosphorylation.

    “This could be critically important given that TH activates autophagy in the liver and stimulates fatty acid β-oxidation and oxidative phosphorylation (76).”

    From Emerging Therapies in Hypothyroidism (2024) · cites this paper as [76]

    The Abstract reports that thyroid hormone induces hepatic autophagy and stimulates fatty acid β-oxidation. A passage on T3-treated mouse livers reports more mitochondria, but says this only suggests an increase in oxidative phosphorylation; it does not establish that stimulation as a finding. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Authors
Sinha, R. A., You, S.-H., Zhou, J., Siddique, M. M., Bay, B.-H., Zhu, X., Privalsky, M. L., Cheng, S.-Y., Stevens, R. D., Summers, S. A., Newgard, C. B., Lazar, M. A., & Yen, P. M.
Affiliations
  • Duke-NUS Medical School (SG)
  • University of Pennsylvania (US)
  • National University of Singapore (SG)
  • National Institutes of Health (US)
  • National Cancer Institute (US)
  • Duke University (US)
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2012-07-02
Volume
122
Issue
7
Pages
2428-2438
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci60580
PMC
PMC3386813
OpenAlex
W2162155294
Cited by
303
References
5
Citations by year
2026: 12 · 2025: 41 · 2024: 31 · 2023: 21 · 2022: 26 · 2021: 26 · 2020: 15 · 2019: 23 · 2018: 19 · 2017: 20 · 2016: 21 · 2015: 13 · 2014: 15 · 2013: 17 · 2012: 3
FWCI
11.49
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • National University of Singapore (submittedVersion)
Funders
  • American Diabetes Association
  • University of Pennsylvania
  • Duke-NUS Medical School
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK43806, U19DK/HL/ES 62434, R37DK043806, R01DK043806)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
thyroid hormones, hepatic autophagy, fatty acid beta-oxidation, lipid degradation, thyroid hormone receptor, ATG5, nuclear receptor corepressor, oxidative metabolism, hepatic lipid homeostasis, weight loss
MeSH terms
Autophagy-Related Protein 5, Histone Deacetylase 3, Animals, Autophagy, Carnitine, Fatty Acids, Histone Deacetylases, Humans, Ketone Bodies, Liver, Male, Mice, Inbred C57BL, Microtubule-Associated Proteins, Oxidation-Reduction, Phagosomes, Protein Binding, Receptors, Thyroid Hormone, Triiodothyronine, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Hepatocytes, RNA Interference, Cell Line, Tumor, Lipid Metabolism, Mice, Metabolic Networks and Pathways, Metabolome, Gene Knockdown Techniques, Nuclear Receptor Co-Repressor 1

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