ArticlePloS one2015
The amelioration of hepatic steatosis by thyroid hormone receptor agonists is insufficient to restore insulin sensitivity in ob/ob mice.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Thyroid hormone acts independently of the thyroid hormone receptor beta in hepatocytes to improve systemic insulin sensitivity.Hepatology communications · 2026Article
- Nuclear Receptor-Targeted Therapies: Reprogramming Metabolism with TRβ, ERRα, and LXR Modulators.Biomolecules · 2026Review
- Lipid Hormones at the Intersection of Metabolic Imbalances and Endocrine Disorders.Current issues in molecular biology · 2025Review
- Drug Pipeline for MASLD: What Can Be Learned from the Successful Story of Resmetirom.Current issues in molecular biology · 2025Review
- Drug discovery targeting thyroid hormone receptorActa pharmaceutica Sinica. B · 2025Review
- Metabolic Messengers: Thyroid Hormones.Nature metabolism · 2024Review
- Effects of Thyroid Hormones on Lipid Metabolism Pathologies in Non-Alcoholic Fatty Liver Disease.Biomedicines · 2022Review
- Development of Thyroid Hormones and Synthetic Thyromimetics in Non-Alcoholic Fatty Liver Disease.International journal of molecular sciences · 2022Review
- Inflammatory and fibrotic mechanisms in NAFLD-Implications for new treatment strategies.Journal of internal medicine · 2022Review
- [New development for targeted therapy of non-alcoholic fatty liver disease with thyroid hormone receptor beta].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2021Article
- Thyroid hormones in diabetes, cancer, and aging.Aging cell · 2020Review
- Thyroid Hormone Analogues: An Update.Thyroid : official journal of the American Thyroid Association · 2020Review
- Nonalcoholic Fatty Liver Disease and Hypercholesterolemia: Roles of Thyroid Hormones, Metabolites, and Agonists.Thyroid : official journal of the American Thyroid Association · 2019Review
- Molecular functions and clinical impact of thyroid hormone-triggered autophagy in liver-related diseases.Journal of biomedical science · 2019Review
- Nonalcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases.Cell metabolism · 2018Review
- Thyroid Hormones, Thyromimetics and Their Metabolites in the Treatment of Liver Disease.Frontiers in endocrinology · 2018Review
- GC-1: A Thyromimetic With Multiple Therapeutic Applications in Liver Disease.Gene expression · 2017Review
- Regulation of hepatic glucose metabolism in health and disease.Nature reviews. Endocrinology · 2017Review
- Nonalcoholic fatty liver disease: Evolving paradigms.World journal of gastroenterology · 2017Review
- Endocrine-disrupting chemicals and fatty liver disease.Nature reviews. Endocrinology · 2017Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
Thyroid hormone receptor (TR) agonists have been proposed as therapeutic agents to treat non-alcoholic fatty liver disease (NAFLD) and insulin resistance. We investigated the ability of the TR agonists GC-1 and KB2115 to reduce hepatic steatosis in ob/ob mice. Both compounds markedly reduced hepatic triglyceride levels and ameliorated hepatic steatosis. However, the amelioration of fatty liver was not sufficient to improve insulin sensitivity in these mice and reductions in hepatic triglycerides did not correlate with improvements in insulin sensitivity or glycemic control. Instead, the effects of TR activation on glycemia varied widely and were found to depend upon the time of treatment as well as the compound and dosage used. Lower doses of GC-1 were found to further impair glycemic control, while a higher dose of the same compound resulted in substantially improved glucose tolerance and insulin sensitivity, despite all doses being equally effective at reducing hepatic triglyceride levels. Improvements in glycemic control and insulin sensitivity were observed only in treatments that also increased body temperature, suggesting that the induction of thermogenesis may play a role in mediating these beneficial effects. These data illustrate that the relationship between TR activation and insulin sensitivity is complex and suggests that although TR agonists may have value in treating NAFLD, their effect on insulin sensitivity must also be considered.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.