ArticleProceedings of the National Academy of Sciences of the United States of America2015
Perinatal deiodinase 2 expression in hepatocytes defines epigenetic susceptibility to liver steatosis and obesity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 43 citations in OpenAlex.
- Construction of liver organoid models by hepatobiliary differentiation from human induced pluripotent stem cells: state of the art, challenges and improving strategies.Stem cell research & therapy · 2026Review
- Thyroid hormones and metabolic flexibility: tissue-specific control of energy homeostasis.Frontiers in physiology · 2026Review
- Selenium and selenoproteins in age-related metabolic diseases: mechanistic insights and translational perspectives.Frontiers in nutrition · 2026Review
- Detection of a large antigen through the masking and exposure of a fragment of split luciferase.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2025Article
- Actions of thyroid hormones and thyromimetics on the liver.Nature reviews. Gastroenterology & hepatology · 2025Review
- Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application.Signal transduction and targeted therapy · 2024Review
- Thyroid Hormone Biomonitoring: A Review on Their Metabolism and Machine-Learning Based Analysis on Effects of Endocrine Disrupting Chemicals.Environment & health (Washington, D.C.) · 2024Review
- Genetic Background Strongly Influences the Impact of Carrying the Thr92Ala-DIO2 Polymorphism in the Male Mouse.Endocrinology · 2024Article
- Localized T3 production modifies the transcriptome and promotes the hepatocyte-like lineage in iPSC-derived hepatic organoids.JCI insight · 2023Article
- Polymorphisms within DIO2 and GADD45A genes increase the risk of liver disease progression in chronic hepatitis b carriers.Scientific reports · 2023Article
- Thyroid hormone as a temporal switch in mouse development.European thyroid journal · 2023Review
- Hepatic Energy Metabolism under the Local Control of the Thyroid Hormone System.International journal of molecular sciences · 2023Review
- Epigenetic developmental programming and intergenerational effects of thyroid hormones.Vitamins and hormones · 2023Review
- Inactivation of Type 3 Deiodinase Results in Life-long Changes in the Brown Adipose Tissue Transcriptome in the Male Mouse.Endocrinology · 2022Article
- Too Much Too Soon-Tissue-specific Inactivation of Deiodinase Type 3 Prematurely Exposes Brown Fat to Thyroid Hormone.Endocrinology · 2022Article
- Deiodinases and the Three Types of Thyroid Hormone Deiodination Reactions.Endocrinology and metabolism (Seoul, Korea) · 2021Review
- Thyroid Hormone Deiodinases: Dynamic Switches in Developmental Transitions.Endocrinology · 2021Review
- Deiodinases and the Metabolic Code for Thyroid Hormone Action.Endocrinology · 2021Review
- Neonatal thyroxine activation modifies epigenetic programming of the liver.Nature communications · 2021Article
- Iodine Deficiency Increases Fat Contribution to Energy Expenditure in Male Mice.Endocrinology · 2020Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
Thyroid hormone binds to nuclear receptors and regulates gene transcription. Here we report that in mice, at around the first day of life, there is a transient surge in hepatocyte type 2 deiodinase (D2) that activates the prohormone thyroxine to the active hormone triiodothyronine, modifying the expression of ∼165 genes involved in broad aspects of hepatocyte function, including lipid metabolism. Hepatocyte-specific D2 inactivation (ALB-D2KO) is followed by a delay in neonatal expression of key lipid-related genes and a persistent reduction in peroxisome proliferator-activated receptor-γ expression. Notably, the absence of a neonatal D2 peak significantly modifies the baseline and long-term hepatic transcriptional response to a high-fat diet (HFD). Overall, changes in the expression of approximately 400 genes represent the HFD response in control animals toward the synthesis of fatty acids and triglycerides, whereas in ALB-D2KO animals, the response is limited to a very different set of only approximately 200 genes associated with reverse cholesterol transport and lipase activity. A whole genome methylation profile coupled to multiple analytical platforms indicate that 10-20% of these differences can be related to the presence of differentially methylated local regions mapped to sites of active/suppressed chromatin, thus qualifying as epigenetic modifications occurring as a result of neonatal D2 inactivation. The resulting phenotype of the adult ALB-D2KO mouse is dramatic, with greatly reduced susceptibility to diet-induced steatosis, hypertriglyceridemia, and obesity.
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