ETA2022 Poster Presentations Thyroid Hormone ACTION (10 abstracts)
Deiodinase type I (DIO1) regulation in non-alcoholic fatty liver disease (NAFLD)
Nuria López Alcántara 1 , Cathleen Geissler 2 , Alison-Michelle Naujack 3 , Yingfu Chen 4 , Natalie Taege 3 , Jan H. Britsemmer 3 , Leonardo Vinicius Monteiro De Assis 5 , Henrik Oster 6 , Joachim Spranger 7 , Eva Katrin Wirth 8 , Ruben Nogueiras 9 , Henriette Kirchner 10 & Jens Mittag 11
1Universität zu Lübeck, Center of Brain, Behavior and Metabolism (Cbbm), Institute für Endokrinologie und Diabetes, Lübeck, Germany; 2Institute for Endocrinology and Diabetes, Center of Brain, Behavior and Metabolism (Cbbm), University of Lübeck, Germany, Nstitute for Human Genetics, Section Epigenetics & Metabolism, Center of Brain, Behavior and Metabolism (Cbbm), University of Lübeck, Germany, Institut für Humangenetik, Abteilung Epigenetik und Metabolismus, Lübeck, Germany; 3Universität zu Lübeck, Center of Brain, Behavior and Metabolism (Cbbm), Institut für Humangenetik, Abteilung Epigenetik und Metabolismus, Lübeck, Germany; 4Charité, Medizinsche Klinik für Endokrinologie, Berlin, Germany; 5Universität zu Lübeck, Center of Brain, Behavior and Metabolism (Cbbm), Institut für Neurobiologie, Lübeck, Germany; 6Medizinische Klinik I, Universität zu Lübeck, Institute of Neurobiology, University of Luebeck, Lübeck, Germany; 7Charité – Universitätsmedizin Berlin, Medizinische Klinik für Endokrinologie und Stoffwechselmedizin, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Endocrinology and Metabolism; 10117 Berlin, Germany, Endokrinologie, Berlin, Germany; 8Charité–universitätsmedizin Berlin, Dzhk (German Centre for Cardiovascular Research), Partner Site Berlin, Med. Klinik für Endokrinologie, Berlin, Germany; 9Cimus, University of Santiago de Compostela, Dept. of Physiology, Santiago de Compostela, Spain; 10Universität zu Lübeck, Medizinische Klinik I, Lübeck, Germany; 11Universität Lübeck, Cbbm / Medi, Cbbm, Molecular Endocrinology, Universität zu Lübeck, Lübeck, Germany, Lübeck, Germany
Background and Aim: Altered hepatic thyroid hormone (TH) signalling is associated with the onset and progression of liver diseases. Local hepatic hypothyroidism is related to a higher incidence of developing non-alcoholic fatty liver disease (NASH) in humans and animal models. Thyroid hormone treatment proved to be a promising therapy, slowing the progression of NAFLD to non-alcoholic steatohepatitis (NASH), a more advanced stage of the disease characterized by inflammation and occasional fibrosis. Hepatic thyroid hormone activity is regulated by TH transporters, deiodinases, and receptors. Among these, deiodinase type 1 (Dio1) is a major player, it converts the prohormone thyroxine (T4) to the bioactive form T3 within the hepatocytes. Unfortunately, the precise regulation of Dio1 in liver diseases remains incompletely understood.
Methods: We studied Dio1 expression in different hepatic disease models, including male C57BL/6 mice fed with high-fat diet (HFD) for 18 weeks and treated with metformin for the last four weeks of treatment, male C57BL/6 mice fed with choline-deficient HFD for 4 and 8 weeks at thermoneutrality, and finally, male C57BL/6 mice treated with carbon tetrachloride to induce liver failure.
Results: Dio1 expression is rapidly induced by HFD and remained elevated throughout the treatment without alterations by metformin treatment. Notably, none of the other conditions resulted in an induction of Dio1, despite a similar degree of liver lipid deposition.
Conclusion: Our results show that Dio1 is rapidly induced by HFD, an effect that seems to be independent of insulin sensitivity, as it was not reversed by metformin treatment. This effect was not visible in other animal models with a similar degree of hepatic lipid deposition, suggesting that other factors such as liver inflammation and fibrosis may prevent the HFD induced Dio1 induction. We suggest Dio1 increases as part of a protective response in NAFL and early NASH.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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