ETA2022 Oral Presentations Oral Session 4: Basic 1 (5 abstracts)
Rewiring of liver diurnal transcriptome rhythms by triiodothyronine (T3) supplementation
Leonardo de Assis 1 , Lisbeth Harder 2 , Jose Thalles Lacerda 3 , Rex Parsons 4 , Meike Kaehler 5 , Ingolf Cascorbi 6 , Inga Nagel 7 , Oliver Rawashdeh 8 , Jens Mittag 9 & Henrik Oster 10
1Cbbm, Institute of Neurobiology, Lübeck, Germany; 2Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet,, Sweden; 3Institute of Bioscience, Department of Physiology, University of São Paulo, Brazil; 4Australian Centre for Health Services Innovation and Centre for Healthcare Transformation, School of Public Health and Social Work, Faculty of Health, Queensland University of Technology, Australia; 5Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Germany; 6Universitätsklinikum Schleswig-Holstein, Institut für Experimentelle und Klinische Pharmakologie, Institut für Experimentelle und Klinische Pharmakologie, Kiel, Germany; 7UKSH, Kiel, Germany; 8School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, Australia, Australia; 9Universität Lübeck, Cbbm / Medi, Cbbm, Molecular Endocrinology, Universität zu Lübeck, Lübeck, Germany, Lübeck, Germany; 10Medizinische Klinik I, Universität zu Lübeck, Institute of Neurobiology, University of Luebeck, Lübeck, Germany
Cellular 24-hour rhythms depend on transcriptional programs controlled by a set of circadian clock genes/proteins. Systemic factors like humoral and neuronal signals, oscillations in body temperature, and food intake align physiological circadian rhythms with external time. Thyroid hormones (THs) are major regulators of circadian clock target processes such as energy metabolism, but little is known about how fluctuations in TH levels affect the circadian coordination of tissue physiology. In this study, a high triiodothyronine (T3) state was induced in mice by supplementing T3 in the drinking water, which affected body temperature, and oxygen consumption in a time-of-day dependent manner. 24-hour transcriptome profiling of liver tissue identified 37 robustly and time independently T3 associated transcripts as potential TH state markers in the liver. Such genes participated in xenobiotic transport, lipid and xenobiotic metabolism. We also identified 10 – 15 % of the liver transcriptome as rhythmic in control and T3 groups, but only 4 % of the liver transcriptome (1,033 genes) were rhythmic across both conditions – amongst these several core clock genes. In-depth rhythm analyses showed that most changes in transcript rhythms were related to mesor (50%), followed by amplitude (10%), and phase (10%). Gene set enrichment analysis revealed TH state dependent reorganization of metabolic processes such as lipid and glucose metabolism. At high T3 levels, we observed weakening or loss of rhythmicity for transcripts associated with glucose and fatty acid metabolism, suggesting increased hepatic energy turnover. In sum, we provide evidence that tonic changes in T3 levels restructure the diurnal liver metabolic transcriptome independent of local molecular circadian clocks.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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