title: Differential effects of fasting vs food restriction on liver thyroid hormone metabolism in male rats.
abstract: A variety of illnesses that leads to profound changes in the hypothalamus-pituitary-thyroid (HPT) are axis collectively known as the nonthyroidal illness syndrome (NTIS). NTIS is characterized by decreased tri-iodothyronine (T3) and thyroxine (T4) and inappropriately low TSH serum concentrations, as well as altered hepatic thyroid hormone (TH) metabolism. Spontaneous caloric restriction often occurs during illness and may contribute to NTIS, but it is currently unknown to what extent. The role of diminished food intake is often studied using experimental fasting models, but partial food restriction might be a more physiologically relevant model. In this comparative study, we characterized hepatic TH metabolism in two models for caloric restriction: 36 h of complete fasting and 21 days of 50% food restriction. Both fasting and food restriction decreased serum T4 concentration, while after 36-h fasting serum T3 also decreased. Fasting decreased hepatic T3 but not T4 concentrations, while food restriction decreased both hepatic T3 and T4 concentrations. Fasting and food restriction both induced an upregulation of liver D3 expression and activity, D1 was not affected. A differential effect was seen in Mct10 mRNA expression, which was upregulated in the fasted rats but not in food-restricted rats. Other metabolic pathways of TH, such as sulfation and UDP-glucuronidation, were also differentially affected. The changes in hepatic TH concentrations were reflected by the expression of T3-responsive genes Fas and Spot14 only in the 36-h fasted rats. In conclusion, limited food intake induced marked changes in hepatic TH metabolism, which are likely to contribute to the changes observed during NTIS.
authors.affiliation: Department of Endocrinology and Metabolism Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands Hypothalamic Integration Mechanisms Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands Laboratory of Endocrinology Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands e.m.devries@amc.uva.nl.
authors.forename: E M
authors.initials: EM
authors.lastname: de Vries
authors.affiliation: Department of Endocrinology and Metabolism Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands Hypothalamic Integration Mechanisms Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands Laboratory of Endocrinology Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: H C
authors.initials: HC
authors.lastname: van Beeren
authors.affiliation: Department of Endocrinology and Metabolism Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands Hypothalamic Integration Mechanisms Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands Laboratory of Endocrinology Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: M T
authors.initials: MT
authors.lastname: Ackermans
authors.affiliation: Department of Endocrinology and Metabolism Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands Hypothalamic Integration Mechanisms Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands Laboratory of Endocrinology Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Department of Endocrinology and Metabolism Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands Hypothalamic Integration Mechanisms Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands Laboratory of Endocrinology Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Kalsbeek
authors.affiliation: Department of Endocrinology and Metabolism Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands Hypothalamic Integration Mechanisms Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands Laboratory of Endocrinology Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Fliers
authors.affiliation: Department of Endocrinology and Metabolism Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands Hypothalamic Integration Mechanisms Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands Laboratory of Endocrinology Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Boelen
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D031204:Caloric Restriction; D004435:Eating / Q000502:physiology; D005067:Euthyroid Sick Syndromes / Q000378:metabolism*; D005215:Fasting / Q000378:metabolism*; D005508:Food Deprivation; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013963:Thyroid Hormones / Q000097:blood / Q000378:metabolism*
chemical_list: D026921:Amino Acid Transport Systems, Neutral; C429535:Slc16a10 protein, rat; D013963:Thyroid Hormones; D007453:Iodide Peroxidase
keywords: liver; nutrition; rat; thyroid hormone metabolism