Orally Induced Hyperthyroidism Regulates Hypothalamic AMP-Activated Protein Kinase
Besides their direct effects on peripheral metabolic tissues, thyroid hormones (TH) act on the hypothalamus to modulate energy homeostasis. However, since most of the hypothalamic actions of TH have been addressed in studies with direct central administration, the estimation of the relative contribu...
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MDPI AG
2021-11-01
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| author | Valentina Capelli Carmen Grijota-Martínez Nathalia R. V. Dragano Eval Rial-Pensado Johan Fernø Rubén Nogueiras Jens Mittag Carlos Diéguez Miguel López |
| author_facet | Valentina Capelli Carmen Grijota-Martínez Nathalia R. V. Dragano Eval Rial-Pensado Johan Fernø Rubén Nogueiras Jens Mittag Carlos Diéguez Miguel López |
| author_sort | Valentina Capelli |
| collection | DOAJ |
| description | Besides their direct effects on peripheral metabolic tissues, thyroid hormones (TH) act on the hypothalamus to modulate energy homeostasis. However, since most of the hypothalamic actions of TH have been addressed in studies with direct central administration, the estimation of the relative contribution of the central vs. peripheral effects in physiologic conditions of peripheral release (or administration) of TH remains unclear. In this study we used two different models of peripherally induced hyperthyroidism (i.e., T4 and T3 oral administration) to assess and compare the serum and hypothalamic TH status and relate them to the metabolic effects of the treatment. Peripheral TH treatment affected feeding behavior, overall growth, core body temperature, body composition, brown adipose tissue (BAT) morphology and uncoupling protein 1 (UCP1) levels and metabolic activity, white adipose tissue (WAT) browning and liver metabolism. This resulted in an increased overall uncoupling capacity and a shift of the lipid metabolism from WAT accumulation to BAT fueling. Both peripheral treatment protocols induced significant changes in TH concentrations within the hypothalamus, with T3 eliciting a downregulation of hypothalamic AMP-activated protein kinase (AMPK), supporting the existence of a central action of peripheral TH. Altogether, these data suggest that peripherally administered TH modulate energy balance by various mechanisms; they also provide a unifying vision of the centrally mediated and the direct local metabolic effect of TH in the context of hyperthyroidism. |
| first_indexed | 2024-03-10T03:25:52Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T03:25:52Z |
| publishDate | 2021-11-01 |
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| series | Nutrients |
| spelling | doaj.art-ebc1e718f1224c7393b42b40cf6fe6032023-11-23T09:54:26ZengMDPI AGNutrients2072-66432021-11-011312420410.3390/nu13124204Orally Induced Hyperthyroidism Regulates Hypothalamic AMP-Activated Protein KinaseValentina Capelli0Carmen Grijota-Martínez1Nathalia R. V. Dragano2Eval Rial-Pensado3Johan Fernø4Rubén Nogueiras5Jens Mittag6Carlos Diéguez7Miguel López8Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, 15782 Santiago de Compostela, SpainDepartment of Cell Biology, Faculty of Biology, Complutense University, 28040 Madrid, SpainDepartment of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, 15782 Santiago de Compostela, SpainDepartment of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, 15782 Santiago de Compostela, SpainHormone Laboratory, Haukeland University Hospital, N-5021 Bergen, NorwayDepartment of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, 15782 Santiago de Compostela, SpainInstitute for Endocrinology and Diabetes—Molecular Endocrinology, Center of Brain Behavior and Metabolism CBBM, University of Lübeck, 23562 Lübeck, GermanyDepartment of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, 15782 Santiago de Compostela, SpainDepartment of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, 15782 Santiago de Compostela, SpainBesides their direct effects on peripheral metabolic tissues, thyroid hormones (TH) act on the hypothalamus to modulate energy homeostasis. However, since most of the hypothalamic actions of TH have been addressed in studies with direct central administration, the estimation of the relative contribution of the central vs. peripheral effects in physiologic conditions of peripheral release (or administration) of TH remains unclear. In this study we used two different models of peripherally induced hyperthyroidism (i.e., T4 and T3 oral administration) to assess and compare the serum and hypothalamic TH status and relate them to the metabolic effects of the treatment. Peripheral TH treatment affected feeding behavior, overall growth, core body temperature, body composition, brown adipose tissue (BAT) morphology and uncoupling protein 1 (UCP1) levels and metabolic activity, white adipose tissue (WAT) browning and liver metabolism. This resulted in an increased overall uncoupling capacity and a shift of the lipid metabolism from WAT accumulation to BAT fueling. Both peripheral treatment protocols induced significant changes in TH concentrations within the hypothalamus, with T3 eliciting a downregulation of hypothalamic AMP-activated protein kinase (AMPK), supporting the existence of a central action of peripheral TH. Altogether, these data suggest that peripherally administered TH modulate energy balance by various mechanisms; they also provide a unifying vision of the centrally mediated and the direct local metabolic effect of TH in the context of hyperthyroidism.https://www.mdpi.com/2072-6643/13/12/4204thyroid hormonesAMPKhypothalamusbrown adipose tissuebrowning |
| spellingShingle | Valentina Capelli Carmen Grijota-Martínez Nathalia R. V. Dragano Eval Rial-Pensado Johan Fernø Rubén Nogueiras Jens Mittag Carlos Diéguez Miguel López Orally Induced Hyperthyroidism Regulates Hypothalamic AMP-Activated Protein Kinase Nutrients thyroid hormones AMPK hypothalamus brown adipose tissue browning |
| title | Orally Induced Hyperthyroidism Regulates Hypothalamic AMP-Activated Protein Kinase |
| title_full | Orally Induced Hyperthyroidism Regulates Hypothalamic AMP-Activated Protein Kinase |
| title_fullStr | Orally Induced Hyperthyroidism Regulates Hypothalamic AMP-Activated Protein Kinase |
| title_full_unstemmed | Orally Induced Hyperthyroidism Regulates Hypothalamic AMP-Activated Protein Kinase |
| title_short | Orally Induced Hyperthyroidism Regulates Hypothalamic AMP-Activated Protein Kinase |
| title_sort | orally induced hyperthyroidism regulates hypothalamic amp activated protein kinase |
| topic | thyroid hormones AMPK hypothalamus brown adipose tissue browning |
| url | https://www.mdpi.com/2072-6643/13/12/4204 |
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