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Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance
Department of Physiology, School of Medicine, University of Santiago de Compostela, Santiago de Compostela A Coruña, Spain; Centro de Investigacion Biomedica en Red de la Fisiopatologia de la Obesidad y Nutricion, A Coruña, Spain; Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
Department of Physiology, School of Medicine, University of Santiago de Compostela, Santiago de Compostela A Coruña, Spain; Centro de Investigacion Biomedica en Red de la Fisiopatologia de la Obesidad y Nutricion, A Coruña, Spain.
Department of Physiology, School of Medicine, University of Santiago de Compostela, Santiago de Compostela A Coruña, Spain; Centro de Investigacion Biomedica en Red de la Fisiopatologia de la Obesidad y Nutricion, A Coruña, Spain.
Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
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2010 (English)In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 16, no 9, p. 1001-1008Article in journal (Refereed) Published
Abstract [en]

Thyroid hormones have widespread cellular effects; however it is unclear whether their effects on the central nervous system (CNS) contribute to global energy balance. Here we demonstrate that either whole-body hyperthyroidism or central administration of triiodothyronine (T3) decreases the activity of hypothalamic AMP-activated protein kinase (AMPK), increases sympathetic nervous system (SNS) activity and upregulates thermogenic markers in brown adipose tissue (BAT). Inhibition of the lipogenic pathway in the ventromedial nucleus of the hypothalamus (VMH) prevents CNS-mediated activation of BAT by thyroid hormone and reverses the weight loss associated with hyperthyroidism. Similarly, inhibition of thyroid hormone receptors in the VMH reverses the weight loss associated with hyperthyroidism. This regulatory mechanism depends on AMPK inactivation, as genetic inhibition of this enzyme in the VMH of euthyroid rats induces feeding-independent weight loss and increases expression of thermogenic markers in BAT. These effects are reversed by pharmacological blockade of the SNS. Thus, thyroid hormone-induced modulation of AMPK activity and lipid metabolism in the hypothalamus is a major regulator of whole-body energy homeostasis.

Place, publisher, year, edition, pages
Nature Publishing Group, 2010. Vol. 16, no 9, p. 1001-1008
National Category
Medical and Health Sciences Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:oru:diva-63637DOI: 10.1038/nm.2207ISI: 000281622900029PubMedID: 20802499Scopus ID: 2-s2.0-77956431307OAI: oai:DiVA.org:oru-63637DiVA, id: diva2:1169202
Funder
Wellcome trust, 080237 065326/Z/01/Z
Note

Funding agencies:

UK Medical Research Council G0802051

Available from: 2017-12-22 Created: 2017-12-22 Last updated: 2018-05-02Bibliographically approved

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