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Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance

López, Miguel (author)
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
Varela, Luis (author)
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
Vázquez, María J (author)
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
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Rodríguez-Cuenca, Sergio (author)
Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
González, Carmen R. (author)
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
Velagapudi, Vidya R. (author)
Technical Research Centre of Finland (VTT), Espoo, Finland
Morgan, Donald A. (author)
Department of Internal Medicine, University of Iowa Carver, College of Medicine, Iowa City IA, United States
Schoenmakers, Erik (author)
Department of Internal Medicine, University of Iowa Carver, College of Medicine, Iowa City IA, United States
Agassandian, Khristofor (author)
Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City IA, United States
Lage, Ricardo (author)
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
Martínez de Morentin, Pablo Blanco (author)
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
Tovar, Sulay (author)
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
Nogueiras, Rubén (author)
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
Carling, David (author)
Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, Imperial College, London, United Kingdom
Lelliott, Christopher (author)
Department of Biosciences, AstraZeneca Research and Development, Mölndal, Sweden
Gallego, Rosalía (author)
Department of Morphological Sciences, School of Medicine, University of Santiago de Compostela, A Coruña, Spain
Oresic, Matej, 1967- (author)
Örebro universitet,Institutionen för medicinska vetenskaper,Technical Research Centre of Finland (VTT), Espoo, Finland
Chatterjee, Krishna (author)
Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
Saha, Asish K (author)
Diabetes Research Unit, Boston Medical Center, Boston MA, United States
Rahmouni, Kamal (author)
Department of Internal Medicine, University of Iowa Carver, College of Medicine, Iowa City IA, United States
Diéguez, Carlos (author)
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
Vidal-Puig, Antonio (author)
Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
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 (creator_code:org_t)
2010-08-29
2010
English.
In: Nature Medicine. - : Nature Publishing Group. - 1078-8956 .- 1546-170X. ; 16:9, s. 1001-1008
Related links:
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)

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