Journal article
Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance
Nature medicine, Vol.16(9), pp.1001-1008
09/2010
DOI: 10.1038/nm.2207
PMCID: PMC2935934
PMID: 20802499
Abstract
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 (TRs) in the VMH reverses the weight loss associated with hyperthyroidism. This regulatory mechanism depends on AMPK inactivation as genetic ablation 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 an important regulator of energy homeostasis.
Details
- Title: Subtitle
- Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance
- Creators
- Miguel López - Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela (A Coruña), 15782, SpainLuis Varela - Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela (A Coruña), 15782, SpainMaría J Vázquez - Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela (A Coruña), 15782, SpainSergio Rodríguez-Cuenca - Institute of Metabolic Science, Metabolic Research Laboratories, Addenbrooke’s Hospital, University of Cambridge, Cambridge, CB2 0QQ, UKCarmen R González - Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela (A Coruña), 15782, SpainVidya R Velagapudi - VTT Technical Research Centre of Finland, Tietotie 2, Espoo, FIN-02044, FinlandDonald A Morgan - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, 52242, USAErik Schoenmakers - Institute of Metabolic Science, Metabolic Research Laboratories, Addenbrooke’s Hospital, University of Cambridge, Cambridge, CB2 0QQ, UKKhristofor Agassandian - Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, Iowa, 52242, USARicardo Lage - Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela (A Coruña), 15782, SpainPablo B Martínez de Morentin - Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela (A Coruña), 15782, SpainSulay Tovar - Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela (A Coruña), 15782, SpainRubén Nogueiras - Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela (A Coruña), 15782, SpainDavid Carling - Cellular Stress Group, Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, Imperial College, London, W12 0NN, UKChristopher Lelliott - Department of Biosciences, AstraZeneca R&D, Mölndal, S-43183, SwedenRosalía Gallego - Department of Morphological Sciences, School of Medicine, University of Santiago de Compostela, 15782, SpainMatej Orešič - VTT Technical Research Centre of Finland, Tietotie 2, Espoo, FIN-02044, FinlandKrishna Chatterjee - Institute of Metabolic Science, Metabolic Research Laboratories, Addenbrooke’s Hospital, University of Cambridge, Cambridge, CB2 0QQ, UKAsish K Saha - Diabetes Research Unit, EBRC-827, Boston Medical Center, Boston, MA 02118, USAKamal Rahmouni - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, 52242, USACarlos Diéguez - Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela (A Coruña), 15782, SpainAntonio Vidal-Puig - Institute of Metabolic Science, Metabolic Research Laboratories, Addenbrooke’s Hospital, University of Cambridge, Cambridge, CB2 0QQ, UK
- Resource Type
- Journal article
- Publication Details
- Nature medicine, Vol.16(9), pp.1001-1008
- DOI
- 10.1038/nm.2207
- PMID
- 20802499
- PMCID
- PMC2935934
- NLM abbreviation
- Nat Med
- ISSN
- 1078-8956
- eISSN
- 1546-170X
- Language
- English
- Date published
- 09/2010
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040480402771
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