title: Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance.
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 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.
authors.affiliation: Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, A Coruña, Spain. m.lopez@usc.es
authors.forename: Miguel
authors.initials: M
authors.lastname: López
authors.forename: Luis
authors.initials: L
authors.lastname: Varela
authors.forename: María J
authors.initials: MJ
authors.lastname: Vázquez
authors.forename: Sergio
authors.initials: S
authors.lastname: Rodríguez-Cuenca
authors.forename: Carmen R
authors.initials: CR
authors.lastname: González
authors.forename: Vidya R
authors.initials: VR
authors.lastname: Velagapudi
authors.forename: Donald A
authors.initials: DA
authors.lastname: Morgan
authors.forename: Erik
authors.initials: E
authors.lastname: Schoenmakers
authors.forename: Khristofor
authors.initials: K
authors.lastname: Agassandian
authors.forename: Ricardo
authors.initials: R
authors.lastname: Lage
authors.forename: Pablo Blanco
authors.initials: PB
authors.lastname: Martínez de Morentin
authors.forename: Sulay
authors.initials: S
authors.lastname: Tovar
authors.forename: Rubén
authors.initials: R
authors.lastname: Nogueiras
authors.forename: David
authors.initials: D
authors.lastname: Carling
authors.forename: Christopher
authors.initials: C
authors.lastname: Lelliott
authors.forename: Rosalía
authors.initials: R
authors.lastname: Gallego
authors.forename: Matej
authors.initials: M
authors.lastname: Oresic
authors.forename: Krishna
authors.initials: K
authors.lastname: Chatterjee
authors.forename: Asish K
authors.initials: AK
authors.lastname: Saha
authors.forename: Kamal
authors.initials: K
authors.lastname: Rahmouni
authors.forename: Carlos
authors.initials: C
authors.lastname: Diéguez
authors.forename: Antonio
authors.initials: A
authors.lastname: Vidal-Puig
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D054369:Agouti-Related Protein / Q000235:genetics; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D002569:Cerulenin / Q000494:pharmacology; D004734:Energy Metabolism / Q000502:physiology*; D054872:Fatty Acid Synthesis Inhibitors / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D006963:Hyperphagia / Q000209:etiology; D006980:Hyperthyroidism / Q000150:complications / Q000378:metabolism; D007031:Hypothalamus / Q000201:enzymology*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D022722:Thermogenesis / Q000502:physiology; D013961:Thyroid Gland / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics; D013974:Thyroxine / Q000097:blood / Q000494:pharmacology; D014284:Triiodothyronine / Q000097:blood
chemical_list: C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D054872:Fatty Acid Synthesis Inhibitors; D005227:Fatty Acids; D012333:RNA, Messenger; D014284:Triiodothyronine; D002569:Cerulenin; D013973:Thyrotropin-Releasing Hormone; D011333:Pro-Opiomelanocortin; D055372:AMP-Activated Protein Kinases; D013974:Thyroxine
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