title: Thyroid hormones induce browning of white fat.
abstract: The canonical view about the effect of thyroid hormones (THs) on thermogenesis assumes that the hypothalamus acts merely as a modulator of the sympathetic outflow on brown adipose tissue (BAT). Recent data have challenged that vision by demonstrating that THs act on the ventromedial nucleus of the hypothalamus (VMH) to inhibit AMP-activated protein kinase (AMPK), which regulates the thermogenic program in BAT, leading to increased thermogenesis and weight loss. Current data have shown that in addition to activation of brown fat, the browning of white adipose tissue (WAT) might also be an important thermogenic mechanism. However, the possible central effects of THs on the browning of white fat remain unclear. Here, we show that 3,3',5,5' tetraiodothyroxyne (T4)-induced hyperthyroidism promotes a marked browning of WAT. Of note, central or VMH-specific administration of 3,3',5-triiodothyronine (T3) recapitulates that effect. The specific genetic activation of hypothalamic AMPK in the VMH reversed the central effect of T3on browning. Finally, we also showed that the expression of browning genes in human WAT correlates with serum T4Overall, these data indicate that THs induce browning of WAT and that this mechanism is mediated via the central effects of THs on energy balance.
authors.affiliation: Department of PhysiologyCIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn)Santiago de Compostela, Spain.
authors.forename: Noelia
authors.initials: N
authors.lastname: Martínez-Sánchez
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn)Santiago de Compostela, Spain.|Department of DiabetesEndocrinology and Nutrition, Hospital de Girona 'Dr Josep Trueta', Institut D'investigació Biomèdica de Girona (IdIBGi) and University of Girona, Girona, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Moreno-Navarrete
authors.affiliation: Department of PhysiologyCIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn)Santiago de Compostela, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Contreras
authors.affiliation: Department of PhysiologyCIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn)Santiago de Compostela, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Rial-Pensado
authors.affiliation: Department of PhysiologyCIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.|Department of Clinical ScienceKG Jebsen Center for Diabetes Research, University of Bergen, Bergen, Norway.
authors.forename: Johan
authors.initials: J
authors.lastname: Fernø
authors.affiliation: Department of PhysiologyCIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn)Santiago de Compostela, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Nogueiras
authors.affiliation: Department of PhysiologyCIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn)Santiago de Compostela, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Diéguez
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn)Santiago de Compostela, Spain jmfreal@idibgi.org m.lopez@usc.es.|Department of DiabetesEndocrinology and Nutrition, Hospital de Girona 'Dr Josep Trueta', Institut D'investigació Biomèdica de Girona (IdIBGi) and University of Girona, Girona, Spain.
authors.forename: José-Manuel
authors.initials: JM
authors.lastname: Fernández-Real
authors.affiliation: Department of PhysiologyCIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain jmfreal@idibgi.org m.lopez@usc.es.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn)Santiago de Compostela, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: López
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006980:Hyperthyroidism / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D022722:Thermogenesis / Q000187:drug effects; D013974:Thyroxine / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology*; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism
chemical_list: D014284:Triiodothyronine; D013974:Thyroxine
keywords: AMPK; browning; thyroid hormones; white adipose tissue