Thyroid hormones induce browning of white fat
- Noelia Martínez-Sánchez1,2,
- José M Moreno-Navarrete2,3,
- Cristina Contreras1,2,
- Eva Rial-Pensado1,2,
- Johan Fernø1,4,
- Rubén Nogueiras1,2,
- Carlos Diéguez1,2,
- José-Manuel Fernández-Real2,3⇑ and
- Miguel López1,2⇑
- 1Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain
- 2CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
- 3Department of Diabetes, Endocrinology and Nutrition, Hospital de Girona ‘Dr Josep Trueta’, Institut D’investigació Biomèdica de Girona (IdIBGi) and University of Girona, Girona, Spain
- 4Department of Clinical Science, KG Jebsen Center for Diabetes Research, University of Bergen, Bergen, Norway
- Correspondence should be addressed to J-M Fernández-Real or Miguel López; Email: jmfreal{at}idibgi.org or m.lopez{at}usc.es
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 T3 on browning. Finally, we also showed that the expression of browning genes in human WAT correlates with serum T4. Overall, these data indicate that THs induce browning of WAT and that this mechanism is mediated via the central effects of THs on energy balance.
- Received 20 November 2016
- Accepted 2 December 2016
- Made available online as an Accepted Preprint 2 December 2016
- © 2017 The authors
This work is licensed under a Creative Commons Attribution 3.0 Unported License.
