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J Endocrinol. 2017 Feb;232(2):351-362. doi: 10.1530/JOE-16-0425. Epub 2016 Dec 2.

Thyroid hormones induce browning of white fat.

Author information

1
Department of PhysiologyCIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.
2
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn)Santiago de Compostela, Spain.
3
Department of DiabetesEndocrinology and Nutrition, Hospital de Girona 'Dr Josep Trueta', Institut D'investigació Biomèdica de Girona (IdIBGi) and University of Girona, Girona, Spain.
4
Department of Clinical ScienceKG Jebsen Center for Diabetes Research, University of Bergen, Bergen, Norway.
5
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn)Santiago de Compostela, Spain jmfreal@idibgi.org m.lopez@usc.es.
6
Department of PhysiologyCIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain jmfreal@idibgi.org m.lopez@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.

KEYWORDS:

AMPK; browning; thyroid hormones; white adipose tissue

PMID:
27913573
PMCID:
PMC5292977
DOI:
10.1530/JOE-16-0425
[Indexed for MEDLINE]
Free PMC Article

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