Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.

Original publication

DOI

10.1016/j.cmet.2017.06.014

Type

Journal article

Journal

Cell Metab

Publication Date

05/07/2017

Volume

26

Pages

212 - 229.e12

Keywords

AMPK, BAT, ER stress, JNK1, SF1, VMH, autonomic nervous system, ceramides, liver, thyroid hormones, Adipose Tissue, Brown, Animals, Energy Metabolism, Hypothalamus, Lipid Metabolism, Liver, Male, Mice, Inbred C57BL, Mitogen-Activated Protein Kinase 8, Rats, Rats, Sprague-Dawley, Signal Transduction, Thermogenesis, Thyroid Hormones, Triiodothyronine