UMMS Affiliation

Program in Molecular Medicine; UMass Metabolic Network; Davis Lab

Date

7-5-2017

Document Type

Article

Disciplines

Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology

Abstract

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 AMPKalpha1 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.

Rights and Permissions

Copyright © 2017 The Authors. Open Access funded by European Research Council. Citation: Cell Metab. 2017 Jul 5;26(1):212-229.e12. doi: 10.1016/j.cmet.2017.06.014. Link to article on publisher's site

Comments

Full list of authors omitted for brevity. For full list see article.

Related Resources

Link to Article in PubMed

Keywords

thyroid hormones, VMH, SF1, AMPK, ceramides, ER stress, JNK1, autonomic nervous system, liver, BAT

PubMed ID

28683288

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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