Program in Molecular Medicine; UMass Metabolic Network; Davis Lab
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
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.
thyroid hormones, VMH, SF1, AMPK, ceramides, ER stress, JNK1, autonomic nervous system, liver, BAT
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Copyright © 2017 The Authors. Open Access funded by European Research Council.
DOI of Published Version
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
Martinez-Sanchez, Noelia; Davis, Roger J.; and Lopez, Miguel, "Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance" (2017). UMass Metabolic Network Publications. 129.
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