Deciphering an AgRP-serotoninergic neural circuit in distinct control of energy metabolism from feeding.

Nature Communications
Yong HanQi Wu

Abstract

Contrasting to the established role of the hypothalamic agouti-related protein (AgRP) neurons in feeding regulation, the neural circuit and signaling mechanisms by which they control energy expenditure remains unclear. Here, we report that energy expenditure is regulated by a subgroup of AgRP neurons that send non-collateral projections to neurons within the dorsal lateral part of dorsal raphe nucleus (dlDRN) expressing the melanocortin 4 receptor (MC4R), which in turn innervate nearby serotonergic (5-HT) neurons. Genetic manipulations reveal a bi-directional control of energy expenditure by this circuit without affecting food intake. Fiber photometry and electrophysiological results indicate that the thermo-sensing MC4RdlDRN neurons integrate pre-synaptic AgRP signaling, thereby modulating the post-synaptic serotonergic pathway. Specifically, the MC4RdlDRN signaling elicits profound, bi-directional, regulation of body weight mainly through sympathetic outflow that reprograms mitochondrial bioenergetics within brown and beige fat while feeding remains intact. Together, we suggest that this AgRP neural circuit plays a unique role in persistent control of energy expenditure and body weight, hinting next-generation therapeutic app...Continue Reading

References

Jan 15, 1986·The Journal of Comparative Neurology·H ImaiS T Kitai
Oct 12, 2000·Proceedings of the National Academy of Sciences of the United States of America·L Ste MarieR D Palmiter
Oct 3, 2002·Neuropeptides·A A Butler, R D Cone
Mar 29, 2003·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·C J SmallS R Bloom
Jul 21, 2004·Neuroscience·A Bratincsák, M Palkovits
Apr 28, 2005·Nature Neuroscience·Roger D Cone
Aug 16, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Gavin A BewickStephen R Bloom
Sep 15, 2005·Nature Neuroscience·Eva GroppJens C Brüning
Oct 28, 2005·Proceedings of the National Academy of Sciences of the United States of America·Michael M ScottEvan S Deneris
Dec 7, 2005·Cell Metabolism·Katherine E WortleyMark W Sleeman
Jan 19, 2006·Proceedings of the National Academy of Sciences of the United States of America·Bernat KocsisAttila Sik
Sep 12, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Qi WuRichard D Palmiter
Jan 23, 2009·Nature Neuroscience·Qingchun TongBradford B Lowell
Apr 10, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Anthony N van den PolChristian Broberger
Oct 5, 2010·Neuroscience·J V Schweimer, M A Ungless
Feb 1, 1946·The Anatomical Record·M ABERCROMBIE
Jan 7, 2011·Nature Neuroscience·Yexica AponteScott M Sternson
Mar 3, 2011·The Journal of Clinical Investigation·Michael J KrashesBradford B Lowell
Dec 30, 2011·Nature Methods·Matthias H TschöpEric Ravussin
Mar 16, 2012·Nature·Qi WuRichard D Palmiter
Jul 18, 2012·Nature·Deniz AtasoyScott M Sternson
Jan 22, 2013·ACS Chemical Neuroscience·Rodrigo Andrade, Samir Haj-Dahmane
Aug 22, 2013·Proceedings of the National Academy of Sciences of the United States of America·Qi WuRichard D Palmiter
Feb 4, 2014·Nature·Michael J KrashesBradford B Lowell
Mar 25, 2014·Neuron·Zhixiang LiuMinmin Luo
Jun 9, 2014·Nature Neuroscience·Eric D BerglundJoel K Elmquist

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Citations

Sep 7, 2021·Physiological Reviews·Alan G WattsWolfgang Langhans
Oct 17, 2021·The European Journal of Neuroscience·Ayden GouveiaSophie M Steculorum

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