Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to weight-loss

ELife
Fredrick E HenryScott M Sternson

Abstract

Molecular and cellular processes in neurons are critical for sensing and responding to energy deficit states, such as during weight-loss. Agouti related protein (AGRP)-expressing neurons are a key hypothalamic population that is activated during energy deficit and increases appetite and weight-gain. Cell type-specific transcriptomics can be used to identify pathways that counteract weight-loss, and here we report high-quality gene expression profiles of AGRP neurons from well-fed and food-deprived young adult mice. For comparison, we also analyzed Proopiomelanocortin (POMC)-expressing neurons, an intermingled population that suppresses appetite and body weight. We find that AGRP neurons are considerably more sensitive to energy deficit than POMC neurons. Furthermore, we identify cell type-specific pathways involving endoplasmic reticulum-stress, circadian signaling, ion channels, neuropeptides, and receptors. Combined with methods to validate and manipulate these pathways, this resource greatly expands molecular insight into neuronal regulation of body weight, and may be useful for devising therapeutic strategies for obesity and eating disorders.

References

Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·C BrobergerT Hökfelt
Apr 9, 1999·Nature Neuroscience·T M HahnM W Schwartz
May 9, 2000·The Journal of Biological Chemistry·A S BanksM G Myers
Aug 3, 2001·Nature Cell Biology·T Xu, S M Bajjalieh
Oct 16, 2003·Molecular and Cellular Biology·Ann-Hwee LeeLaurie H Glimcher
Apr 6, 2004·Science·Sebastien G BouretRichard B Simerly
May 12, 2004·Brain Research. Molecular Brain Research·Jeremy S FrancisMatthew J During
Aug 4, 2004·Proceedings of the National Academy of Sciences of the United States of America·Sean CaenepeelGerard Manning
Dec 3, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Bernadett BodaDominique Muller
Dec 21, 2004·Nucleic Acids Research·Yunjia ChenJingchu Luo
Dec 22, 2005·Nature Neuroscience·Ken SuginoSacha B Nelson
Apr 11, 2006·Nature Medicine·Tadahiro KitamuraDomenico Accili
Jun 22, 2006·CNS & Neurological Disorders Drug Targets·Helgi B Schiöth
Jan 4, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·John D CahoyBen A Barres
Jul 11, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Deniz AtasoyScott M Sternson
Oct 11, 2008·PLoS Computational Biology·Jun YanChunxuan Shao
Mar 24, 2009·FEBS Letters·Long HeBo Yeon Kim
Apr 10, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Anthony N van den PolChristian Broberger
Sep 22, 2009·Journal of Neurochemistry·Claudia ColombritaAntonia Ratti
Jan 15, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jason A BartosJohannes W Hell
Jan 29, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jian QiuMartin J Kelly
Feb 20, 2010·International Journal of Cell Biology·Afshin SamaliSanjeev Gupta
Mar 4, 2010·Genome Biology·Mark D Robinson, Alicia Oshlack
Jan 7, 2011·Nature Neuroscience·Yexica AponteScott M Sternson
Mar 3, 2011·The Journal of Clinical Investigation·Michael J KrashesBradford B Lowell
May 17, 2011·Molecular Cancer Research : MCR·Hiroe KitaharaShinichi Miyagawa
Jun 18, 2011·Science·Hao A DuongCharles J Weitz
Aug 19, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Troy A RoepkeMartin J Kelly

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Citations

Jan 5, 2016·Cell Metabolism·Scott M SternsonShengjin Xu
Mar 16, 2016·Metabolism: Clinical and Experimental·Kenji SaitoYong Xu
Mar 24, 2016·Developmental Cell·Zhe Liu, Philipp J Keller
Aug 9, 2016·The Journal of Clinical Investigation·Jing CuiXiaohui Wu
Oct 30, 2016·European Journal of Pharmacology·Claudio FerranteLuigi Brunetti
Oct 4, 2016·Neuron·C Joseph BurnettMichael J Krashes
Nov 22, 2016·Nature Neuroscience·Henning FenselauBradford B Lowell
Feb 7, 2017·Nature Neuroscience·John N CampbellLinus T Tsai
Feb 25, 2017·Cell·Christoffer ClemmensenMatthias H Tschöp
Mar 30, 2017·Cell Reports·Renchao ChenYi Zhang
Jan 7, 2017·The Journal of Endocrinology·Roman A RomanovTibor Harkany
Oct 5, 2016·Nature·Alexander M HermanBenjamin R Arenkiel
Dec 7, 2018·British Journal of Pharmacology·Zhenyan HeKevin W Williams
Jan 13, 2018·Nature Reviews. Neuroscience·Warren W Pan, Martin G Myers
Feb 17, 2018·Nature Reviews. Neuroscience·Alexandre CaronLaurent Gautron
Feb 15, 2018·EMBO Reports·Aygul SubkhangulovaThomas E Willnow
Jun 8, 2018·Human Molecular Genetics·Merve OnculDeniz Atasoy
Nov 1, 2016·Nature Neuroscience·Alastair S GarfieldBradford B Lowell
Dec 4, 2019·Nature Communications·Harry MacKayRobert A Waterland
Nov 7, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xia LeiG William Wong
May 30, 2020·Genesis : the Journal of Genetics and Development·Yu HuZhonghua Lu
Sep 30, 2017·Nature Communications·Dollada SrisaiJulien A Sebag
Apr 5, 2018·Scientific Reports·Aditya S ShiraliM Luisa Iruela-Arispe
Aug 26, 2018·Nature Communications·Mar QuiñonesRuben Nogueiras
Oct 23, 2019·Proceedings of the National Academy of Sciences of the United States of America·Ben Jerry GonzalesAmi Citri
Jan 30, 2020·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Anna IdelevichRoland Baron
Apr 30, 2020·Biomolecules·Alexey A TinkovAnatoly V Skalny

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Datasets Mentioned

BETA
GSE68177
GSE52564

Methods Mentioned

BETA
immunoprecipitation
dissection
RNA-Seq
MDS
fluorescence activated cell sorting
GTPase
protein folding
smFISH
nuclear translocation
PCR

Software Mentioned

R
FIJI
Ingenuity Pathway Analysis ( IPA ) server
smFISH
UCSC genome browser
Python
Pomc
RNASeqPower
MATLAB scripts
voom

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