Ketogenesis activates metabolically protective γδ T cells in visceral adipose tissue.

Nature Metabolism
Emily L GoldbergVishwa Deep Dixit

Abstract

Ketone bodies are essential alternative fuels that allow humans to survive periods of glucose scarcity induced by starvation and prolonged exercise. A widely used ketogenic diet (KD), which is extremely high in fat with very low carbohydrates, drives the host into using β-hydroxybutyrate for the production of ATP and lowers NLRP3-mediated inflammation. However, the extremely high fat composition of KD raises the question of how ketogenesis affects adipose tissue to control inflammation and energy homeostasis. Here, by using single-cell RNA sequencing of adipose-tissue-resident immune cells, we show that KD expands metabolically protective γδ T cells that restrain inflammation. Notably, long-term ad libitum KD feeding in mice causes obesity, impairs metabolic health and depletes the adipose-resident γδ T cells. In addition, mice lacking γδ T cells have impaired glucose homeostasis. Our results suggest that γδ T cells are mediators of protective immunometabolic responses that link fatty acid-driven fuel use to reduced adipose tissue inflammation.

References

Nov 1, 1996·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J SastreJ Viña
Dec 19, 2003·Nucleic Acids Research·Donna KarolchikW James Kent
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Jan 13, 2006·Nature·Sanjeev MariathasanVishva M Dixit
Jul 20, 2006·Annual Review of Nutrition·George F Cahill
Dec 15, 2006·Nature·Gökhan S Hotamisligil
Jan 4, 2007·The Journal of Clinical Investigation·Carey N LumengAlan R Saltiel
Feb 15, 2007·American Journal of Physiology. Endocrinology and Metabolism·Adam R KennedyEleftheria Maratos-Flier
Jan 19, 2010·Annual Review of Pathology·Jean-Philippe CoppéJudith Campisi
Jun 29, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hyunwon YangVishwa Deep Dixit
Nov 3, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Luis A ZúñigaEugene C Butcher
Jan 11, 2011·Nature Medicine·Bolormaa VandanmagsarVishwa Deep Dixit
Apr 2, 2011·American Journal of Physiology. Gastrointestinal and Liver Physiology·Joel R GarbowPeter A Crawford
May 7, 2011·Bioinformatics·Arthur LiberzonJill P Mesirov
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Jul 21, 2012·Nature Immunology·Thirumala-Devi Kanneganti, Vishwa Deep Dixit
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Jan 9, 2014·American Journal of Physiology. Endocrinology and Metabolism·Johanne H EllenbroekEelco J P de Koning
Aug 17, 2014·Aging·Clare EdwardsPatrick C Bradshaw
Nov 12, 2014·Immunology and Cell Biology·C PagetM J Smyth
Nov 15, 2014·Journal of Leukocyte Biology·Pooja MehtaC Wayne Smith
Mar 19, 2015·PloS One·Anne E CostanzoJulie M Jameson
Jul 19, 2015·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Jonathan M Mudge, Jennifer Harrow
Jul 21, 2015·Nature Medicine·Andrew J GentlesAsh A Alizadeh
Sep 27, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Baojun ZhangYuan Zhuang
Apr 23, 2016·Molecular Cell·Zhongyu XieYingming Zhao
Mar 2, 2017·Cell Reports·Emily L GoldbergVishwa Deep Dixit
Apr 12, 2017·Neurochemical Research·Timothy A SimeoneJong M Rho
Sep 7, 2017·Cell Metabolism·Megan N RobertsJose Alberto Lopez-Dominguez
Sep 7, 2017·Cell Metabolism·John C NewmanEric Verdin
Sep 19, 2017·Nature Reviews. Immunology·Morten M NielsenWendy L Havran

❮ Previous
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Citations

Feb 1, 2020·Nature Reviews. Endocrinology·Claire Greenhill
Jun 10, 2020·Reviews in Endocrine & Metabolic Disorders·Borja Bandera-MerchanFrancisco J Tinahones
Aug 28, 2020·Frontiers in Immunology·Flavian Thelen, Deborah A Witherden
Oct 6, 2020·Oxidative Medicine and Cellular Longevity·Patrick C BradshawWilliam M Curtis
Jul 23, 2020·Nature Metabolism·Brianna J Stubbs, John C Newman
Dec 8, 2020·Frontiers in Cardiovascular Medicine·Ibrahim AlZaimAhmed F El-Yazbi
Jan 1, 2021·International Journal of Molecular Sciences·Thomas Ho-Yin Lee, Suk-Yu Yau
Oct 23, 2020·International Journal of Molecular Sciences·Xavier Remesar, Marià Alemany
Dec 29, 2020·American Journal of Physiology. Cell Physiology·Tatsuo KawaiRosario Scalia
Oct 16, 2020·Nature Reviews. Immunology·Julie C RibotBruno Silva-Santos
Apr 13, 2021·Journal of Cardiovascular Pharmacology and Therapeutics·Emir M MuzurovićDimitri P Mikhailidis
Feb 2, 2021·Endocrine Reviews·Adil Rasheed, Katey J Rayner
Jun 9, 2021·Nature Reviews. Immunology·Elisa CarrascoMaria Mittelbrunn
Jul 3, 2021·Nutrients·Lucilla CrudeleAntonio Moschetta
Sep 3, 2021·Cell Metabolism·Emily L GoldbergVishwa Deep Dixit
Aug 18, 2021·Cancer Discovery·Lisa DerosaLaurence Zitvogel
Oct 3, 2021·Biological Chemistry·Maike Willers, Dorothee Viemann
Nov 7, 2021·Nature Reviews. Immunology·W V Trim, L Lynch

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Methods Mentioned

BETA
fluorescence-activated cell sorting
scRNA-seq
flow cytometry
FACS
PMA
Confocal microscopy
RNA-seq
single-cell sequencing
environmental stress
PCA

Software Mentioned

GSEA
FlowJo
fgsea GSEA ) R - package
STAR aligner
Efat
Morpheus
house Python script
R
Cellranger
Cell Ranger Single - Cell Software Suite

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