@article{dd4fa212f6fe4964abdd8c141c87834b,
title = "Dietary Intake Regulates the Circulating Inflammatory Monocyte Pool",
abstract = "Caloric restriction is known to improve inflammatory and autoimmune diseases. However, the mechanisms by which reduced caloric intake modulates inflammation are poorly understood. Here we show that short-term fasting reduced monocyte metabolic and inflammatory activity and drastically reduced the number of circulating monocytes. Regulation of peripheral monocyte numbers was dependent on dietary glucose and protein levels. Specifically, we found that activation of the low-energy sensor 5′-AMP-activated protein kinase (AMPK) in hepatocytes and suppression of systemic CCL2 production by peroxisome proliferator-activator receptor alpha (PPARα) reduced monocyte mobilization from the bone marrow. Importantly, we show that fasting improves chronic inflammatory diseases without compromising monocyte emergency mobilization during acute infectious inflammation and tissue repair. These results reveal that caloric intake and liver energy sensors dictate the blood and tissue immune tone and link dietary habits to inflammatory disease outcome.",
keywords = "AMPK, CCL2, Caloric restriction, PPARα, fasting, inflammation, inflammatory disease, liver, metabolism, monocyte",
author = "Stefan Jordan and Navpreet Tung and M. Casanova-Acebes and Christie Chang and Claudia Cantoni and Dachuan Zhang and Wirtz, {Theresa H.} and Shruti Naik and Rose, {Samuel A.} and Brocker, {Chad N.} and Anastasiia Gainullina and Daniel Hornburg and Sam Horng and Maier, {Barbara B.} and P. Cravedi and D. LeRoith and Gonzalez, {Frank J.} and F. Meissner and J. Ochando and A. Rahman and Chipuk, {Jerry E.} and Artyomov, {Maxim N.} and Frenette, {Paul S.} and L. Piccio and Berres, {Marie Luise} and Gallagher, {Emily J.} and Miriam Merad",
note = "Funding Information: We thank J. Agudo, S. Offermanns, C. Buettner, S. Fried, T. E. McGraw, A. W. Ferrante and the Merad laboratory for helpful discussions. We thank J. LeBerichel for technical assistance, A. Lansky for submission of the IRB application, the Flow Cytometry facility for technical support, the Human immune monitoring core for assistance with the multiplex assay, M. Davila for processing CyTOF data, M. Serasinghe for help with metabolic measurements in monocytes, the Stable Isotope & Metabolomics core at Albert Einstein College of Medicine for assistance with blood metabolite measurements, S. Hatem for assistance with phlebotomy and all participants of the human fasting experiment. We are grateful to Y. Belkaid for giving us the opportunity to use her laboratory at NIH and N. Bouladoux for assistance. We thank Wiegand von Hartmann GBR for designing the graphical abstract. Supported by the NIH (R01 CA154947, U24 AI118644, U19 AI128949 to M.M. and K08CA190770 to E.J.G), The Tisch Cancer Institute (Junior Scientist Award to E.J.G), and the German Research Council (DFG) (SFB-TRR57 P07 to M.-L.B, JO 1216/1-1 to S.J.). S.J. conceived the study, designed, performed and analyzed experiments and wrote the manuscript. N.T. M.C.A. C.C. Cl.C. D.Z. T.H.W. S.N. D.H. S. H. B.B.M. A.R. and F.M. performed experiments and analyzed data. S.A.R. A.G. and M.N.A. analyzed the RNA-seq data. J.E.C. D.L. and P.S.F. provided intellectual expertise. C.N.B. P.C. and F.J.G. provided mice and intellectual expertise. L.P. and M.-L.B. designed and funded experiments. E.J.G. designed, performed, analyzed and funded experiments and wrote the manuscript. M.M. supervised and funded the study and wrote the manuscript. All authors discussed the data and edited the manuscript. The authors declare no competing interests. Funding Information: We thank J. Agudo, S. Offermanns, C. Buettner, S. Fried, T. E. McGraw, A. W. Ferrante and the Merad laboratory for helpful discussions. We thank J. LeBerichel for technical assistance, A. Lansky for submission of the IRB application, the Flow Cytometry facility for technical support, the Human immune monitoring core for assistance with the multiplex assay, M. Davila for processing CyTOF data, M. Serasinghe for help with metabolic measurements in monocytes, the Stable Isotope & Metabolomics core at Albert Einstein College of Medicine for assistance with blood metabolite measurements, S. Hatem for assistance with phlebotomy and all participants of the human fasting experiment. We are grateful to Y. Belkaid for giving us the opportunity to use her laboratory at NIH and N. Bouladoux for assistance. We thank Wiegand von Hartmann GBR for designing the graphical abstract. Supported by the NIH ( R01 CA154947 , U24 AI118644 , U19 AI128949 to M.M. and K08CA190770 to E.J.G), The Tisch Cancer Institute (Junior Scientist Award to E.J.G), and the German Research Council (DFG) ( SFB-TRR57 P07 to M.-L.B, JO 1216/1-1 to S.J.). Publisher Copyright: {\textcopyright} 2019",
year = "2019",
month = aug,
day = "22",
doi = "10.1016/j.cell.2019.07.050",
language = "English (US)",
volume = "178",
pages = "1102--1114.e17",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",
}