Dietary Intake Regulates the Circulating Inflammatory Monocyte Pool

Stefan Jordan, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA. Electronic address: stefan.jordan@mssm.edu.
Navpreet Tung, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Maria Casanova-Acebes, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Christie Chang, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Claudia Cantoni, Department of Neurology, Washington University School of Medicine, 660 S Euclid Avenue, St. Louis, MO 63110, USA.Follow
Dachuan Zhang, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Department of Cell Biology, Albert Einstein College of Medicine, 1301 Morris Park Avenue, The Bronx, NY 10461, USA.
Theresa H. Wirtz, Department of Internal Medicine III, University Hospital, RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
Shruti Naik, Department of Pathology, and Ronald O. Perelman Department of Dermatology, NYU School of Medicine, 240 East 38(th) Street, New York, NY 10016, USA.
Samuel A. Rose, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Chad N. Brocker, Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 37, Bethesda, MD 20892, USA.
Anastasiia Gainullina, Department of Pathology & Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA; Computer Technologies Department, ITMO University, Kronverksky 49, Saint Petersburg, Russian Federation.
Daniel Hornburg, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Sam Horng, Department of Neurology and Neuroscience, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Barbara B. Maier, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Paolo Cravedi, The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Derek LeRoith, Division of Endocrinology, Diabetes and Bone Diseases, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Frank J. Gonzalez, Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 37, Bethesda, MD 20892, USA.
Felix Meissner, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Jordi Ochando, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Adeeb Rahman, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Jerry E. Chipuk, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Maxim N. Artyomov, Department of Pathology & Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Paul S. Frenette, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Department of Cell Biology, Albert Einstein College of Medicine, 1301 Morris Park Avenue, The Bronx, NY 10461, USA.
Laura Piccio, Department of Neurology, Washington University School of Medicine, 660 S Euclid Avenue, St. Louis, MO 63110, USA; Brain and Mind Centre, University of Sydney, 94 Mallett Street, Camperdown NSW 2050, Australia.
Marie-Luise Berres, Department of Internal Medicine III, University Hospital, RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
Emily J. Gallagher, Division of Endocrinology, Diabetes and Bone Diseases, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Miriam Merad, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA. Electronic address: miriam.merad@mssm.edu.

Document Type

Article

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

Medical Subject Headings

AMP-Activated Protein Kinases (metabolism); Adult; Animals; Antigens, Ly (metabolism); Bone Marrow Cells (cytology, metabolism); Caloric Restriction; Chemokine CCL2 (deficiency, genetics, metabolism); Female; Hepatocytes (cytology, metabolism); Humans; Inflammation (metabolism, pathology); Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocytes (cytology, metabolism); PPAR alpha (deficiency, genetics, metabolism)

Publication Date

8-22-2019

Publication Title

Cell

E-ISSN

1097-4172

Volume

178

Issue

5

First Page

1102

Last Page

1114.e17

PubMed ID

31442403

Digital Object Identifier (DOI)

10.1016/j.cell.2019.07.050

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