Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis

Katrin Fischer; Henry H Ruiz; Kevin Jhun; Brian Finan; Douglas J Oberlin; Verena van der Heide; Anastasia V Kalinovich; Natasa Petrovic; Yochai Wolf; Christoffer Clemmensen; Andrew C Shin; Senad Divanovic; Frank Brombacher; Elke Glasmacher; Susanne Keipert; Martin Jastroch; Joachim Nagler; Karl-Werner Schramm; Dasa Medrikova; Gustav Collden; Stephen C Woods; Stephan Herzig; Dirk Homann; Steffen Jung; Jan Nedergaard; Barbara Cannon; Matthias H Tschöp; Timo D Müller; Christoph Buettner

doi:10.1038/nm.4316

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Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis

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Peer reviewed

Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis

Katrin Fischer, Henry H Ruiz, Kevin Jhun, Brian Finan, Douglas J Oberlin, Verena van der Heide, Anastasia V Kalinovich, Natasa Petrovic, Yochai Wolf, Christoffer Clemmensen, …

Nature medicine, Vol.23(5), pp.623-630

05/2017

DOI: https://doi.org/10.1038/nm.4316

PMCID: PMC5420449

PMID: 28414329

Abstract

Adaptation, Physiological

Adipocytes - drug effects

Adipocytes - metabolism

Adipose Tissue - drug effects

Adipose Tissue - metabolism

Adipose Tissue, Brown - drug effects

Adipose Tissue, Brown - metabolism

Adipose Tissue, White - drug effects

Adipose Tissue, White - metabolism

Animals

Blotting, Western

Body Composition - immunology

Catecholamines - metabolism

Cell Differentiation

Culture Media, Conditioned

Energy Metabolism - genetics

Flow Cytometry

Fluorescent Antibody Technique

Gene Expression Profiling

Interleukin-4 - immunology

Interleukin-4 - pharmacology

Macrophages - drug effects

Macrophages - immunology

Mice

Mice, Knockout

Norepinephrine - metabolism

Receptors, Adrenergic, beta-3 - metabolism

Receptors, Cell Surface - genetics

Thermogenesis - genetics

Thermogenesis - immunology

Tyrosine 3-Monooxygenase - genetics

Uncoupling Protein 1 - genetics

Adaptive thermogenesis is the process of heat generation in response to cold stimulation. It is under the control of the sympathetic nervous system, whose chief effector is the catecholamine norepinephrine (NE). NE enhances thermogenesis through β3-adrenergic receptors to activate brown adipose tissue and by 'browning' white adipose tissue. Recent studies have reported that alternative activation of macrophages in response to interleukin (IL)-4 stimulation induces the expression of tyrosine hydroxylase (TH), a key enzyme in the catecholamine synthesis pathway, and that this activation provides an alternative source of locally produced catecholamines during the thermogenic process. Here we report that the deletion of Th in hematopoietic cells of adult mice neither alters energy expenditure upon cold exposure nor reduces browning in inguinal adipose tissue. Bone marrow-derived macrophages did not release NE in response to stimulation with IL-4, and conditioned media from IL-4-stimulated macrophages failed to induce expression of thermogenic genes, such as uncoupling protein 1 (Ucp1), in adipocytes cultured with the conditioned media. Furthermore, chronic treatment with IL-4 failed to increase energy expenditure in wild-type, Ucp1 and interleukin-4 receptor-α double-negative (Il4ra ) mice. In agreement with these findings, adipose-tissue-resident macrophages did not express TH. Thus, we conclude that alternatively activated macrophages do not synthesize relevant amounts of catecholamines, and hence, are not likely to have a direct role in adipocyte metabolism or adaptive thermogenesis.

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Title: Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis
Creators: Katrin Fischer - Division of Metabolic Diseases, Department of Medicine, Technische Universität München, 80333 Munich, Germany
Henry H Ruiz - Diabetes, Metabolism and Obesity Institute, Icahn School of Medicine at Mount Sinai, NY 10029, USA
Kevin Jhun - Diabetes, Metabolism and Obesity Institute, Icahn School of Medicine at Mount Sinai, NY 10029, USA
Brian Finan - Division of Metabolic Diseases, Department of Medicine, Technische Universität München, 80333 Munich, Germany
Douglas J Oberlin - Diabetes, Metabolism and Obesity Institute, Icahn School of Medicine at Mount Sinai, NY 10029, USA
Verena van der Heide - Diabetes, Metabolism and Obesity Institute, Icahn School of Medicine at Mount Sinai, NY 10029, USA
Anastasia V Kalinovich - Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden
Natasa Petrovic - Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden
Yochai Wolf - Weizmann Institute of Science Department of Immunology, 76100 Rehovot, Israel
Christoffer Clemmensen - Division of Metabolic Diseases, Department of Medicine, Technische Universität München, 80333 Munich, Germany
Andrew C Shin - Diabetes, Metabolism and Obesity Institute, Icahn School of Medicine at Mount Sinai, NY 10029, USA
Senad Divanovic - Department of Pediatrics, Division of Immunobiology, Cincinnati Children's Hospital Medical Center, OH 45229 Cincinnati, USA
Frank Brombacher - International Center for Genetic Engineering and Biotechnology, Cape Town component & University of Cape Town, IDM, Division Immunology & SAMRC, South Africa
Elke Glasmacher - Institute for Diabetes and Obesity, Helmholtz Diabetes Center (HDC) at Helmholtz Zentrum München and German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany
Susanne Keipert - Institute for Diabetes and Obesity, Helmholtz Diabetes Center (HDC) at Helmholtz Zentrum München and German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany
Martin Jastroch - Department of Animal Physiology, Faculty of Biology, Philipps University of Marburg, 35032 Marburg, Germany
Joachim Nagler - Molecular Exposomics, Helmholtz Zentrum München, German National Diabetes Center (DZD), 85764 Neuherberg, Germany
Karl-Werner Schramm - Molecular Exposomics, Helmholtz Zentrum München, German National Diabetes Center (DZD), 85764 Neuherberg, Germany
Dasa Medrikova - Institute for Diabetes and Cancer (IDC), Helmholtz Zentrum München, German National Diabetes Center (DZD), 85764 Neuherberg, Germany, and Joint IDC-Heidelberg Translational Diabetes Program, Inner Medicine I, Heidelberg University Hospital, 69120 Heidelberg, Germany
Gustav Collden - Division of Metabolic Diseases, Department of Medicine, Technische Universität München, 80333 Munich, Germany
Stephen C Woods - Metabolic Diseases Institute, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, OH 45237 Cincinnati, USA
Stephan Herzig - Institute for Diabetes and Cancer (IDC), Helmholtz Zentrum München, German National Diabetes Center (DZD), 85764 Neuherberg, Germany, and Joint IDC-Heidelberg Translational Diabetes Program, Inner Medicine I, Heidelberg University Hospital, 69120 Heidelberg, Germany
Dirk Homann - Diabetes, Metabolism and Obesity Institute, Icahn School of Medicine at Mount Sinai, NY 10029, USA
Steffen Jung - Weizmann Institute of Science Department of Immunology, 76100 Rehovot, Israel
Jan Nedergaard - Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden
Barbara Cannon - Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden
Matthias H Tschöp - Division of Metabolic Diseases, Department of Medicine, Technische Universität München, 80333 Munich, Germany
Timo D Müller - Institute for Diabetes and Obesity, Helmholtz Diabetes Center (HDC) at Helmholtz Zentrum München and German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany
Christoph Buettner - Department of Medicine, Icahn School of Medicine at Mount Sinai, NY 10029, USA
Publication Details: Nature medicine, Vol.23(5), pp.623-630
Date published: 05/2017
Grant note: R01 DK099222 / NIDDK NIH HHS R01 AI093637 / NIAID NIH HHS P30 DK020541 / NIDDK NIH HHS R01 AA023416 / NIAAA NIH HHS 340345 / European Research Council R01 DK017844 / NIDDK NIH HHS R03 DK082724 / NIDDK NIH HHS R37 DK017844 / NIDDK NIH HHS
Academic Unit: Medicine - Endocrinology, Metabolism and Nutrition (RWJMS)
Language: English
Resource Type: Journal article
Identifiers: 991031665310504646