1. Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis.
- Author
-
Fischer K, Ruiz HH, Jhun K, Finan B, Oberlin DJ, van der Heide V, Kalinovich AV, Petrovic N, Wolf Y, Clemmensen C, Shin AC, Divanovic S, Brombacher F, Glasmacher E, Keipert S, Jastroch M, Nagler J, Schramm KW, Medrikova D, Collden G, Woods SC, Herzig S, Homann D, Jung S, Nedergaard J, Cannon B, Tschöp MH, Müller TD, and Buettner C
- Subjects
- Adaptation, Physiological, Adipocytes drug effects, Adipose Tissue drug effects, 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, Mice, Mice, Knockout, Receptors, Cell Surface genetics, Thermogenesis genetics, Uncoupling Protein 1 genetics, Adipocytes metabolism, Adipose Tissue metabolism, Macrophages immunology, Norepinephrine metabolism, Receptors, Adrenergic, beta-3 metabolism, Thermogenesis immunology, Tyrosine 3-Monooxygenase genetics
- Abstract
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.- Published
- 2017
- Full Text
- View/download PDF