期刊
NATURE MEDICINE
卷 23, 期 5, 页码 623-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.4316
关键词
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资金
- Alexander von Humboldt Foundation
- Helmholtz Alliance ICEMED
- Helmholtz Initiative on Personalized Medicine iMed by Helmholtz Association
- Helmholtz cross-program topic Metabolic Dysfunction
- German Research Foundation [DFG-TS226/1-1, DFG-TS226/3-1, SFB1123]
- Nutripathos Project [ANR-15-CE14-0030]
- European Research Council ERC AdG HypoFlam [695054]
- DFG [He3260/8-1]
- EU FP7 Network DIABAT
- EU ITN Network TRAIN [721531]
- NIH [R01 AA023416, DK082724, R01DK099222, DK17844]
- American Diabetes Association
- Israeli Science Foundation
- European Research Council [340345]
- Swedish Research Council
- Knut and Alice Wallenberg Foundation
- Lundbeck Foundation [R210-2015-4001] Funding Source: researchfish
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 beta 3-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-alpha 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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