Document Detail


Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis.
MedLine Citation:
PMID:  22101429     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
All homeotherms use thermogenesis to maintain their core body temperature, ensuring that cellular functions and physiological processes can continue in cold environments. In the prevailing model of thermogenesis, when the hypothalamus senses cold temperatures it triggers sympathetic discharge, resulting in the release of noradrenaline in brown adipose tissue and white adipose tissue. Acting via the β(3)-adrenergic receptors, noradrenaline induces lipolysis in white adipocytes, whereas it stimulates the expression of thermogenic genes, such as PPAR-γ coactivator 1a (Ppargc1a), uncoupling protein 1 (Ucp1) and acyl-CoA synthetase long-chain family member 1 (Acsl1), in brown adipocytes. However, the precise nature of all the cell types involved in this efferent loop is not well established. Here we report in mice an unexpected requirement for the interleukin-4 (IL-4)-stimulated program of alternative macrophage activation in adaptive thermogenesis. Exposure to cold temperature rapidly promoted alternative activation of adipose tissue macrophages, which secrete catecholamines to induce thermogenic gene expression in brown adipose tissue and lipolysis in white adipose tissue. Absence of alternatively activated macrophages impaired metabolic adaptations to cold, whereas administration of IL-4 increased thermogenic gene expression, fatty acid mobilization and energy expenditure, all in a macrophage-dependent manner. Thus, we have discovered a role for alternatively activated macrophages in the orchestration of an important mammalian stress response, the response to cold.
Authors:
Khoa D Nguyen; Yifu Qiu; Xiaojin Cui; Y P Sharon Goh; Julia Mwangi; Tovo David; Lata Mukundan; Frank Brombacher; Richard M Locksley; Ajay Chawla
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-11-20
Journal Detail:
Title:  Nature     Volume:  480     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-01     Completed Date:  2012-02-23     Revised Date:  2012-04-05    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  104-8     Citation Subset:  IM    
Affiliation:
Immunology Program, Stanford University, Palo Alto, California 94305, USA.
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue / cytology,  metabolism
Animals
Body Temperature / genetics
Catecholamines / metabolism*
Cells, Cultured
Cold Temperature
Energy Metabolism
Gene Expression Regulation
Humans
Interleukin-4
Macrophage Activation*
Macrophages / metabolism,  physiology*
Male
Mice
Mice, Inbred BALB C
Stress, Physiological / physiology*
Thermogenesis / physiology*
U937 Cells
Grant Support
ID/Acronym/Agency:
DK076760/DK/NIDDK NIH HHS; DK094641/DK/NIDDK NIH HHS; DP1 OD006415-01/OD/NIH HHS; DP1 OD006415-02/OD/NIH HHS; DP1OD006415/OD/NIH HHS; HL07674/HL/NHLBI NIH HHS; R01 DK076760-04/DK/NIDDK NIH HHS; R01 DK076760-05/DK/NIDDK NIH HHS; R01 DK076760-06/DK/NIDDK NIH HHS; R01 DK081405-05/DK/NIDDK NIH HHS; R01 DK094641-01/DK/NIDDK NIH HHS; R01 HL076746-06A1/HL/NHLBI NIH HHS; R01 HL076746-08/HL/NHLBI NIH HHS; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Catecholamines; 207137-56-2/Interleukin-4
Comments/Corrections
Comment In:
Nature. 2011 Dec 1;480(7375):46-7   [PMID:  22101432 ]

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