Neuropeptide FF increases M2 activation and self-renewal of adipose tissue macrophages
| Autor: | José T. Real, Stephan Paschke, Lajos Balogh, Jong-Seok Lim, E. Marion Schneider, Raphaëlle Quillet, Sorim Nam, Safia Ayachi, Frédéric Simonin, Tamás Röszer, Julianna Thuróczy, Grace Ampem, Jin-Chung Chen, Hind Azegrouz, Jacqueline A. Brinkman, Ivan C. Gerling, Ya Tin Lin, Anh Cuong Hoang, Syed F. Hassnain Waqas, Dudley W. Lamming, Juncal Martinez-Ibañez, Christine M. Seroogy |
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| Přispěvatelé: | Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS) |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty [SDV.BIO]Life Sciences [q-bio]/Biotechnology Ubiquitin-Protein Ligases Adipose tissue macrophages MafB Transcription Factor Adipose tissue Mice Transgenic Receptors Cell Surface Self renewal Mice 03 medical and health sciences Clinical investigation Internal medicine medicine Animals Neuropeptide FF Transcription factor Adaptor Proteins Signal Transducing Cell Proliferation STAT6 2. Zero hunger Arginase biology business.industry Chemistry Macrophages Proteins Sciences du Vivant [q-bio]/Biotechnologies General Medicine Macrophage Activation Interleukin-10 Ubiquitin ligase Cell biology Endocrinology 030104 developmental biology Adipose Tissue MAFB biology.protein Interleukin-4 Corrigendum business Oligopeptides Macrophage proliferation Research Article |
| Zdroj: | JOURNAL OF CLINICAL INVESTIGATION r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA instname Journal of Clinical Investigation Journal of Clinical Investigation, American Society for Clinical Investigation, 2017, 127 (7), pp.2842-2854. ⟨10.1172/JCI90152⟩ |
| ISSN: | 1558-8238 0021-9738 |
| Popis: | The quantity and activation state of adipose tissue macrophages (ATMs) impact the development of obesity-induced metabolic diseases. Appetite-controlling hormones play key roles in obesity; however, our understanding of their effects on ATMs is limited. Here, we have shown that human and mouse ATMs express NPFFR2, a receptor for the appetite-reducing neuropeptide FF (NPFF), and that NPFFR2 expression is upregulated by IL-4, an M2-polarizing cytokine. Plasma levels of NPFF decreased in obese patients and high-fat diet-fed mice and increased following caloric restriction. NPFF promoted M2 activation and increased the proliferation of murine and human ATMs. Both M2 activation and increased ATM proliferation were abolished in NPFFR2-deficient ATMs. Mechanistically, the effects of NPFF involved the suppression of E3 ubiquitin ligase RNF128 expression, resulting in enhanced stability of phosphorylated STAT6 and increased transcription of the M2 macrophage-associated genes IL-4 receptor α (Il4ra), arginase 1 (Arg1), IL-10 (Il10), and alkylglycerol monooxygenase (Agmo). NPFF induced ATM proliferation concomitantly with the increase in N-Myc downstream-regulated gene 2 (Ndrg2) expression and suppressed the transcription of Ifi200 cell-cycle inhibitor family members and MAF bZIP transcription factor B (Mafb), a negative regulator of macrophage proliferation. NPFF thus plays an important role in supporting healthy adipose tissue via the maintenance of metabolically beneficial ATMs. |
| Databáze: | OpenAIRE |
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