IL-25 stimulates M2 macrophage polarization and thereby promotes mitochondrial respiratory capacity and lipolysis in adipose tissues against obesity
JournalCellular and Molecular Immunology
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AbstractObesity and associated metabolic diseases are characterized by a chronic low-grade inflammatory state with the infiltration of many inflammatory cells, especially macrophages. Immune molecules, including some cytokines, have a close relationship with metabolism. Interleukin (IL)-25 is a member of the IL-17 cytokine family that can regulate macrophages and alleviate some metabolic dysfunction; however, its role and mechanisms in lipid metabolism remain to be extensively clarified. Human serum and liver biopsy specimens, high-fat diet-induced obesity mice and DB/DB (Lepr?/?) animal models were used to examine IL-25 expression in obesity and nonalcoholic fatty liver diseases (NAFLD). To observe the role of IL-25 in lipid metabolism, model mice were administered with IL-25 or adoptively transferred with IL-25-educated macrophages in vivo, whereas bone marrow-derived macrophages, the macrophage cell line RAW264.7 and adipocytes differentiated from 3T3-L1 were used in vitro. IL-25 was decreased in NAFLD patients and obese mice. In addition, IL-25 reduced body weight gain and lipid accumulation, enhanced lipid uptake by macrophages and increased the expression of lipolysis and ?-oxidation enzymes via alternatively activating macrophages. IL-25 also promoted lipolysis and suppressed lipogenesis in adipocytes co-cultured with the IL-25-educated macrophages. Furthermore, IL-25 improved the mitochondrial respiratory capacity and oxygen consumption rate of macrophages and produced more NAD + /NADH and ATP. In conclusion, IL-25 can stimulate M2 macrophage polarization and thereby promote lipolysis and mitochondrial respiratory capacity, highlighting the potential for IL-25 to be used as a therapeutic agent against obesity and associated metabolic syndromes. Copyright 2017, CSI and USTC.
SponsorsThis study was supported by the National Nature Science Foundation of China: 81272338, 81272515, 81370945, 81471033, 81570871, 81570764 and 81600641; the National Key Sci-Tech Special Project of China: 2013ZX09102-053, 2015GKS-355; the Program for Doctoral Station in University: 20130171110053; the Key Project of the Nature Science Foundation of Guangdong Province, China: 2015A030311043, 2016A030311035; the Guangdong Natural Science Fund: 2014A020 212023, 2014A030313073, 2015A030313103 and 2015A030313029; the Guandong Science and Technology Project (2014A020212023, 2015B0 90903063 and 2016A020214001); the Guangzhou Science and Technology Project: 2014J4100162, 201508020033 and 201510010052; the Pearl River Nova Program of Guangzhou Municipality, China, Grant Number: 201610010186; the Chang jiang Scholars and Innovative Research Team in University: 985 project PCSIRT 0947; and the Fundamental Research Funds for the Central Universities of China (Youth Program 13ykpy06, 16ykpy24 and 31610046).
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85050993403&doi=10.1038%2fcmi.2016.71&partnerID=40&md5=55da1ac723198f59a4bd070803c338ab; http://hdl.handle.net/10713/9651