title: IL-25 stimulates M2 macrophage polarization and thereby promotes mitochondrial respiratory capacity and lipolysis in adipose tissues against obesity.
abstract: Obesity 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 β-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.
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Feng
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Lingyi
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Pediatrics, Affiliated Guangzhou Women and Children's Medical Center, Sun Yat-sen University, 510623, Guangzhou, China.
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Ou
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Li
authors.affiliation: Guangdong Provincial Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, 510063, Guangzhou, China.
authors.forename: Baoyong
authors.initials: B
authors.lastname: Gong
authors.affiliation: Pancreato-Biliary Surgery, First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, China.
authors.forename: Zhenxian
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Qi
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Ti
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Guangdong Engineering and Technology Research Center for Disease-Model Animals, SUN Yat-sen University, 510006, Guangzhou, China.
authors.forename: Weibin
authors.initials: W
authors.lastname: Cai
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, Department of Medicine, University of Maryland School of Medicine, 21201, Baltimore, MD, USA.
authors.forename: Aiping
authors.initials: A
authors.lastname: Zhao
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. gaogq@mail.sysu.edu.cn.
authors.forename: Guoquan
authors.initials: G
authors.lastname: Gao
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. yangzhh@mail.sysu.edu.cn.
authors.forename: Zhonghan
authors.initials: Z
authors.lastname: Yang
mesh_terms: D041721:3T3-L1 Cells; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000273:Adipose Tissue / Q000473:pathology*; D052436:Adipose Tissue, White / Q000187:drug effects / Q000473:pathology; D000818:Animals; D015992:Body Mass Index; D016764:Cell Polarity / Q000187:drug effects*; D019069:Cell Respiration / Q000187:drug effects; D004435:Eating; D006801:Humans; D020381:Interleukin-17 / Q000008:administration & dosage / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D009243:NAD / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000473:pathology; D009765:Obesity / Q000473:pathology*; D010101:Oxygen Consumption / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
chemical_list: D020381:Interleukin-17; D012333:RNA, Messenger; D009243:NAD; D000255:Adenosine Triphosphate
keywords: IL-25; adipocyte; immunometabolism; macrophage; obesity