IL-25 stimulates M2 macrophage polarization and thereby promotes mitochondrial respiratory capacity and lipolysis in adipose tissues against obesity.
IL-25 stimulates M2 macrophage polarization and thereby promotes mitochondrial respiratory capacity and lipolysis in adipose tissues against obesity.
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IL-25 刺激 M2 巨噬细胞极化，从而促进线粒体呼吸能力和脂肪组织中的脂肪分解，对抗肥胖
DOI：
10.1038/cmi.2016.71
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发表时间：
2018-05
影响因子：
24.1
通讯作者：
Yang Z
中科院分区：
文献类型：
--
作者：
Feng J;Li L;Ou Z;Li Q;Gong B;Zhao Z;Qi W;Zhou T;Zhong J;Cai W;Yang X;Zhao A;Gao G;Yang Z
肥胖和相关代谢疾病的特征是慢性低度炎症状态，伴有许多炎症细胞，特别是巨噬细胞的浸润。免疫分子，包括一些细胞因子，与新陈代谢有着密切的关系。白细胞介素（IL）-25是IL-17细胞因子家族的成员，可以调节巨噬细胞并缓解一些代谢功能障碍；然而，其在脂质代谢中的作用和机制仍有待广泛阐明。使用人血清和肝活检标本、高脂饮食诱导的肥胖小鼠和 DB/DB (Lepr−/−) 动物模型来检测肥胖和非酒精性脂肪肝疾病 (NAFLD) 中 IL-25 的表达。为了观察IL-25在脂质代谢中的作用，模型小鼠被给予IL-25或在体内过继转移IL-25教育的巨噬细胞，而骨髓来源的巨噬细胞，即巨噬细胞系RAW264。 7和从3T3-L1分化的脂肪细胞在体外使用。 NAFLD 患者和肥胖小鼠中 IL-25 降低。此外，IL-25 减少体重增加和脂质积累，增强巨噬细胞的脂质摄取，并通过交替激活巨噬细胞增加脂肪分解酶和 β-氧化酶的表达。 IL-25 还促进与 IL-25 训练的巨噬细胞共培养的脂肪细胞中的脂肪分解并抑制脂肪生成。此外，IL-25提高了线粒体呼吸能力和巨噬细胞的耗氧率，并产生更多的NAD+/NADH和ATP。总之，IL-25 可以刺激 M2 巨噬细胞极化，从而促进脂肪分解和线粒体呼吸能力，凸显了 IL-25 作为肥胖和相关代谢综合征治疗剂的潜力。
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.
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影响因子：
7.7
作者：
Cani, Patrice D.;Amar, Jacques;Burcelin, Remy
通讯作者：
Burcelin, Remy
DOI：
10.4049/jimmunol.1301176
发表时间：
2013-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hams E;Locksley RM;McKenzie AN;Fallon PG
通讯作者：
Fallon PG
影响因子：
7.7
作者：
Eljaafari, Assia;Robert, Maud;Pirola, Luciano
通讯作者：
Pirola, Luciano
影响因子：
6.9
作者：
Ahima, Rexford S.
通讯作者：
Ahima, Rexford S.
影响因子：
29.4
作者：
Chalasani, Naga;Younossi, Zobair;Sanyal, Arun J.
通讯作者：
Sanyal, Arun J.