Anti-inflammatory effects of exercise training in adipose tissue do not require FGF21.
Anti-inflammatory effects of exercise training in adipose tissue do not require FGF21.
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DOI：
10.1530/joe-17-0190
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发表时间：
2017-11
期刊：
影响因子：
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通讯作者：
Vieira-Potter VJ
中科院分区：
文献类型：
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作者：
Porter JW;Rowles JL 3rd;Fletcher JA;Zidon TM;Winn NC;McCabe LT;Park YM;Perfield JW 2nd;Thyfault JP;Rector RS;Padilla J;Vieira-Potter VJ
运动增强胰岛素敏感性;它还通过不明确的机制改善脂肪细胞代谢并减少脂肪组织炎症。成纤维细胞生长因子21（FGF 21）是一种多效的胰岛素样蛋白，其胰岛素增敏特性主要通过脂肪组织（AT）中的受体信号传导介导。最近，FGF 21也被证明具有抗炎特性。与此同时，在一些但不是所有的研究中报道了运动和循环中FGF 21水平增加之间的关联。因此，FGF 21在AT中介导运动的积极代谢作用的作用尚不清楚。在这项研究中，使用FGF 21敲除（KO）小鼠直接评估FGF 21在介导运动对白色AT（WAT）和棕色AT（BAT）的代谢和抗炎作用中的作用。给雄性FGF 21 KO和野生型小鼠提供跑步轮或保持久坐8周（n=9-15/组），并比较肥胖、胰岛素敏感性（即，HOMA-IR、Adipo-IR）和AT炎症和代谢功能（例如，线粒体酶活性、亚基含量）。FGF 21 KO小鼠的肥胖和Adipo-IR增加，EX降低。FGF 21 KO动物的BAT具有降低的线粒体含量和降低的相对质量，两者均通过EX标准化。WAT和BAT炎症在FGF 21 KO小鼠中升高，在两种基因型中通过EX. EX增加WT小鼠的WAT Pgc 1 α基因表达、柠檬酸合酶活性、考克斯I含量和总AMPK含量，但不增加FGF 21 KO小鼠。总的来说，这些发现揭示了FGF 21在WAT和BAT中的先前未被重视的抗炎作用，但不支持FGF 21对于EX介导的抗炎作用是必需的。
Exercise enhances insulin sensitivity; it also improves adipocyte metabolism and reduces adipose tissue inflammation through poorly-defined mechanisms. Fibroblast growth factor 21 (FGF21) is a pleiotropic hormone-like protein whose insulin-sensitizing properties are predominantly mediated via receptor signaling in adipose tissue (AT). Recently, FGF21 has also been demonstrated to have anti-inflammatory properties. Meanwhile, an association between exercise and increased circulating FGF21 levels has been reported in some, but not all studies. Thus, the role that FGF21 plays in mediating the positive metabolic effects of exercise in AT are unclear. In this study, FGF21 knock-out (KO) mice were used to directly assess the role of FGF21 in mediating the metabolic and anti-inflammatory effects of exercise on white AT (WAT) and brown AT (BAT). Male FGF21KO and wild-type mice were provided running wheels or remained sedentary for 8 weeks (n=9–15/group) and compared for adiposity, insulin sensitivity (i.e., HOMA-IR, Adipo-IR), and AT inflammation and metabolic function (e.g., mitochondrial enzyme activity, subunit content). Adiposity and Adipo-IR were increased in FGF21KO mice and decreased by EX. The BAT of FGF21KO animals had reduced mitochondrial content and decreased relative mass, both normalized by EX. WAT and BAT inflammation was elevated in FGF21KO mice, reduced in both genotypes by EX. EX increased WAT Pgc1alpha gene expression, citrate synthase activity, COX I content, and total AMPK content in WT but not FGF21KO mice. Collectively, these findings reveal a previously unappreciated anti-inflammatory role for FGF21 in WAT and BAT, but do not support that FGF21 is necessary for EX-mediated anti-inflammatory effects.