Spexin (SPX) is a novel adipokine related to many metabolic effects, such as gastrointestinal movements, insulin and glucose homeostasis, lipid metabolism and energy balance. This study evaluates the role of SPX in the improvement of the metabolic and inflammatory profile in fructose-rich-diet obese mice. Adult Swiss mice were supplemented or not with fructose (20% in tap water, FRD and CTR, respectively) for 10 weeks. The last ten days, mice were treated or not with SPX (ip. 29 μg/Kg/day, FRD-SPX and CTR-SPX, respectively). A positive correlation was observed between body weight prior to treatment and weight loss after SPX challenge. Moreover, plasma and liver triglycerides and adipose tissue (AT) features (mass, adipocyte hypertrophy, mRNA of leptin) were improved. SPX also induced a reduction in epididymal AT (EAT) expression of TNFα, IL1β and IL6 and an improvement in IL10 and CD206. M1 macrophages in EAT, principally the Ly6C- populations (M1a and M1b), were decreased. Adipocytes from FRD-SPX mice induced less macrophage activation (IL6, mRNA and secretion) than FRD after overnight co-culture with the monocyte cell line (RAW264.7) in stimulated conditions (M1 activation, LPS 100 ng/mL). Finally, in vitro, monocytes pre-incubated with SPX and stimulated with LPS showed decreased inflammatory mRNA markers compared to monocytes with LPS alone. In conclusion, SPX decreased body weight and improved the metabolic profile and adipocyte hypertrophy. Inflammatory Ly6C- macrophages decreased, together with inflammatory marker expression. In vitro studies demonstrate that SPX induced a decrease in M1 macrophage polarization directly or through mature adipocytes.

中文翻译：

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“ Spexin改善肥胖小鼠的脂肪组织炎症和巨噬细胞募集”。

Spexin（SPX）是一种新型的脂肪因子，与许多代谢作用有关，例如胃肠道运动，胰岛素和葡萄糖体内稳态，脂质代谢和能量平衡。这项研究评估了SPX在富含果糖饮食的肥胖小鼠中代谢和炎症状况改善中的作用。给成年瑞士小鼠补充或不补充果糖（分别在自来水中20％，FRD和CTR）10周。在最后十天，对小鼠进行SPX处理（不使用，分别为29μg/ Kg /天，FRD-SPX和CTR-SPX）。在治疗之前的体重与SPX激发后的体重减轻之间观察到正相关。此外，血浆和肝甘油三酸酯和脂肪组织（AT）的功能（质量，脂肪细胞肥大，瘦素的mRNA）得到改善。SPX还诱导了附睾AT（EAT）TNFα表达的降低，IL1β和IL6以及IL10和CD206的改善。EAT中的M1巨噬细胞减少，主要是Ly6C-种群（M1a和M1b）减少。在刺激条件下（M1激活，LPS 100 ng / mL）与单核细胞系（RAW264.7）共培养过夜后，来自FRD-SPX小鼠的脂肪细胞诱导的巨噬细胞活化（IL6，mRNA和分泌）比FRD少。最后，在体外，与单独使用LPS的单核细胞相比，用SPX预孵育并用LPS刺激的单核细胞显示出降低的炎症mRNA标记。总之，SPX减轻了体重，改善了代谢状况和脂肪细胞肥大。炎性Ly6C-巨噬细胞减少，并伴有炎性标志物表达。体外研究表明，SPX直接或通过成熟的脂肪细胞诱导M1巨噬细胞极化的降低。