Laboratorio de Neuroendocrinología, Instituto Multidisciplinario de Biología Celular (IMBICE, CICPBA-CONICET-UNLP), Calle 526, 10 y 11, La Plata 1900, Argentina; Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 1900, Argentina.
Laboratorio de Neuroendocrinología, Instituto Multidisciplinario de Biología Celular (IMBICE, CICPBA-CONICET-UNLP), Calle 526, 10 y 11, La Plata 1900, Argentina.
Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Jul;1865(7):158700. doi: 10.1016/j.bbalip.2020.158700. Epub 2020 Mar 19.
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.
Spexin (SPX) 是一种与许多代谢效应相关的新型脂肪因子，如胃肠运动、胰岛素和葡萄糖稳态、脂代谢和能量平衡。本研究评估了 SPX 在改善富含果糖饮食肥胖小鼠代谢和炎症特征中的作用。成年瑞士小鼠分别补充或不补充果糖（分别为自来水 20%的 FRD 和 CTR）10 周。最后十天，用或不用 SPX 处理小鼠（ip. 29 μg/Kg/天，分别为 FRD-SPX 和 CTR-SPX）。在治疗前的体重与 SPX 挑战后的体重减轻之间观察到正相关。此外，血浆和肝脏甘油三酯和脂肪组织（AT）特征（质量、脂肪细胞肥大、瘦素 mRNA）得到改善。SPX 还诱导附睾脂肪组织（EAT）TNFα、IL1β 和 IL6 的表达减少和 IL10 和 CD206 的改善。EAT 中的 M1 巨噬细胞，主要是 Ly6C 群体（M1a 和 M1b）减少。在刺激条件下（M1 激活，LPS 100ng/mL），与单核细胞系（RAW264.7）过夜共培养后，FRD-SPX 小鼠的脂肪细胞诱导的巨噬细胞激活（IL6，mRNA 和分泌）少于 FRD。最后，在体外，与单独 LPS 相比，用 SPX 预孵育并用 LPS 刺激的单核细胞显示出炎症 mRNA 标志物减少。总之，SPX 降低了体重，改善了代谢特征和脂肪细胞肥大。炎症 Ly6C 巨噬细胞减少，同时炎症标志物表达减少。体外研究表明，SPX 直接或通过成熟脂肪细胞诱导 M1 巨噬细胞极化减少。
