Laboratory of Cellular and Molecular Biology, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene, Algiers, Algeria.
PLoS Negl Trop Dis. 2012;6(7):e1740. doi: 10.1371/journal.pntd.0001740. Epub 2012 Jul 17.
Scorpion venom induces systemic inflammation characterized by an increase in cytokine release and chemokine production. There have been few experimental studies assessing the effects of scorpion venom on adipose tissue function in vivo.
METHODOLOGY/PRINCIPAL FINDINGS: To study the adipose tissue inflammation (ATI) induced by Androctonus australis hector (Aah) venom and to assess possible mechanisms of ATI, mice (n = 6, aged 1 month) were injected with Aah (0.45 mg/kg), toxic fraction of Aah (FTox-G50; 0.2 mg/kg) or saline solution (control). Inflammatory responses were evaluated by ELISA and cell sorting analyses in adipose tissue 45 minutes and 24 hours after injection. Quantitative real-time PCR was used to assess the regulation of genes implicated in glucose uptake. The titers of selected inflammatory cytokines (IL-1β, IL-6 and TNF-α) were also determined in sera and in insulin target tissues. The serum concentration of IL-1β rose 45 minutes after envenomation and returned to basal level after 24 hours. The pathophysiological effects of the venom after 24 hours mainly involved M1-proinflammatory macrophage infiltration in adipose tissue combined with high titers of IL-1β, IL-6 and TNF-α. Indeed, TNF-α was strongly induced in both adipose tissue and skeletal muscle. We studied the effects of Aah venom on genes implicated in insulin-stimulated glucose uptake. Insulin induced a significant increase in the expression of the mRNAs for hexokinase 2 and phosphatidylinositol 3-kinase in both skeletal muscle and adipose tissue in control mice; this upregulation was completely abolished after 24 hours in mice envenomed with Aah or FTox-G50.
CONCLUSIONS/SIGNIFICANCE: Our findings suggest that Aah venom induces insulin resistance by mechanisms involving TNF-α-dependent Map4k4 kinase activation in the adipose tissue.
蝎子毒液会引起全身炎症，其特征是细胞因子释放和趋化因子产生增加。目前，关于蝎子毒液对体内脂肪组织功能影响的实验研究较少。
方法/主要发现：为了研究 Androctonus australis hector (Aah) 毒液引起的脂肪组织炎症 (ATI)，并评估 ATI 的可能机制，我们给 6 只 1 个月大的小鼠（n=6）注射 Aah（0.45 mg/kg）、Aah 的毒性部分（FTox-G50；0.2 mg/kg）或生理盐水溶液（对照组）。注射后 45 分钟和 24 小时，通过 ELISA 和细胞分选分析评估炎症反应。使用定量实时 PCR 评估与葡萄糖摄取相关基因的调控。还在血清和胰岛素靶组织中测定了选定的炎症细胞因子（IL-1β、IL-6 和 TNF-α）的滴度。毒液注射 45 分钟后血清中 IL-1β 水平升高，24 小时后恢复基础水平。24 小时后，毒液的病理生理作用主要涉及脂肪组织中 M1 促炎巨噬细胞浸润，以及高水平的 IL-1β、IL-6 和 TNF-α。事实上，TNF-α 在脂肪组织和骨骼肌中均强烈诱导。我们研究了 Aah 毒液对与胰岛素刺激的葡萄糖摄取相关基因的影响。在对照组小鼠中，胰岛素诱导骨骼肌和脂肪组织中己糖激酶 2和磷脂酰肌醇 3-激酶的 mRNA 表达显著增加；在 Aah 或 FToX-G50 中毒的小鼠中，这种上调在 24 小时后完全被阻断。
结论/意义：我们的研究结果表明，Aah 毒液通过 TNF-α 依赖的 Map4k4 激酶在脂肪组织中的激活，引起胰岛素抵抗。
