饮用水中添加脂多糖对小鼠能量代谢及行为的影响

摘要

[目的]研究长期饮水添加不同细菌来源脂多糖对小鼠采食、能量代谢以及行为变化的影响.[方法]选用48只5周龄C57/BL小鼠,随机分为8组,腹腔注射不同浓度脂多糖,观察采食量.进一步选用24只5周龄C57/BL小鼠,随机分为3组,分别饮用水中添加5μg·mL–1大肠埃希菌Escherichia coil O128:B12脂多糖组、5μg·mL–1大肠埃希菌O55:B5脂多糖组和不添加的对照组,试验周期为12周.试验结束前采用旷场和高空十字迷宫分析小鼠的运动和焦虑行为.试验结束后测定体组成,并采集皮下脂肪和脑核团样本分析相关基因表达.[结果]腹腔注射高剂量脂多糖抑制了小鼠采食,而饮用水中添加5μg·mL–1不同细菌脂多糖均显著提高了小鼠采食量(P<0.05),且к调了下丘脑弓状核中AgRP的mRNA表达量,而对POMC的mRNA的表达量无影响;饮用水中添加5μg·mL–1不同细菌脂多糖显著降低了小鼠饲料利用率和体脂沉积水平,同时显著促进了褐色脂肪UCP-1和PGC-1ɑ 的表达;饮用水中添加5μg·mL–1脂多糖对小鼠焦虑行为无影响,但显著促进了小鼠的自发运动.脂多糖显著促进了海马体中c-fos和DRD2 mRNA的表达.[结论]饮用水中添加大肠埃希菌脂多糖能提高小鼠食欲、促进脂肪代谢和自主运动,这可能与海马体多巴胺神经元系统活性增强有关.%[Objective]To investigate the effects of long-term drinking water supplemented with lipopolysaccharide (LPS) on feeding, energy metabolism and behavior of mice.[Method]Totally 48 five-week-old C57/BL mice were randomly divided into eight groups. Different concentrations of LPS were injected intraperitoneally to test food intake. Meanwhile, 24 five-week-old C57/BL mice were randomly divided into three groups including control group without LPS, O128:B12 group (adding 5 μg·mL–1 Escherichia coil O128:B12 LPS to drinking water) and O55:B5 group (adding 5 μg·mL–1 E. coil O55:B5 LPS to drinking water). The experiment period was 12 weeks. Open field test and elevated plus-maze test were used to analyze the movement and anxiety behavior of mice. At the end of experiment, the body composition was tested and samples of fat tissue and brain nucleus were collected for gene expression analysis.[Result]Intraperitoneal injection of high dose LPS inhibited food intake of mice. Adding 5 μg·mL–1 LPS from different bacteria to drinking water significantly increased food intake of mice (P<0.05), and upregulated AgRP mRNA expression in the hypothalamic arcuate nucleus, while POMC mRNA expression was not affected. Drinking LPS significantly reduced feed efficiency, decreased fat deposition, and promoted the expression of UCP-1 and PGC-1ɑ in brown fat. Drinking LPS did not influence mouse anxiety behavior, but significantly promoted the locomotor activity of mice. Drinking LPS also significantly upregulated mRNA expression of c-fos and DRD2 in hippocampus.[Conclusion]Adding E. coli LPS to drinking water could improve mouse appetite, promote adipose metabolism of mice and increase locomotor activity of mice, which might be related to the increased activity of dopamine neurons in the hippocampus.