Objective

A sustained high fat diet in mice mimics many features of human obesity. We used male and female Non-Swiss albino mice to investigate the impact of short and long-term high-fat diet-(HFD)-induced obesity on the peripheral neuromuscular junction (NMJ) and whether obesity-related synaptic structural alterations were reversible after switching obese mice from HFD to a standard fat diet (SD).

Methods

HFD-induced obese and age-matched control mice fed SD were used. We carried out in vivo time lapse imaging to monitor changes of synapses over time, quantitative fluorescence imaging to study the regulation of acetylcholine receptor number and density at neuromuscular junctions, and high resolution confocal microscope to study structural alterations in both the pre- and postsynaptic apparatus.

Results

Time-lapse imaging in vivo over a 9 month period revealed that NMJs of HFD obese male mice display a variety of obesity-related structural alterations, including the disappearance of large synaptic areas, significant reduction in the density/number of nicotinic acetylcholine receptor (AChRs), abnormal distribution of AChRs, high turnover rate of AChRs, retraction of axons from lost postsynaptic sites, and partially denervated synapses. The severity of these synaptic alterations is associated with the duration of obesity. However, no substantial alterations were observed at NMJs of age-matched HFD obese female mice or male mice fed with a standard or low fat diet. Intriguingly, when obese male mice were switched from HFD to a standard diet, receptor density and the abnormal pattern of AChR distribution were completely reversed to normal, whereas lost synaptic structures were not restored.

Conclusions

These results show that the obese male mice are more vulnerable than female mice to the impacts of long-term HFD on the NMJ damage and provide evidence that diet restriction can partially reverse obesity-related synaptic changes.

中文翻译：

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高脂饮食诱导的肥胖雄性小鼠中神经肌肉突触的拆卸。

目的

小鼠持续的高脂饮食模仿了人类肥胖的许多特征。我们使用雄性和雌性非瑞士白化病小鼠研究了短期和长期的高脂饮食（HFD）诱导的肥胖对周围神经肌肉接头（NMJ）的影响，以及肥胖相关的突触结构改变在之后是否可逆将肥胖小鼠从HFD转换为标准脂肪饮食（SD）。

方法

使用喂食SD的HFD诱导的肥胖和年龄匹配的对照小鼠。我们进行了体内时间推移成像以监测突触随时间的变化，定量荧光成像研究了神经肌肉接头处乙酰胆碱受体数量和密度的调节，高分辨率共聚焦显微镜研究了突触前和突触后装置的结构变化。

结果

历时9个月的体内延时成像显示，HFD肥胖雄性小鼠的NMJ表现出多种与肥胖有关的结构变化，包括大突触区域的消失，烟碱型乙酰胆碱受体（AChRs）的密度/数量显着降低。 ），AChR的异常分布，AChR的高周转率，轴突从丢失的突触后位点缩回以及部分神经突触消失。这些突触改变的严重程度与肥胖症的持续时间有关。但是，在年龄匹配的HFD肥胖雌性小鼠或饲喂标准或低脂饮食的雄性小鼠的NMJ处未观察到实质性改变。有趣的是，将肥胖的雄性小鼠从高脂饮食改为标准饮食后，受体密度和AChR分布异常模式完全恢复为正常，

结论

这些结果表明，肥胖的雄性小鼠比雌性小鼠更容易受到长期HFD对NMJ损害的影响，并提供饮食限制可以部分逆转肥胖相关的突触变化的证据。