In obesity, the skeletal muscle capillary network regresses and the insulin-mediated capillary recruitment is impaired. However, it has been shown that in the early stage of advanced obesity, an increased functional vascular response can partially compensate for other mechanisms of insulin resistance. The present study aimed to investigate the changes in the capillary network around individual muscle fibres during the early stage of obesity and insulin resistance in mice using 3D analysis. Capillaries and muscle fibres of the gluteus maximus muscles of seven high-fat-diet-induced obese and insulin-resistant mice and seven age-matched lean healthy mice were immunofluorescently labelled in thick transverse muscle sections. Stacks of images were acquired using confocal microscope. Capillary network characteristics were estimated by methods of quantitative image analysis. Muscle fibre typing was performed by histochemical analysis of myosin heavy chain isoforms on thin serial sections of skeletal muscle. Capillary length per muscle fibre length and capillary length per muscle fibre surface were increased by 27% and 23%, respectively, around small muscle fibres in obese mice, while there were no significant comparative differences around large fibres of obese and lean mice. Furthermore, the capillarization was larger around small compared to large fibres and there was a shift toward fast type myosin heavy chain isoforms, with no significant changes in muscle fibre diameters, tortuosity and anisotropy in obese mice. Overall, the results show that obese insulin-resistant mice have selective increase in capillarization around small predominantly intermediate muscle fibres, which is most likely related to the impaired glucose metabolism characteristic of type 2 diabetes.

中文翻译：

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肥胖胰岛素抵抗小鼠骨骼肌毛细血管网络的3D分析。

在肥胖症中，骨骼肌毛细血管网络消退，胰岛素介导的毛细血管募集受损。但是，已经表明，在晚期肥胖的早期，功能性血管反应的增强可以部分补偿胰岛素抵抗的其他机制。本研究旨在通过3D分析研究肥胖症早期阶段小鼠肌肉中单个肌纤维周围毛细血管网络的变化以及胰岛素抵抗。在厚厚的横肌切片中采用免疫荧光标记法对七只高脂饮食诱导的肥胖和胰岛素抵抗小鼠和七只年龄匹配的瘦弱健康小鼠的臀大肌的毛细血管和肌纤维进行了免疫荧光标记。使用共聚焦显微镜获取图像堆栈。通过定量图像分析的方法来估计毛细管网络的特征。肌纤维分型是通过对骨骼肌薄系列切片上的肌球蛋白重链同工型进行组织化学分析来进行的。在肥胖小鼠的小肌纤维周围，每条肌纤维长度的毛细管长度和每条肌纤维表面的毛细管长度分别增加27％和23％，而在肥胖和瘦小鼠的大纤维周围，则无显着的比较差异。此外，与大纤维相比，小纤维周围的毛细血管化更大，并且向快速型肌球蛋白重链同工型转变，肥胖小鼠的肌肉纤维直径，曲折性和各向异性没有显着变化。全面的，