AIM Critical limb ischaemia (CLI) is characterized by inadequate angiogenesis, arteriolar remodelling and chronic myopathy, which are most severe in type 2 diabetic patients. Hypertriglyceridaemia, commonly observed in these patients, compromises macrovascular function. However, the effects of high-fat diet-induced increases in circulating lipids on microvascular remodelling are not established. Here, we investigated if high-fat diet would mimic the detrimental effect of type 2 diabetes on post-ischaemia vascular remodelling and muscle regeneration, using a mouse model of hindlimb ischaemia. METHODS Male C57Bl6/J mice were fed with normal or high-fat diets for 8 weeks prior to unilateral femoral artery ligation. Laser doppler imaging was used to assess limb perfusion recovery. Vascular recovery, inflammation, myofibre regeneration and fibrosis were assessed at 4 or 14 days post-ligation by histology and RNA analyses. Capillary-level haemodynamics were assessed by intravital microscopy of control and regenerating muscles 14 days post-ligation. RESULTS High-fat diet increased muscle succinate dehydrogenase activity and capillary-level oxygen supply. At 4 days post-ligation, no diet differences were detected in muscle damage, inflammatory infiltration or capillary activation. At 14 days post-ligation, high fat-fed mice displayed accelerated limb blood flow recovery, elevated capillary and arteriole densities as well as greater red blood cell supply rates and capillary-level oxygen supply. Regenerating muscles from high fat-fed mice displayed lower interstitial fat and collagen deposition. CONCLUSION The muscle-level adaptations to high-fat diet improved multiple aspects of muscle recovery in response to ischaemia and did not recapitulate the worse outcomes seen in diabetic CLI patients.

中文翻译：

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高脂饮食预处理可改善缺血小鼠骨骼肌再生过程中的微血管重塑。

目的严重肢体缺血（CLI）的特征是血管生成不足，小动脉重构和慢性肌病，这在2型糖尿病患者中最为严重。在这些患者中常见的高甘油三酸酯血症会损害大血管功能。然而，高脂饮食诱导循环脂质增加对微血管重塑的影响尚未建立。在这里，我们使用后肢缺血小鼠模型研究了高脂饮食是否能模拟2型糖尿病对缺血后血管重塑和肌肉再生的有害影响。方法在单侧股动脉结扎之前，先给雄性C57B16 / J小鼠喂食正常或高脂饮食8周。激光多普勒成像用于评估肢体灌注恢复。血管恢复，发炎，结扎后4或14天通过组织学和RNA分析评估肌纤维再生和纤维化。结扎后14天，通过活体显微镜检查对照组和再生肌的毛细血管水平血流动力学。结果高脂饮食可增加肌肉琥珀酸脱氢酶活性和毛细管水平的氧气供应。结扎后第4天，在肌肉损伤，炎症浸润或毛细血管活化方面未发现饮食差异。结扎后14天，高脂喂养的小鼠显示出加速的肢体血流恢复，升高的毛细血管和小动脉密度，以及更高的红细胞供应率和毛细管水平的氧气供应。高脂喂养小鼠的再生肌肉显示出较低的间质脂肪和胶原蛋白沉积。