School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan.
Nutrition Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
Mediators Inflamm. 2020 Feb 13;2020:3153186. doi: 10.1155/2020/3153186. eCollection 2020.
This study investigated whether glutamine (GLN) pretreatment can enhance circulating endothelial progenitor cells (EPCs) and attenuate inflammatory reaction in high-fat diet-induced obese mice with limb ischemia. Mice were assigned to a normal control (NC), high-fat control (HC), limb ischemia (HI), and GLN limb ischemia (HG) groups. The NC group provided chow diet and treated as a negative control. Mice in the HC and HI groups were fed a high-fat diet which 60% energy provided by fat for 8 weeks. Mice in the HG group were fed the same diet for 4 weeks and then transferred to a high-fat diet with 25% of total protein nitrogen provided as GLN to replace part of the casein for the subsequent 4 weeks. After feeding 8 weeks, mice in the HC group were sham-operated, while the HI and HG groups underwent an operation to induce limb ischemia. All mice except the NC group were euthanized on either day 1 or 7 after the operation. The results showed that the 8 weeks' high-fat diet feeding resulted in obesity. The HG group had higher circulating EPCs on day 1 while muscle vascular endothelial growth factor, matrix metalloproteinase-9, and hypoxia-inducible factor-1 gene expressions were higher on day 7 postischemia than those of the HI group. The superoxide dismutase activity and reduced glutathione content in affected muscles were higher, whereas mRNA expressions of interleukin-6 and tumor necrosis factor- were lower in the HG than those in the HI group. These findings suggest that obese mice pretreated with GLN-supplemented high-fat diet increased circulating EPC percentage, enhanced the antioxidant capacity, and attenuated inflammatory reactions in response to limb ischemia.
本研究旨在探讨谷氨酰胺(GLN)预处理能否增强高脂饮食诱导的肥胖伴有肢体缺血的小鼠循环内皮祖细胞(EPC)并减轻炎症反应。将小鼠分为正常对照组(NC)、高脂对照组(HC)、肢体缺血组(HI)和 GLN 肢体缺血组(HG)。NC 组给予普通饮食作为阴性对照。HC 和 HI 组给予高脂饮食,其中 60%的能量来自脂肪,喂养 8 周。HG 组给予相同的饮食 4 周,然后用含有 25%总蛋白氮的 GLN 替代部分乳清蛋白,继续喂养 4 周。喂养 8 周后,HC 组假手术,HI 和 HG 组进行手术诱导肢体缺血。除 NC 组外,所有小鼠均于术后第 1 或第 7 天处死。结果显示,8 周高脂饮食喂养导致肥胖。HG 组在第 1 天的循环 EPC 更高,而在缺血后第 7 天,肌肉血管内皮生长因子、基质金属蛋白酶-9 和缺氧诱导因子-1 的基因表达更高。受影响肌肉中的超氧化物歧化酶活性和还原型谷胱甘肽含量较高,而 HG 组的白细胞介素-6 和肿瘤坏死因子-α的 mRNA 表达低于 HI 组。这些发现表明,高脂饮食预处理加 GLN 的肥胖小鼠增加了循环 EPC 比例,增强了抗氧化能力,并减轻了肢体缺血后的炎症反应。