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Metabolomics studies on db/db diabetic mice in skeletal muscle reveal effective clearance of overloaded intermediates by exercise
Analytica Chimica Acta ( IF 5.7 ) Pub Date : 2018-12-01 , DOI: 10.1016/j.aca.2017.11.082
Li Xiang , Hongsong Zhang , Juntong Wei , Xiao Yu Tian , Hemi Luan , Shangfu Li , Hongzhi Zhao , Guodong Cao , Arthur C.K. Chung , Chunxue Yang , Yu Huang , Zongwei Cai

Type 2 diabetes mellitus (T2DM) is characterized by hyperinsulinemia, hyperglycemia and insulin resistance, which correlated with high mortality worldwide. Exercise is one of the effective lifestyle interventions in maintaining blood glucose level in the normal range and lowering risk factors. Metabolomics approaches are powerful tools in systematic study of overall metabolic changes in response to disease or interventions. In this study, mass spectrometry-based metabolomics studies were performed to investigate the regulatory effect of moderate intensity of exercise on db/db diabetic mice in skeletal muscle. Both liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) have been carried out to monitor a wide range of regulated metabolites. Ninety-five metabolites were identified which contributing to the discrimination of db/m + control and db/db diabetic mice. The regulatory effects of exercise on these metabolites were mainly focusing on attenuating the levels of long-chain fatty acids (C14 to C18) and medium-to long-chain acylcarnitines (C12 to C18), indicated that exercise might play a positive role in inhibiting the accumulation of excessive lipids, which is positively related to insulin resistance. In addition, uric acid, which is a risk factor for inflammation, cardiovascular complications, and fatty liver in diabetic patients, together with its intermediates (such as inosinic acid, hypoxanthine, etc.) in purine metabolism pathway, were also substantially down regulated after exercise, indicating exercise might also be protective against hyperuricemia related risks in T2DM. These findings reveal that moderate intensity of exercise might play a positive role in improving the efficiency of lipid metabolism in skeletal muscle and meanwhile enhancing uric acid clearance to prevent lipid accumulation, which might contribute to improved body fitness and body muscle composition.

中文翻译:

骨骼肌中 db/db 糖尿病小鼠的代谢组学研究表明,运动可有效清除超负荷的中间体

2 型糖尿病 (T2DM) 的特征是高胰岛素血症、高血糖症和胰岛素抵抗,这与世界范围内的高死亡率相关。运动是将血糖水平维持在正常范围内并降低危险因素的有效生活方式干预措施之一。代谢组学方法是系统研究响应疾病或干预的整体代谢变化的有力工具。在这项研究中,进行了基于质谱的代谢组学研究,以研究中等强度运动对 db/db 糖尿病小鼠骨骼肌的调节作用。液相色谱-质谱联用 (LC-MS) 和气相色谱-质谱联用 (GC-MS) 已用于监测各种受管制的代谢物。鉴定了 95 种代谢物,它们有助于区分 db/m + 对照和 db/db 糖尿病小鼠。运动对这些代谢物的调节作用主要集中在降低长链脂肪酸(C14 至 C18)和中长链酰基肉碱(C12 至 C18)的水平,表明运动可能在抑制过多的脂质积累,与胰岛素抵抗呈正相关。此外,作为糖尿病患者炎症、心血管并发症和脂肪肝的危险因素的尿酸及其在嘌呤代谢途径中的中间体(如肌苷酸、次黄嘌呤等)也显着下调。运动,表明运动也可能对 T2DM 中与高尿酸血症相关的风险有保护作用。
更新日期:2018-12-01
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