Metabolomic profiling reveals severe skeletal muscle group-specific perturbations of metabolism in aged FBN rats
Metabolomic profiling reveals severe skeletal muscle group-specific perturbations of metabolism in aged FBN rats
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DOI：
10.1007/s10522-014-9492-5
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发表时间：
2014-06-01
期刊：
影响因子：
4.5
通讯作者：
Edens, Neile K.
中科院分区：
文献类型：
--
作者：
Garvey, Sean M.;Dugle, Janis E.;Edens, Neile K.
哺乳动物骨骼肌表现出与年龄相关的适应性和病理重塑。特别是有几块肌肉的进行性萎缩和退化超过了中位寿命。为了更好地了解心肌细胞对衰老的反应，我们使用半定量的全球代谢组学图谱来表征15个月大的成年大鼠和32个月大的老年Fischer 344 x Brown挪威(FBN)雄性大鼠之间的代谢变化趋势。FBN大鼠的腓肠肌表现出与年龄相关的萎缩，而比目鱼肌，直到32个月，表现出明显较少的萎缩迹象。分析腓肠肌和比目鱼肌，以及血浆和尿液。与成年腓肠肌相比，老年腓肠肌表现出糖酵解代谢降低的证据，包括糖酵解、糖原分解和磷酸戊糖途径中间产物的积累。丙酮酸随年龄增长而升高，而柠檬酸和烟酰胺腺嘌呤二核苷酸水平降低，这与线粒体异常一致。3-甲基组氨酸和游离氨基酸在老年腓肠肌中升高，表明肌肉萎缩。单不饱和脂肪酸油酸、顺式疫苗酸和棕榈油酸在老年腓肠肌中也增加，这表明脂肪代谢发生了变化。与腓肠肌相比，老年比目鱼肌在碳水化合物代谢方面的变化要小得多，但确实显示出几种糖酵解中间产物富马酸、苹果酸和黄素腺嘌呤二核苷酸的减少。与年龄增长相关的血浆生物化学物质包括甘胆酸盐、血红素、1，5-脱水葡萄糖醇、1-棕榈油酰甘油磷胆碱、棕榈油酸酯和肌酸。这些变化表明老年FBN大鼠的胰岛素敏感性降低。总之，这些数据突出了骨骼肌组特有的糖脂代谢紊乱，与老年FBN大鼠的线粒体功能障碍一致。
Mammalian skeletal muscles exhibit age-related adaptive and pathological remodeling. Several muscles in particular undergo progressive atrophy and degeneration beyond median lifespan. To better understand myocellular responses to aging, we used semi-quantitative global metabolomic profiling to characterize trends in metabolic changes between 15-month-old adult and 32-month-old aged Fischer 344 x Brown Norway (FBN) male rats. The FBN rat gastrocnemius muscle exhibits age-dependent atrophy, whereas the soleus muscle, up until 32 months, exhibits markedly fewer signs of atrophy. Both gastrocnemius and soleus muscles were analyzed, as well as plasma and urine. Compared to adult gastrocnemius, aged gastrocnemius showed evidence of reduced glycolytic metabolism, including accumulation of glycolytic, glycogenolytic, and pentose phosphate pathway intermediates. Pyruvate was elevated with age, yet levels of citrate and nicotinamide adenine dinucleotide were reduced, consistent with mitochondrial abnormalities. Indicative of muscle atrophy, 3-methylhistidine and free amino acids were elevated in aged gastrocnemius. The monounsaturated fatty acids oleate, cis-vaccenate, and palmitoleate also increased in aged gastrocnemius, suggesting altered lipid metabolism. Compared to gastrocnemius, aged soleus exhibited far fewer changes in carbohydrate metabolism, but did show reductions in several glycolytic intermediates, fumarate, malate, and flavin adenine dinucleotide. Plasma biochemicals showing the largest age-related increases included glycocholate, heme, 1,5-anhydroglucitol, 1-palmitoleoyl-glycerophosphocholine, palmitoleate, and creatine. These changes suggest reduced insulin sensitivity in aged FBN rats. Altogether, these data highlight skeletal muscle group-specific perturbations of glucose and lipid metabolism consistent with mitochondrial dysfunction in aged FBN rats.