Sarcopenia: investigation of metabolic changes and its associated mechanisms.

IF 5.3 2区医学 Q2 CELL BIOLOGY Skeletal Muscle Pub Date : 2023-01-19 DOI:10.1186/s13395-022-00312-w

Jair Marques, Engy Shokry, Olaf Uhl, Lisa Baber, Fabian Hofmeister, Stefanie Jarmusch, Martin Bidlingmaier, Uta Ferrari, Berthold Koletzko, Michael Drey

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引用次数: 2

Abstract

Background: Sarcopenia is one of the most predominant musculoskeletal diseases of the elderly, defined as age-related progressive and generalized loss of muscle mass with a simultaneous reduction in muscle strength and/or function. Using metabolomics, we aimed to examine the association between sarcopenia and the plasma metabolic profile of sarcopenic patients, measured using a targeted HPLC-MS/MS platform.

Methods: Plasma samples from 22 (17 men) hip fracture patients undergoing surgery (8 sarcopenic, age 81.4+6.3, and 14 non-sarcopenic, age 78.4±8.1) were analyzed. T test, fold change, orthogonal partial least squares discriminant analysis, and sparse partial least squares discriminant analysis were used for mining significant features. Metabolite set enrichment analysis and mediation analysis by PLSSEM were thereafter performed.

Results: Using a univariate analysis for sarcopenia z score, the amino acid citrulline was the only metabolite with a significant group difference after FDR correction. Positive trends were observed between the sarcopenia z score and very long-chain fatty acids as well as dicarboxylic acid carnitines. Multivariate analysis showed citrulline, non-esterified fatty acid 26:2, and decanedioyl carnitine as the top three metabolites according to the variable importance in projection using oPLS-DA and loadings weight by sPLS-DA. Metabolite set enrichment analysis showed carnitine palmitoyltransferase deficiency (II) as the highest condition related to the metabolome.

Conclusions: We observed a difference in the plasma metabolic profile in association with different measures of sarcopenia, which identifies very long-chain fatty acids, Carn.DC and citrulline as key variables associated with the disease severity. These findings point to a potential link between sarcopenia and mitochondrial dysfunction and portraits a number of possible biochemical pathways which might be involved in the disease pathogenesis.

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肌肉减少症:代谢变化及其相关机制的研究。

背景:肌少症是老年人最主要的肌肉骨骼疾病之一，定义为与年龄相关的进行性和全身性肌肉质量损失，同时肌肉力量和/或功能下降。利用代谢组学，我们旨在研究肌肉减少症与肌肉减少症患者血浆代谢谱之间的关系，使用靶向HPLC-MS/MS平台进行测量。方法:分析22例(男性17例)髋部骨折手术患者的血浆样本，其中肌肉减少症8例，年龄81.4±6.3岁，非肌肉减少症14例，年龄78.4±8.1岁。采用T检验、折叠变化、正交偏最小二乘判别分析和稀疏偏最小二乘判别分析挖掘显著特征。随后进行代谢物集富集分析和PLSSEM中介分析。结果:通过对肌肉减少症z评分的单变量分析，氨基酸瓜氨酸是FDR校正后唯一具有显著组差异的代谢物。骨骼肌减少症z值与长链脂肪酸和二羧酸肉毒碱呈正相关。多因素分析显示，根据oPLS-DA预测的变量重要性和sPLS-DA负荷重量，瓜氨酸、非酯化脂肪酸26:2和十二烷基肉碱是前三名代谢物。代谢组富集分析显示，肉碱棕榈酰转移酶缺陷(II)是与代谢组相关的最高条件。结论:我们观察到血浆代谢谱的差异与肌肉减少症的不同测量值有关，其中确定了非常长链脂肪酸，卡恩。DC和瓜氨酸是与疾病严重程度相关的关键变量。这些发现指出了肌少症和线粒体功能障碍之间的潜在联系，并描绘了一些可能参与疾病发病机制的生化途径。

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来源期刊

Skeletal Muscle CELL BIOLOGY-

CiteScore

9.10

自引率

0.00%

发文量

审稿时长

12 weeks

期刊介绍： The only open access journal in its field, Skeletal Muscle publishes novel, cutting-edge research and technological advancements that investigate the molecular mechanisms underlying the biology of skeletal muscle. Reflecting the breadth of research in this area, the journal welcomes manuscripts about the development, metabolism, the regulation of mass and function, aging, degeneration, dystrophy and regeneration of skeletal muscle, with an emphasis on understanding adult skeletal muscle, its maintenance, and its interactions with non-muscle cell types and regulatory modulators. Main areas of interest include: -differentiation of skeletal muscle- atrophy and hypertrophy of skeletal muscle- aging of skeletal muscle- regeneration and degeneration of skeletal muscle- biology of satellite and satellite-like cells- dystrophic degeneration of skeletal muscle- energy and glucose homeostasis in skeletal muscle- non-dystrophic genetic diseases of skeletal muscle, such as Spinal Muscular Atrophy and myopathies- maintenance of neuromuscular junctions- roles of ryanodine receptors and calcium signaling in skeletal muscle- roles of nuclear receptors in skeletal muscle- roles of GPCRs and GPCR signaling in skeletal muscle- other relevant aspects of skeletal muscle biology. In addition, articles on translational clinical studies that address molecular and cellular mechanisms of skeletal muscle will be published. Case reports are also encouraged for submission. Skeletal Muscle reflects the breadth of research on skeletal muscle and bridges gaps between diverse areas of science for example cardiac cell biology and neurobiology, which share common features with respect to cell differentiation, excitatory membranes, cell-cell communication, and maintenance. Suitable articles are model and mechanism-driven, and apply statistical principles where appropriate; purely descriptive studies are of lesser interest.