Sarcopenia: investigation of metabolic changes and its associated mechanisms

Skeletal Muscle

Research

Michael Drey¹  Martin Bidlingmaier¹  Uta Ferrari¹  Lisa Baber¹  Fabian Hofmeister¹  Stefanie Jarmusch¹  Engy Shokry²  Olaf Uhl²  Jair Marques²  Berthold Koletzko² 

[1] Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany;Department of Paediatrics, LMU - Ludwig-Maximilians-Universität Munich, Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Lindwurmstr, 4, D-80337, Munich, Germany;

关键词: Sarcopenia;    Metabolomics;    Energy metabolism;    Mitochondrial metabolism;    Fatty acid metabolism;    Lipid metabolism;    Fatty acid oxidation;   

DOI  :  10.1186/s13395-022-00312-w

 received in 2022-08-10, accepted in 2022-12-13,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundSarcopenia 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.MethodsPlasma 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.ResultsUsing 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.ConclusionsWe 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.

【 授权许可】

CC BY   
© The Author(s) 2023

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