Specific lysophosphatidylcholine and acylcarnitine related to sarcopenia and its components in older men

Abstract

Background Metabolic profiling may provide insights into the pathogenesis and identification of sarcopenia; however, data on the metabolic basis of sarcopenia and muscle-related parameters among older adults remain incompletely understood. This study aimed to identify the associations of metabolites with sarcopenia and its components, and to explore metabolic perturbations in older men, who have a higher prevalence of sarcopenia than women. Methods We simultaneously measured the concentrations of amino acids, carnitine, acylcarnitines, and lysophosphatidylcholines (LPCs) in serum samples from a cross-sectional study of 246 Chinese older men, using targeted metabolomics. Sarcopenia and its components, including skeletal muscle index (SMI), 6-m gait speed, and handgrip strength were assessed according to the algorithm of the Asian Working Group for Sarcopenia criteria. Associations were determined by univariate and multivariate analyses. Results Sixty-five (26.4%) older men with sarcopenia and 181 (73.6%) without sarcopenia were included in the study. The level of isovalerylcarnitine (C5) was associated with the presence of sarcopenia and SMI. Regarding the overlapped metabolites for muscle parameters, among ten metabolites associated with muscle mass, six metabolites including leucine, octanoyl-L-carnitine (C8), decanoyl-L-carnitine (C10), dodecanoyl-L-carnitine (C12) and tetradecanoyl-L-carnitine (C14), and LPC18:2 were associated with handgrip strength, and three of which (C12, C14, and LPC18:2) were also associated with gait speed. Specifically, tryptophan was positively associated and glycine was negatively associated with handgrip strength, while glutamate was positively correlated with gait speed. Isoleucine, branched chain amino acids, and LPC16:0 were positively associated with SMI. Moreover, the levels of LPC 16:0,18:2 and 18:0 contributed significantly to the model discriminating between older men with and without sarcopenia, whereas there were no significant associations for other amino acids, acylcarnitines, and LPC lipids. Conclusions These results showed that specific and overlapped metabolites are associated with sarcopenic parameters in older men. This study highlights the potential roles of acylcarnitines and LPCs in sarcopenia and its components, which may provide valuable information regarding the pathogenesis and management of sarcopenia.

The Effect of Metabolites on Mitochondrial Functions in the Pathogenesis of Skeletal Muscle Aging

“…Multiple studies have demonstrated that the serum concentration of BCAAs decreases in patients with sarcopenia in comparison to elderly people without sarcopenia. [14][15][16][17] BCAAs refer to leucine, valine, and isoleucine, which are essential amino acids that can only be obtained from dietary sources and cannot be synthesized indigenously. They are involved in muscle protein synthesis, satellite cell activation, and proteolysis inhibition.…”

“…Serum levels of glutamate were found to differ between elderly patients with sarcopenia and those without sarcopenia. 17,41,64 Li et al observed that the serum level of glutamate was positively correlated with gait speed in elderly male patients with sarcopenia living in Beijing communities. 17 Gait speed is an important index to measure the life span and physical function of the elderly.…”

“…17,41,64 Li et al observed that the serum level of glutamate was positively correlated with gait speed in elderly male patients with sarcopenia living in Beijing communities. 17 Gait speed is an important index to measure the life span and physical function of the elderly. 64 Stefano et al reported that serum glutamate level was significantly associated with muscle mass and strength in Caucasian women.…”

“…The higher the serum concentration of these metabolites, the worse the physical function of patients with sarcopenia. 17,97 The toxic effects of fatty acids and their acylcarnitine derivatives mainly depend on the saturation and chain length of fatty acids, and thus, saturated long-chain fatty acids are the most lipotoxic. LCFA comprise all fatty acids with more than 12 carbon atoms in the chain, of which palmitic acid and stearic acid and their acylcarnitine derivatives are the most harmful to muscle function.…”

“…Observational studies have shown a significant downward trend in the serum levels of lysophosphatidylcholine (LPC) in patients with sarcopenia, indicating that LPC is one of the characteristic metabolites distinguishing elderly people with and without sarcopenia. 17,97,103 The serum levels of LPCs contributing significantly to this discrimination between elderly people with and without sarcopenia are LPC 16:0, LPC 18:0, and LPC 18:2, which are also the most abundant LPC present in human plasma.…”