A study by Wu LC et al. found that BMI was significantly higher in non-myasthenic patients compared to myasthenic patients, with a 0.45-fold reduction in the odds of myasthenia gravis for every 1 kg /㎡ increase in BMI, and that higher BMI resulted in a lower risk of developing myasthenia gravis[15]. However, BMI remains controversial in the assessment of sarcopenia in older adults because BMI and does not distinguish between adiposity and lean body mass, and increased lean body mass results in decreased mortality[16]. Aging is associated with an increase in visceral adiposity and progressive loss of muscle mass, which has an opposite effect on mortality[17].Santos et al. evidence suggests that sarcopenia with obesity may be associated with higher levels of metabolic disorders and an increased risk of death compared with obesity or sarcopenia alone[18].
In line with previous findings, higher levels of Alb were significantly associated with non-muscular hypomuscular disorders in the elderly[19]. Albumin, the most abundant plasma protein in the body, is recognized as a very important plasma protein in the assessment of the body's nutritional status, and its reduction affects wound healing, lowers immunity and reduces lean body mass[20]. In the Smith S. et al. study, albumin levels were associated with poorer physical function and lower muscle strength or muscle mass in older adults; however, this association has not been confirmed in other populations[21].
This contradicts previous findings that serum TC, TG, and LDL levels were significantly lower in the sarcopenia group versus the non-sarcopenia group, whereas HDL was not significantly different between groups. The reason for the difference is not clear, but may lie in environmental or age range differences between the included and our study populations.
The decline in muscle mass, strength, and function associated with sarcopenia can lead to poor clinical outcomes and a loss of independence in older adults. A study by Francesco Landi et al. showed that by comparing patients with sarcopenia to non-sarcopenic patients during a 2-year follow-up period, it was found that sarcopenic patients were more than three times more likely to fall than their counterparts[23]. Therefore, the analysis of metabolites associated with reduced muscle mass and strength in the elderly is important for the identification of sarcopenia as well as for early prevention and treatment.
The results of this paper show that differences in amino acid and fatty acid metabolic profiles do exist in the plasma of patients with sarcopenia, and by analyzing the conditions associated with possible abnormalities in amino acid and fatty acid metabolic pathways, the results suggest that arginine, leucine, histidine, palmitic acid, and carnitine play important roles in the development of sarcopenia, and can be used as potential biomarkers for muscle mass and sarcopenia prediction.
Proteins consumed through the diet can be degraded in the body by lysosomes and proteasomes to amino acids, whose main function in the body is to synthesize peptides and proteins, but can also be converted to other compounds. Amino acid availability is a major regulator of mTOR signaling and muscle protein synthesis in human skeletal muscle, and leucine, in particular, is responsible for the anabolic effects of amino acids in skeletal muscle. Leucine is both an insulinotropic secretagogue and a trophic activator of rapamycin (mTOR) in skeletal muscle. Increased leucine promotes the phosphorylation and activation of downstream effectors of mTOR and may enhance the phosphorylation of Akt/ PKB (an upstream regulator of mTOR) by increasing the action of insulin, affecting translation initiation and muscle protein synthesis[24]. The primary cellular energy sensor in human muscle cells is AMPK[25], which catalyzes a modest decrease in the phosphorylation of the α-subunit following the ingestion of essential amino acids to abrogate the inhibition of mTOR by TSC 2 and/or to help augment protein synthesis by eliminating the negative regulation of eEF 2[24]. Multiple branched-chain amino acid (BCAA) levels have been found to correlate with thigh muscle cross-sectional area (CSA) in older adults[26], and increasing the amount of leucine in a given diet may be able to promote muscle protein synthesis in older adults[27].Consistent with previous studies, sarcopenia is associated with reduced non-fasting plasma concentrations of the BCAAs leucine and isoleucine, as well as with reduced absolute protein intake[28]. Malnutrition is considered to be a strong predictor of sarcopenia[29], and increasing levels of amino acids in the body can help stimulate muscle protein synthesis[30].Smith.L.W. found that arginine-mediated NO release can improve tissue perfusion through mechanisms such as vasodilation and angiogenesis, and that endogenous NO is associated with the induction of skeletal muscle fiber hypertrophy by reducing protein degradation and increasing protein synthesis closely associated with the induction of skeletal muscle fiber hypertrophy by decreasing protein degradation and increasing protein synthesis, and through these actions can lead to better muscle tissue utilization of nutrients (glucose, fatty acids, and amino acids). In this case, the cells can produce more ATP[31], and it has been shown that arginine protects myocytes from depletion by stimulating protein synthesis during catabolic conditions in C2 C12 cells[32], possibly related to the stimulation of protein synthesis by L-Arg in a NO-dependent manner through activation of the mTOR pathway[32][33].It has been demonstrated in animal experiments by K. Yao that L-Arg enhances protein synthesis and metabolism in skeletal muscle cells and L-Arg supplementation is beneficial in helping burn patients maintain muscle mass[34], and that increased nutritional support for skeletal muscle cells also contributes to glycolipid metabolism, thereby preventing muscle fat infiltration. Another animal experiment suggests that the concentration of the histidine metabolite N-methylhistidine is a sensitive indicator of myofibrillar protein degradation in starved rats. During proteolysis, 3-MH (3-Methylhistidine is released into the blood but cannot be reused. Therefore, plasma concentration and urinary excretion of 3-MH are sensitive markers of myofibrillar protein degradation and may be used as biomarkers for the diagnosis of sarcopenia[35]. β-Alanyl-histidine is the only myopeptide present in human muscle and most of it is found in skeletal muscle[36], and it has been shown that histidyl-containing dipeptides act as intracellular buffers, metal ion chelators, antioxidants, and/or free radical scavengers, and have some significance for the protection of myocytes[37]. Creatine phosphate is more abundant in skeletal muscle as a form of energy storage. Creatine is synthesized using glycine as the backbone, arginine to provide the amidine group, and S-adenosylmethionine to provide the methyl group, and catalyzed by creatine kinase, creatine receives the high-energy phosphoryl bonding group of ATP to form phosphocreatine, which is particularly important for exercise-type skeletal muscle function. Decreased skeletal muscle mass has also been found to correlate with reduced serum levels of phosphocreatine in the elderly[38]. Most of the amino acids in the body can undergo transamination under the action of aminotransferase, reversibly transferring the amino group of a-amino acid to a-keto acid, as a result of which the amino acid is deaminated to generate the corresponding a-keto acid, and the original a-keto acid is transformed into another amino acid, such as leucine and isoleucine in the body can be transformed into ketone bodies and enter into lipid metabolism pathway, which can suggest that the amino acid metabolism is closely related to the lipid metabolism. It can be suggested that amino acid metabolism is closely related to lipid metabolism.
Fat in white adipocytes, under the action of hormone-sensitive triglyceride lipase (HSL) and adipose tissue triglyceride lipase (ATGL), is broken down to produce fatty acids and glycerol, and subsequently, fatty acids pass through the B oxidation pathway to produce lipoyl CoA catalyzed by lipoyl CoA synthetase, and lipoyl CoA crosses through the inner mitochondrial membrane under the action of carnitine and then is catalyzed by carnitine-lipoyltransferase I After crossing the inner mitochondrial membrane in the presence of carnitine and catalyzed by carnitine-lipoyltransferase I, lipoyl CoA combines with carnitine to form lipoyl carnitine, which is then converted to lipoyl CoA and released from carnitine by carnitine-lipoyltransferase II after crossing the inner mitochondrial membrane in the presence of carnitine. Previous studies have explored the role of fatty acids in sarcopenia. Palmitic acid, the most abundant circulating saturated fatty acid, may have an effect on muscle tissue, and it has been suggested that palmitic acid induces lipid droplet accumulation and insulin resistance in skeletal muscle by inhibiting the expression of IRS-α 1 (a key molecule in the insulin signaling pathway) and GLUT-α 4 (an important glucose transporter protein), which play an important role in the maintenance of glucose homeostasis and insulin sensitivity play an important role in the maintenance of glucose homeostasis and insulin sensitivity[39]. In addition, it has been shown that MOTS-c is associated with palmitic acid-induced sarcopenia[40], and that the fibroblast factor FGF19 can ameliorate palmitic acid-induced muscle atrophy, glucose and lipid metabolism disorders[39]. palmitic acid, as a type of fatty acid, interacts with carnitine in metabolism, and carnitine levels correlate with insulin resistance. It has also been shown that carnitine levels correlate with grip strength and gait speed in older men with sarcopenia [41], and these results could aid in the prevention and treatment of sarcopenia, which brings important implications for patients and the healthcare system. Palmitate was found to cause lipotoxicity-mediated loss of myofibers, and treatment with palmitate resulted in a reduction in the number, width, and length of myotubes in a dose-dependent manner [42]. Oleate protects skeletal myotube atrophy from the negative effects of palmitate, and one of the important factors in the regulation of myotube atrophy is the fatty acid-mediated mitochondrial redox state. One of the important factors in the regulation of myotube atrophy is the mitochondrial redox state mediated by fatty acids, and the key to mitochondrial fragmentation in skeletal muscle is the increase in mitochondrial ROS, which cause cellular damage through nonspecific modification and destruction of proteins, phospholipids, and DNA [43]. Park JM et al. demonstrated that hispidin protects the C2 C12 myotubes from oxidative stress induced by palmitate [44]. Myotubes were significantly atrophied, MuRf1 expression was increased, myosin heavy chain protein content was decreased, and SGLT 2 i resulted in a reduction in visceral fat accumulation and also led to an increase in muscle mass and grip strength, as well as a decrease in muscle and serum saturated fatty acid levels, especially palmitic acid, after SGLT 2 i administration [45]. Kenneth D' Souza et al. demonstrated that whey peptides promote adipocyte differentiation and lipid accumulation, promote mitochondrial fatty acid oxidation in 3 T3-L1 adipocytes, as well as ameliorate palmitic acid-induced insulin resistance, which was associated with a reduction in endoplasmic reticulum stress, inflammation, and accumulation of diglycerides by whey peptides [46].Consistent with previous studies, high and low levels of carnitine are associated with lower limb dysfunction in the elderly, and the correlation is especially pronounced with levels of medium- and long-chain acylcarnitines[41].A clinical trial by Malaguarnera, M., et al. found improved physical and cognitive function in 70 centenarians treated with L-carnitine for a period of 6 months[47]. On the other hand, several studies have found that elevated levels of carnitine can predict the development of diabetes[48]. This may be due to the fact that medium- and long-chain acylcarnitines are elevated in the presence of vascular inflammation and insulin resistance[49]. Diabetes is associated with weakness and loss of mobility through low-grade inflammation, metabolic acidosis and insulin resistance, altering intracellular energy production and muscle contraction[50]. Thus, these mechanisms may help clarify the association between high levels of acylcarnitines and impaired physical function.
Consistent with previous findings, the results of the present study reveal significant differences in the metabolism of amino acids and fatty acids between sarcopenic and non-sarcopenic patients. This study has both limitations and unique strengths. First, the limitations are that our study population consisted mainly of outpatients in a general hospital, with a relatively small sample size, and that they were taking a wide range of medications, were generally older, and were often accompanied by the coexistence of multiple diseases. Such conditions may have an effect on serologic metabolites, but we cannot completely rule out the influence of other diseases or medications taken on metabolites. In addition, the large number of influencing factors may have biased the results somewhat, and future studies should control for these confounding factors as much as possible. In addition, due to the lack of long-term follow-up and follow-up, we were unable to obtain useful information about the long-term effects of these metabolites on patients with sarcopenia. However, the main strength of this study is that we can provide new perspectives for understanding the mechanisms and potential causes of myasthenia gravis by identifying pointers to markers and metabolic pathways.