Combined Plasma DHA-Containing Phosphatidylcholine PCaa C38:6 and Tetradecanoyl-Carnitine as an Early Biomarker for Assessing the Mortality Risk among Sarcopenic Patients.

The coming of the hyper-aged society in Taiwan prompts us to investigate the relationship between the metabolic status of sarcopenic patients and their most adverse outcome-death. We studied the association between any plasma metabolites and the risk for mortality among older Taiwanese sarcopenic patients. We applied a targeted metabolomic approach to study the plasma metabolites of adults aged ≥65 years, and identified the metabolic signature predictive of the mortality of sarcopenic patients who died within a 5.5-year follow-up period. Thirty-five sarcopenic patients who died within the follow-up period (Dead cohort) had shown a specific plasma metabolic signature, as compared with 54 patients who were alive (Alive cohort). Only 10 of 116 non-sarcopenic individuals died during the same period. After multivariable adjustment, we found that sex, hypertension, tetradecanoyl-carnitine (C14-carnitine), and docosahexaenoic acid (DHA)-containing phosphatidylcholine diacyl (PCaa) C38:6 and C40:6 were important risk factors for the mortality of sarcopenic patients. Low PCaa C38:6 levels and high C14-carnitine levels correlated with an increased mortality risk; this was even the same for those patients with hypertension (HTN). Our findings suggest that plasma PCaa C38:6 and acylcarnitine C14-carnitine, when combined, can be a better early biomarker for evaluating the mortality risk of sarcopenia patients.

Plasma acylcarnitine in elderly Taiwanese: as biomarkers of possible sarcopenia and sarcopenia.

BACKGROUND: Sarcopenia is defined as the disease of muscle loss and dysfunction. The prevalence of sarcopenia is strongly age-dependent. It could bring about disability, hospitalization, and mortality. The purpose of this study was to identify plasma metabolites associated with possible sarcopenia and muscle function to improve disease monitoring and understand the mechanism of muscle strength and function decline. METHODS: The participants were a group of healthy older adult who live in retirement homes in Asia (Taiwan) and can manage their daily lives without assistance. The participants were enrolled and divided into four groups: control (Con, n = 57); low physical function (LPF, n = 104); sarcopenia (S, n = 63); and severe sarcopenia (SS, n = 65) according to Asian countries that used Asian Working Group for Sarcopenia (AWGS) criteria. The plasma metabolites were used and the results were calculated as the difference between the control and other groups. RESULTS: Clinical parameters, age, gender, body mass index (BMI), hand grip strength (HGS), gait speed (GS), blood urea nitrogen (BUN), hemoglobin, and hematocrit were significantly different between the control and LPF groups. Metabolite patterns of LPF, S, and SS were explored in our study. Plasma kynurenine (KYN) and acylcarnitines (C0, C4, C6, and C18:1-OH) were identified with higher concentrations in older Taiwanese adults with possible sarcopenia and S compared to the Con group. After multivariable adjustment, the data indicate that age, BMI, and butyrylcarnitine (C4) are more important factors to identify individuals with low physical function and sarcopenia. CONCLUSION: This metabolomic study raises the importance of acylcarnitines on muscle mass and function. It suggests that age, BMI, BUN, KYN, and C4/Cr can be important evaluation markers for LPF (AUC: 0.766), S (AUC: 0.787), and SS (AUC: 0.919).

Alternations of Lipoprotein Profiles in the Plasma as Biomarkers of Huntington's Disease.

Alterations in lipid composition and disturbed lipoprotein metabolism are involved in the pathomechanism of Huntington's disease (HD). Here, we measured 112 lipoprotein subfractions and components in the plasma of 20 normal controls, 24 symptomatic (sympHD) and 9 presymptomatic (preHD) HD patients. Significant changes were found in 30 lipoprotein subfractions and components in all HD patients. Plasma levels of total cholesterol (CH), apolipoprotein (Apo)B, ApoB-particle number (PN), and components of low-density lipoprotein (LDL) were lower in preHD and sympHD patients. Components of LDL4, LDL5, LDL6 and high-density lipoprotein (HDL)4 demonstrated lower levels in preHD and sympHD patients compared with controls. Components in LDL3 displayed lower levels in sympHD compared with the controls, whereas components in very low-density lipoprotein (VLDL)5 were higher in sympHD patients compared to the controls. The levels of components in HDL4 and VLDL5 demonstrated correlation with the scores of motor assessment, independence scale or functional capacity of Unified Huntington's Disease Rating Scale. These findings indicate the potential of components of VLDL5, LDL3, LDL4, LDL5 and HDL4 to serve as the biomarkers for HD diagnosis and disease progression, and demonstrate substantial evidence of the involvement of lipids and apolipoproteins in HD pathogenesis.

Kynurenine Pathway of Tryptophan Metabolism Is Associated with Hospital Mortality in Patients with Acute Respiratory Distress Syndrome: A Prospective Cohort Study.

Acute respiratory distress syndrome (ARDS) involves dysregulated immune-inflammatory responses, characterized by severe oxidative stress and high mortality. Metabolites modulating the inflammatory and immune responses may play a central role in the pathogenesis of ARDS. Most biogenic amines may induce the production of reactive oxygen species, oxidative stress, mitochondrial dysfunction, and programmed cell death. We conducted a prospective study on metabolic profiling specific to the amino acids and biogenic amines of 69 patients with ARDS. Overall, hospital mortality was 52.2%. Between day 1 and day 7 after ARDS onset, plasma kynurenine levels and the kynurenine/tryptophan ratio were significantly higher among non-survivors than in survivors (all p < 0.05). Urine metabolic profiling revealed a significantly higher prevalence of tryptophan degradation and higher concentrations of metabolites downstream of the kynurenine pathway among non-survivors than among survivors upon ARDS onset. Cox regression models revealed that plasma kynurenine levels and the plasma kynurenine/tryptophan ratio on day 1 were independently associated with hospital mortality. The activation of the kynurenine pathway was associated with mortality in patients with ARDS. Metabolic phenotypes and modulating metabolic perturbations of the kynurenine pathway could perhaps serve as prognostic markers or as a target for therapeutic interventions aimed at reducing oxidative stress and mortality in ARDS.

Critical role of triglycerides for adiponectin levels in hepatitis C: a joint study of human and HCV core transgenic mice.

BACKGROUND: Both hepatitis C virus (HCV) infection and adiponectin are critically involved in metabolism. The reversal and associations of altering adiponectin levels after sustained virological responses (SVRs) following direct-acting antivirals (DAA) in HCV-infected patients remained elusive. METHODS: A joint study was conducted in a prospective cohort of 427 HCV-infected patients and a line of HCV core transgenic mice. RESULTS: Of 427, 358 had completed a course of DAA therapy and 353 had SVRs. At baseline, male sex (95% CI ß: - 1.44 to - 0.417), estimated glomerular filtration rate (eGFR) (- 0.025 to - 0.008), triglycerides (- 0.015 to - 0.005), and fibrosis-4 levels (0.08-0.297) were associated with adiponectin levels; BMI (0.029-0.327) and triglycerides levels (0.01-0.03) were associated with homeostatic model assessment for insulin resistance (HOMA-IR) in HCV-infected patients. At 24-week post-therapy, in SVR patients, male sex (- 1.89 to - 0.5) and eGFR (- 0.02 to - 0.001) levels were associated with adiponectin levels, levels of BMI (0.094-0.335) and alanine transaminase (0.018-0.078) were associated with HOMA-IR; compared with baseline levels, adiponectin levels decreased (6.53 ± 2.77 vs. 5.45 ± 2.56 µg/mL, p < 0.001). In 12-month-old HCV core transgenic mice with hepatic steatosis, triglyceride levels (0.021-0.111) were associated with adiponectin levels, and hepatic adipopnectin expression was comparable with that of control mice. CONCLUSIONS: Triglycerides and hepatic fibrosis are associated with HCV-specific alteration of adiponectin levels, and adiponectin may affect insulin sensitivity through triglycerides during HCV infection. In DAA-treated patients, after SVR, adiponectin levels decreased and the linking function of triglycerides between adiponectin and insulin sensitivity vanished. Moreover, HCV core with hepatic steatosis might affect extrahepatic adiponectin expression through triglycerides.

Recovery of lipid metabolic alterations in hepatitis C patients after viral clearance: Incomplete restoration with accelerated ω-oxidation.

BACKGROUND: How hepatitis C virus (HCV)-associated lipid metabolic alterations recover after sustained virological response (SVR) remains elusive. OBJECTIVE: The aforementioned recovery pattern was investigated. METHODS: In a prospective cohort study of 438 chronic hepatitis C (CHC) patients with SVR after anti-HCV therapy, 164 sex- and age-matched genotype I (G1) and G2 patients underwent paired-serum liquid chromatography-tandem mass spectrometry analyses before and 24 weeks after therapy. Subjects without CHC served as controls (n = 100). RESULTS: CHC patients had lower baseline lipid levels than controls. Among CHC patients, pre-therapy total cholesterol levels were positively associated with HCV RNA levels; G1 patients had higher pre-therapy HCV RNA levels than G2 patients. Repeated measures analysis of variance of CHC patients showed that lathosterol, lanosterol, total hydroxysphingomyelin, and total phosphatidylcholines levels, and total dicarboxyacylcarnitine/total acylcarnitine (indicators of ω-oxidation) and pre-ß-lipoprotein ratios elevated 24 weeks after therapy compared with the levels before therapy. Levels of total lysophosphatidylcholines and α- and ß-lipoprotein ratios decreased. Subgroup analyses showed elevated 7-dehydrocholesterol and lanosterol levels, particularly in G2 and male patients, who had broader spectra of altered phosphatidylcholines and acylcarnitines than G1 and female patients, respectively. Compared with controls, CHC patients had higher post-therapy levels of total lysophosphatidylcholines and hydroxysphingomyelins and ratios of total dicarboxyacylcarnitines/total acylcarnitines but lower cholesterol levels. CONCLUSIONS: At 24 weeks after therapy, accelerated cholesterol biosynthesis, hepatic lipid export, ω-oxidation, and decreased systemic inflammation were noted in CHC patients with SVR, with greater efficiency in G2 and male patients. Regardless, HCV-associated lipid metabolic alterations required >24 weeks for restoration or were incompletely reversible after SVR.

Nicotinuric acid: a potential marker of metabolic syndrome through a metabolomics-based approach.

OBJECTIVE: Metabolic syndrome is a multiplex disorder and puts patients on the road to type 2 diabetes and atherosclerotic cardiovascular diseases. However, a surrogate biomarker in plasma or urine in fully reflecting features of metabolic syndrome has not been explored. RESEARCH DESIGN AND METHODS: Urine metabolomics has potential utility in metabolic profiling because urine metabolites analysis reflects global outflux of metabolic change. Accordingly, we collected data on subjects (n = 99) with overweight, dyslipidemia, hypertension or impaired glucose tolerance and took a metabolomics approach to analyze the metabolites of urine revealed in metabolic syndrome by high-performance liquid chromatography-time-of-flight mass spectrometry and elicit potential biomarkers to picture metabolic syndrome. RESULTS: Our results revealed that the urine nicotinuric acid value of subjects with diabetes (HbA1c ≥ 6.5% or those receiving diabetes medications) (n = 25) was higher than subjects without diabetes (n = 37) (221 ± 31 vs. 152 ± 13 × 10(3) mAU, P = 0.0268). Moreover, urinary nicotinuric acid level was positively correlated with body mass index, blood pressure, total cholesterol, low-density lipoprotein cholesterol, triacylglycerol and high sensitivity C-reactive protein, but negatively correlated with high-density lipoprotein cholesterol. CONCLUSIONS: This is the first study, to our knowledge, to propose that nicotinuric acid represents an important pathogenic mechanism in process from metabolic syndrome to diabetes and atherosclerotic cardiovascular disease.