Carnitine Levels Research Articles

Hypocarnitinemia and its effect on seizure control in adult patients with intractable epilepsy on the modified Atkins diet.

Previous studies have demonstrated the safety and efficacy of the modified Atkins diet (MAD) in attenuating seizures in patients with intractable epilepsy. MAD works by achieving ketosis, which is heavily dependent on the metabolic compound, carnitine, to facilitate the transport of long-chain fatty acids across the mitochondria for beta-oxidation. The effect of carnitine on ketogenic diet therapy is not well-defined in the current literature. Thus, the purpose of our study is to investigate the effects of hypocarnitinemia on the efficacy of MAD. A retrospective chart review was conducted, and 58 adults with epilepsy undergoing MAD were evaluated. Generalized linear mixed effects models were used to compare the low carnitine status with normal carnitine group in patient measures of body mass index, seizure frequency and severity, number of anti-seizure medications, beta-hydroxybutyrate, triglyceride, and carnitine levels across baseline, 3-9-month follow-up (timepoint 1), 1-2-year follow-up (timepoint 2), and 2+ year follow-up (timepoint 3). Our study revealed that 38.3% of adult patients with epilepsy following MAD experienced low free carnitine at some point through the course of diet therapy. Patients with hypocarnitinemia at timepoint 2 showed a significant percent seizure increase while seizures continued to decrease in the normal carnitine group. Fasting triglyceride levels at timepoint 1 were significantly increased in the low carnitine group compared to normal carnitine group. Change in BHB, BMI, seizure severity, and number of ASMs showcased no significant differences between the low and normal carnitine groups. It may be important for clinicians to monitor for hypocarnitinemia in adults on MAD and provide carnitine supplementation when low. Further investigations into carnitine and MAD may inform clinical decisions on carnitine supplementation to maximize the efficacy of MAD therapy.

Clinical phenotypic and genotypic analysis of 5 pediatric patients with β-ketothiolase deficiency

Objective: To summarize the clinical and genetic characteristics of children with β-ketothiolase deficiency (BKTD). Methods: The clinical characteristics, biochemical, markers detected by tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), as well as the variants in ACAT1 gene among 5 children with BKTD in Children's Hospital of Chongqing Medical University between October 2018 and December 2022 were retrospectively analyzed. Results: The onset age of the disease in 5 patients (4 males and 1 female) ranged from 9.7 to 28.0 months. During the acute phase, severe metabolic acidosis was observed with a pH of 6.9-7.1, as well as hypoglycaemia (2.3-3.4 mmol/L) and positive urinary ketone bodies (+-++++). Blood levels of methylcrotonyl carnitine, methylmalonyl carnitine and malonyl carnitine were 0.03-0.42, 0.34-1.43 and 0.83-3.53 μmol/L respectively and were significantly elevated. Urinary 2-methyl-3-hydroxybutyric acid was 22-202 and 3-hydroxybutyric acid was 4-6 066, both were higher than the normal levels. Methylcrotonylglycine was mild elevated (0-29). The metabolites detected by MS/MS and GC/MS were significantly reduced after treatment. Analysis of ACAT1 gene mutation was performed in 5 children. Most variants were missense (8/9). Four previously unreported variants were identified: c.678G>T (p.Trp226Cys), c.302A>G (p.Gln101Arg), c.627_629dupTGA (p.Asn209_Glu210insAsp) and c.316C>T (p.Gln106Ter), the first 2 variants were predicted to be damaging by SIFT, PolyPhen-2 and Mutation Taster software. c.316C>T (p.Gln106Ter) is a nonsense variant. Conclusions: β-ketothiolase deficiency is relatively rare, lacks specific clinical manifestations, however severe metabolic acidosis, hypoglycemia, and ketosis during the acute onset were consistent findings. Missense mutations in the ACAT1 gene are common genetic causes of β-ketothiolase deficiency.

A novel pathogenic variant in the carnitine transporter gene, SLC22A5, in association with metabolic carnitine deficiency and cardiomyopathy features

BackgroundPrimary carnitine deficiency (PCD) denotes low carnitine levels with an autosomal recessive pattern of inheritance. Cardiomyopathy is the most common cardiac symptom in patients with PCD, and early diagnosis can prevent complications. Next-generation sequencing can identify genetic variants attributable to PCD efficiently.ObjectiveWe aimed to detect the genetic cause of the early manifestations of hypertrophic cardiomyopathy and metabolic abnormalities in an Iranian family.MethodsWe herein describe an 8-year-old boy with symptoms of weakness and lethargy diagnosed with PCD through clinical evaluations, lab tests, echocardiography, and cardiac magnetic resonance imaging. The candidate variant was confirmed through whole-exome sequencing, polymerase chain reaction, and direct Sanger sequencing. The binding efficacy of normal and mutant protein-ligand complexes were evaluated via structural modeling and docking studies.ResultsClinical evaluations, echocardiography, and cardiac magnetic resonance imaging findings revealed hypertrophic cardiomyopathy as a clinical presentation of PCD. Whole-exome sequencing identified a new homozygous variant, SLC22A5 (NM_003060.4), c.821G > A: p.Trp274Ter, associated with carnitine transport. Docking analysis highlighted the impact of the variant on carnitine transport, further indicating its potential role in PCD development.ConclusionsThe c.821G > A: p.Trp274Ter variant in SLC22A5 potentially acted as a pathogenic factor by reducing the binding affinity of organic carnitine transporter type 2 proteins for carnitine. So, the c.821G > A variant may be associated with carnitine deficiency, metabolic abnormalities, and cardiomyopathic characteristics.

Comparison of metabolic parameters between oral and total parenteral nutrition in children with severe eating disorders.

This study investigated changes of lipid parameters in children with severe eating disorders during refeeding in order to explore the optimal timing for lipid preparation administration. We prospectively assessed the physical conditions of patients with eating disorders after the start of nutrition therapy. The assessments were performed at admission and at 2 and 4 weeks. Lipid metabolism was assessed based on triglyceride (TG), total cholesterol (TC), and free carnitine (FC) levels, as well as acylcarnitine/free carnitine (AC/FC) ratio. A total of 18 patients were included. Of these, 12 and 6 received an oral diet (OD group) and total parenteral nutrition (TPN group), respectively. The mean body mass indexes at hospital admission were 12.8 kg/m2 in the OD group and 12.7 kg/m2 in the TPN group. At 2 weeks after the start of refeeding, TC, TG, and AC/FC levels were significantly lower in the TPN group than in the OD group. Other blood test results did not show any significant differences between the two groups. Fat-free glucose-based nutrition promoted lipid metabolism over a 2-week period after the start of refeeding, suggesting that balanced energy and lipid intake are essential, even in TPN.

Comparison of metabolic parameters between oral and total parenteral nutrition in children with severe eating disorders.

This study investigated changes of lipid parameters in children with severe eating disorders during refeeding in order to explore the optimal timing for lipid preparation administration. We prospectively assessed the physical conditions of patients with eating disorders after the start of nutrition therapy. The assessments were performed at admission and at 2 and 4 weeks. Lipid metabolism was assessed based on triglyceride (TG), total cholesterol (TC), and free carnitine (FC) levels, as well as acylcarnitine/free carnitine (AC/FC) ratio. A total of 18 patients were included. Of these, 12 and 6 received an oral diet (OD group) and total parenteral nutrition (TPN group), respectively. The mean body mass indexes at hospital admission were 12.8 kg/m2 in the OD group and 12.7 kg/m2 in the TPN group. At 2 weeks after the start of refeeding, TC, TG, and AC/FC levels were significantly lower in the TPN group than in the OD group. Other blood test results did not show any significant differences between the two groups. Fat-free glucose-based nutrition promoted lipid metabolism over a 2-week period after the start of refeeding, suggesting that balanced energy and lipid intake are essential, even in TPN.

Downregulation of PDZK1 by TGF-β1 promotes renal fibrosis via inducing epithelial-mesenchymal transition of renal tubular cells

Transforming growth factor-beta 1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) of renal tubular cells promotes renal fibrosis and the progression of chronic kidney disease (CKD). PDZ domain-containing 1 (PDZK1) is highly expressed in renal tubular epithelial cells; however, its role in TGF-β1-induced EMT remains poorly understood. The present study showed that PDZK1 expression was extremely downregulated in fibrotic mouse kidneys and its negative correlation with TGF-β1 expression and the degree of renal fibrosis. In addition, TGF-β1 downregulated the mRNA expression of PDZK1 in a time- and concentration-dependent manner in vitro. The downregulation of PDZK1 exacerbated TGF-β1-induced EMT upon oxidative stress, while the overexpression of PDZK1 had the converse effect. Subsequent investigations demonstrated that TGF-β1 downregulated PDZK1 expression via p38 MAPK or PI3K/AKT signaling in vitro, but independently of ERK/JNK MAPK signaling. Meanwhile, inhibition of the p38/JNK MAPK or PI3K/AKT signaling using chemical inhibitors restored the PDZK1 expression, mitigated renal fibrosis, and elevated renal levels of endogenous antioxidants carnitine and ergothioneine in adenine-induced CKD mice. These findings provide the first evidence suggesting a negative correlation between PDZK1 and renal fibrosis, and identifying PDZK1 as a novel suppressor of renal fibrosis in CKD through ameliorating oxidant stress.

The influence of increased protein intake and L-carnitine supply on the outcomes of term newborns in intensive therapy

We studied the possibilities of increased protein and L-carnitine supplementation in full-term newborns with perinatal diseases to improve the results of intensive care. Aim: to assess the impact of short-term increased protein consumption and L-carnitine supplementation by full-term newborns on the main indicators of treatment effectiveness in the intensive care unit. Materials and methods. To check the impact of the proposed method of feeding newborns, the life indicators of 59 full-term children, who were randomly divided into two groups, were studied. The first group (n = 30) received standard nutrition with mother’s milk or formula, the second group (n = 29) received a food product fortified with a protein supplement and a subsidy of L-carnitine during hospital stay. Results. Infants of both groups had statistically equivalent anthropometric characteristics at the beginning of the study. The proportions of infants of both sexes were within the 50 % percentile. Starting from the third week, caloric intake for the standard diet group (SG) and the enrichment group (FG), respectively, was 111.83 ± 7.19 kcal/kg/day, against 113.44 ± 5.61 kcal/kg/day, p = 0.0667. Per 1 g of protein, children in the FG group had amount of non-protein calories as 28.68 (27.50; 29.80) kcal/kg/day, compared to the indicator in the SG group of 42.37 (41.60; 38.00) kcal/kg/day, with U = 28.0000; p = 0.0001. Carnitine supplementation in the FG group led to an increase in the level of free carnitine in the last blood plasma samples, before the children were discharged home. In general, the proposed nutrition strategy was accompanied by better indicators of the physical development of children, and a statistically probable faster recovery of body weight in the fortification group. Thus, the generalized indicator of body weight of children of the SG group was 3966.90 ± 439.08 g, compared to the FG group of 3554.62 ± 452.28 g, with p = 0.0033. In general, children who consumed more protein were transferred from the intensive care unit earlier – 12.00 (11.00; 16.00) days, against 10.00 (8.00; 12.00) days, with U = 235,00; p = 0.0024; previously discharged from the hospital – 26.50 (22.00; 31.00) days, against 21.00 (19.00; 27.00) days, with U = 267.00, p = 0.0109. This strategy proved to be safe, as confirmed by normal levels of phenylalanine and urea at all stages of the examination of children. Conclusions. Short-term increased protein consumption against the background of carnitine supplementation improves the results of physical development of newborns and indicators of hospitalization and intensive care unit stay. Larger studies and catamnestic observation of children are needed.

BIOCHEMICAL PROFILE OF FULL-TERM NEWBORNS WITH DIFFERENT PROTEIN SUPPLY ON THE BACKGROUND OF THE TREATMENT OF CRITICAL DISEASES OF THE PERINATAL PERIOD

Study of the effect of increased protein and L-carnitine supplementation in term neonates with critical illnesses on the biochemical profile and improvement of intensive care outcomes.
 Objective: assessment of the impact of increased L-carnitine and protein supplementation on the physical development and biochemical profile of newborns who were in a critical condition.
 Materials and methods. The life indicators of 59 full-term children, who were randomly divided into two groups, were studied. The first group (n = 30) received standard nutrition with mother's milk or formula, the second group (n = 29) received protein-fortified food and L-carnitine supplementation during the hospital stay.
 The results. Babies of both groups had statistically equivalent characteristics at the beginning of the study. Against the background of higher consumption of proteins, the number of non-protein calories per 1 g of protein in the study group was 28.68 kcal/kg/day (27.50; 29.80), against the indicator of the standard diet group of 42.37 kcal/kg/day (41 .60; 38.00), with U = 28.0000; p = 0.000001. Carnitine supplementation in the GZ group led to an increase in the level of free carnitine in the last blood plasma samples of newborns. In general, the proposed nutrition strategy was accompanied by better indicators of physical development of children. Children who consumed more protein were transferred from the intensive care unit earlier – 10.00 (8.00; 12.00) days, against 12.00 (11.00; 16.00) days, with U = 235.00; p = 0.0024; previously discharged from the hospital -21.00 (19.00; 27.00) days, against 26.50 (22.00; 31.00) days at U = 267.00, p = 0.0109. This strategy proved to be safe, as confirmed by normal levels of phenylalanine and blood biochemical indicators at all stages of the examination of children, including urea nitrogen and creatinine.
 Conclusions. Short-term increased consumption of protein against the background of carnitine supplementation improves the results of the physical development of newborns, does not lead to deviations in the biochemical profile, and is safe.

Formononetin promotes fatty acid β-oxidation to treat non-alcoholic steatohepatitis through SIRT1/PGC-1α/PPARα pathway

BackgroundNon-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease (NAFLD), carries a high risk of cirrhosis and hepatocellular carcinoma. With the increasing incidence of NASH, the accompanying medical burden is also increasing rapidly, so the development of safe and reliable drugs is urgent. Formononetin (FMNT) has a variety of pharmacological effects such as antioxidant and anti-inflammation, and plays a major role in regulating lipid metabolism, reducing hepatic steatosis and so on, but the mechanism for alleviating NASH is unclear. Materials and methodsWe firstly established a mouse model on NASH through methionine-choline deficient (MCD) diet to investigate the improvement of FMNT as well as the effects of fatty acid β oxidation and SIRT1/PGC-1α/PPARα pathway. Then, we explored the mechanisms of FMNT regulation in SIRT1/PGC-1α/PPARα pathway and fatty acid β oxidation based on genes silencing of SIRT1 and PGC1A. In addition, SIRT1 agonist (SRT1720) and inhibitor (EX527) were used to verify the mechanism of FMNT on improvement of NASH. ResultsOur study found that after FMNT intervention, activities of ALT and AST and TG level were improved, and liver function and hepatocellular steatosis on NASH mice were significantly improved. The detection of β oxidation related indicators showed that FMNT intervention up-regulated FAO capacity, level of carnitine, and the levels of ACADM and CPT1A. The detection of factors related to the SIRT1/PGC-1α/PPARα pathway showed that FMNT activated and promoted the expression of SIRT1/PGC-1α/PPARα pathway, including up-regulating the expression level of SIRT1, improving the activity of SIRT1, promoting the deacetylation of PGC-1α, and promoting the transcriptional activity of PPARα. Furthermore, after genes silencing of SIRT1 and PGC1A, we found that FMNT intervention could not alleviate NASH, including improvement of hepatocellular steatosis, enhancement of β oxidation, and regulation of SIRT1/PGC-1α/PPARα pathway. Afterwards, we used SRT1720 as a positive control, and the results indicated that FMNT and SRT1720 intervention had no significant difference on improving hepatocellular steatosis and promoting fatty acid β oxidation. Besides, we found that when EX527 intervention inhibited expression of SIRT1, the improvement of FMNT on NASH was weakened or even disappeared. ConclusionIn summary, our results demonstrated that FMNT intervention activated SIRT1/PGC-1α/PPARα pathway to promote fatty acid β oxidation and regulate lipid metabolism in liver, ultimately improved hepatocellular steatosis on NASH mice.

Effect of statin treatment on metabolites, lipids and prostanoids in patients with Statin Associated Muscle Symptoms (SAMS).

Between 5-10% of patients discontinue statin therapy due to statin-associated adverse reactions, primarily statin associated muscle symptoms (SAMS). The absence of a clear clinical phenotype or of biomarkers poses a challenge for diagnosis and management of SAMS. Similarly, our incomplete understanding of the pathogenesis of SAMS hinders the identification of treatments for SAMS. Metabolomics, the profiling of metabolites in biofluids, cells and tissues is an important tool for biomarker discovery and provides important insight into the origins of symptomatology. In order to better understand the pathophysiology of this common disorder and to identify biomarkers, we undertook comprehensive metabolomic and lipidomic profiling of plasma samples from patients with SAMS who were undergoing statin rechallenge as part of their clinical care. We report our findings in 67 patients, 28 with SAMS (cases) and 39 statin-tolerant controls. SAMS patients were studied during statin rechallenge and statin tolerant controls were studied while on statin. Plasma samples were analyzed using untargeted LC-MS metabolomics and lipidomics to detect differences between cases and controls. Differences in lipid species in plasma were observed between cases and controls. These included higher levels of linoleic acid containing phospholipids and lower ether lipids and sphingolipids. Reduced levels of acylcarnitines and altered amino acid profile (tryptophan, tyrosine, proline, arginine, and taurine) were observed in cases relative to controls. Pathway analysis identified significant increase of urea cycle metabolites and arginine and proline metabolites among cases along with downregulation of pathways mediating oxidation of branched chain fatty acids, carnitine synthesis, and transfer of acetyl groups into mitochondria. The plasma metabolome of patients with SAMS exhibited reduced content of long chain fatty acids and increased levels of linoleic acid (18:2) in phospholipids, altered energy production pathways (β-oxidation, citric acid cycle and urea cycles) as well as reduced levels of carnitine, an essential mediator of mitochondrial energy production. Our findings support the hypothesis that alterations in pro-inflammatory lipids (arachidonic acid pathway) and impaired mitochondrial energy metabolism underlie the muscle symptoms of patients with statin associated muscle symptoms (SAMS).

Evaluation of fatty acids and carnitine as biomarkers of PFOS exposure in biota (fish and dolphin) from Galveston Bay and the northwestern Gulf of Mexico

Perfluorooctane sulfonate (PFOS) is a ubiquitous pollutant that elicits a wide range of toxic effects in exposed biota. Coastal zones in highly urbanized or industrial areas are particularly vulnerable to PFOS pollution. At present, information is lacking on biomarkers to assess PFOS effects on aquatic wildlife. This study investigated the efficacy of l-carnitine (or carnitine) and fatty acids as biomarkers of PFOS exposure in aquatic biota. The levels of PFOS, total and free carnitine, and 24 fatty acids (measured as fatty acid methyl esters or FAMEs) were measured in the liver, and muscle or blubber, of fish and dolphins sampled from Galveston Bay and the northern Gulf of Mexico (nGoM). Overall, bottlenose dolphins (Tursiops truncatus) had the highest hepatic PFOS levels. Galveston Bay fish, gafftopsail catfish (Bagre marinus), red drum (Sciaenops ocellatus), and spotted seatrout (Cynoscion nebulosus), had hepatic PFOS levels ∼8-13× higher than nGoM pelagic fish species, red snapper (Lutjanus campechanus) and yellowfin tuna (Thunnus albacares). The multivariate analysis of PFOS liver body-burdens and biomarkers found carnitine to be a more modal biomarker of PFOS exposure than FAMEs. Significant positive correlation of hepatic PFOS levels with total carnitine was evident for biota from Galveston Bay (fish only), and a significant correlation between PFOS and total and free carnitine was evident for biota from the nGoM (fish and dolphins). Given the essential role of carnitine in mediating fatty acid β-oxidation, our results suggest carnitine to be a likely candidate biomarker of environmental PFOS exposure and indicative of potential dyslipidemia effects.

L-Carnitine pretreatment ameliorates heat stress-induced acute kidney injury by restoring mitochondrial function of tubular cells.

A major complication of heat-related illness is the development of acute kidney injury (AKI) and damage to kidney tubular cells. Because kidney tubular cells use fatty acids as a major energy source, impaired fatty acid oxidation (FAO) may be associated with kidney injury due to heat stress. Carnitine is essential in the transportation of fatty acid into mitochondria for FAO. To date, there has been little attention given to the role of carnitine in heat-related illness and AKI. To evaluate the relationship between carnitine inadequacy and heat-related illness severity or AKI, we examined serum carnitine levels in patients with heat-related illness. We also used heat-stressed mice to investigate the effect of l-carnitine pretreatment on various kidney functions such as mitochondrial activity, proinflammatory changes in kidney macrophages, and histological damage. We observed an elevation in serum acylcarnitine levels, indicating carnitine insufficiency in patients with severe heat-related illness and/or AKI. l-Carnitine pretreatment ameliorated ATP production in murine tubular cell mitochondria and prevented a change in the kidney macrophage population dynamics observed in AKI: a decrease in tissue-resident macrophages, influx of bone marrow-derived macrophages, and change toward proinflammatory M1 polarization. In conclusion, carnitine insufficiency may be closely associated with severe heat-related illness and related AKI. Enhancement of the FAO pathway by l-carnitine pretreatment may prevent heat stress-induced AKI by restoring mitochondrial function.NEW & NOTEWORTHY Enhancing fatty acid oxidation (FAO) after acute kidney injury (AKI) improves renal outcomes. This report shows that carnitine insufficiency, which could inhibit FAO, correlates to severe heat-related illness and AKI in a clinical study. We also demonstrate that administering l-carnitine to mice improves mitochondrial respiratory function and prevents deleterious changes in renal macrophage, resulting in improved renal outcomes of heat-induced AKI. l-Carnitine may be an effective preventive treatment for severe heat-related illness and related AKI.

Myeloperoxidase, carnitine, and derivatives of reactive oxidative metabolites in heart failure with preserved versus reduced ejection fraction: A meta-analysis

BackgroundUnderstanding the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF) continues to be challenging. Several inflammatory and metabolic biomarkers have recently been suggested to be involved in HFpEF. ObjectivesThe purpose of this review was to synthesize the evidence on non-traditional biomarkers from metabolomic studies that may distinguish HFpEF from heart failure with reduced ejection fraction (HFrEF) and controls without HF. MethodsA systematic search was conducted using Medline and PubMed with search terms such as “HFpEF” and “metabolomics”, and a meta-analysis was conducted. ResultsMyeloperoxidase (MPO) levels were significantly (p < 0.001) higher in HFpEF than controls without HF, but comparable (p = 0.838) between HFpEF and HFrEF. Carnitine levels were significantly (p < 0.0001) higher in HFrEF than HFpEF, but comparable (p = 0.443) between HFpEF and controls without HF. Derivatives of reactive oxidative metabolites (DROMs) were not significantly (p = 0.575) higher in HFpEF than controls without HF. ConclusionThese data suggest that MPO is operative in HFpEF and HFrEF and may be a biomarker for HF. Furthermore, circulating carnitine levels may distinguish HFrEF from HFpEF.

Analysis of the difference in metabolites and gene expressions between pre-receptive and receptive endometria

To analyze the difference in the gene expression, amino acid and carnitine levels in the cervical secretions between the endometria of pre-receptive and receptive stages, with an aim to provide clues for identifying new molecular markers for endometrial receptivity. Fifty nine infertile women treated at the Department of Reproductive Medicine of Linyi People's Hospital from January 6, 2020 to January 31, 2022 were selected as as the study subjects, which were matched with 3 pairs (6 cases) of infertile women preparing for embryo transfer based on factors such as age, body mass index, and length of infertility. Endometrial tissue samples were collected for gene transcription and expression analysis. Twenty five women who had become pregnant through assisted reproductive technology were selected as the control group, and 28 non-pregnant women receiving ovulation monitoring at the Outpatient Department were enrolled as the case group. Status of endometrial receptivity was determined by ultrasonography. In the former group, endometrial tissues were sampled for sequencing, and GO and KEGG database enrichment analysis of differentially expressed genes was carried out. In the latter group, cervical secretions were collected, and amino acid and carnitine levels were measured by mass spectrometry. Statistical analysis was carried out using rank sum test, t test and chi-square test with SPSS v25.0 software. No difference was found in the clinical data of the patients with regard to age, body mass index, infertility years, AMH, FSH, LH, E2, and type of infertility. Compared with the receptive endometrial tissues, there were 100 significantly up-regulated genes and 191 significantly down-regulated genes in the pre-receptive endometrial tissue, with the most significantly altered ones being HLA-DRB5 and MMP10. The biological processes, molecular functions and pathways enriched by more differentially expressed genes in GO and KEGG were mainly immune regulation, cell adhesion and tryptophan metabolism. Analysis of secretion metabolism also revealed a significant difference in the levels of amino acids and carnitine metabolites between the two groups (P < 0.05), in particular those of Alanine, Valine, 3-hydroxybutyrylcarnitine (C4OH) + malonylcarnitine (C3DC)/captoylcarnitine (C10). A significant difference has been discovered in the levels of gene transcription and protein expression in the endometrial tissues from the pre-receptive and receptive stages. The levels of amino acids and carnitine, such as Alanine, Valine, 3-hydroxybutyryl carnitine (C4OH)+malonyl carnitine (C3DC)/caproyl carnitine (C10), may be associated with the receptive status of the endometrium, though this need to be verified with larger samples.

Serum Trimethylamine N-Oxide, Choline, Betaine, and Carnitine levels among Coronary Artery Disease patients

Background and aimRecent studies have linked Trimethylamine N-oxide (TMAO) to cardiovascular diseases; our study aimed to analyze the association between coronary artery disease (CAD) and TMAO. MethodsPubMed, Scopus, Embase, and Web of Science were searched using terms; such as “CAD” and “TMAO”. Only observational controlled studies were included. RevMan software version 5.4 was used for the analysis. ResultsA significant association was found between the CAD group and increased serum TMAO levels compared with the control group (MD = 1.16, 95% CI = 0.54 to 1.78, p-value =0.0003). This association remained significant among acute coronary syndrome (ACS) patients (MD=0.98, 95% CI =0.73 to 1.23, p-value <0.00001) and was also detected among young and old CAD patients (MD = 0.35, 95% CI = 0.06 to 0.64, p-value = 0.02 and MD = 1.36, 95% CI = 0.71 to 2.01, p-value <0.0001, respectively). On further analysis of intestinal metabolites, we detected an insignificant association between choline, betaine, carnitine, and CAD. According to our sensitivity analysis, TMAO is an acceptable discriminatory marker for CAD (0.721, SE was 0.0816, 95% CI 0.561 to 0.881). ConclusionTMAO is an acceptable discriminatory marker for CAD, with significantly higher levels among these patients regardless of their age. Other metabolites didn't show such an association. The role of serum level TMAO in the early diagnosis of CAD should be further explored.

Sex-Specific Perturbation of Systemic Lipidomic Profile in Newborn Lambs Impacted by Prenatal Testosterone Excess.

Gestational hyperandrogenism adversely impacts offspring health. Using an ovine model, we found that prenatal testosterone (T) excess adversely affects growth and cardiometabolic outcomes in female offspring and produces sex-specific effects on fetal myocardium. Since lipids are essential to cardiometabolic function, we hypothesized that prenatal T excess leads to sex-specific disruptions in lipid metabolism at birth. Shotgun lipidomics was performed on the plasma samples collected 48 hours after birth from female (F) and male (M) lambs of control (C) and (T) sheep (CF = 4, TF = 7, CM = 5, TM = 10) and data were analyzed by univariate analysis, multivariate dimensionality reduction modeling followed by functional enrichment, and pathway analyses. Biosynthesis of phosphatidylserine was the major pathway responsible for sex differences in controls. Unsupervised and supervised models showed separation between C and T in both sexes with glycerophospholipids and glycerolipids classes being responsible for the sex differences between C and T. T excess increased cholesterol in females while decreasing phosphatidylcholine levels in male lambs. Specifically, T excess: 1) suppressed the phosphatidylethanolamine N-methyltransferase (PEMT) phosphatidylcholine synthesis pathway overall and in TM lambs as opposed to suppression of carnitine levels overall and TF lambs; and 2) activated biosynthesis of ether-linked (O-)phosphatidylethanolamine and O-phosphatidylcholine from O-diacylglycerol overall and in TF lambs. Higher cholesterol levels could underlie adverse cardiometabolic outcomes in TF lambs, whereas suppressed PEMT pathway in TM lambs could lead to endoplasmic reticulum stress and defective lipid transport. These novel findings point to sex-specific effects of prenatal T excess on lipid metabolism in newborn lambs, a precocial ovine model of translational relevance.

Development of a blood‐based biomarker signature for detection of cognitive impairment through a targeted metabolomics approach deciphering the association with depression

AbstractBackgroundA series of pathological episodes set off the development of cognitive impairment, which precede years before the onset of clinical symptoms. Disrupted glucose and fatty acid metabolism notably contributes to the development of cognitive impairment and further advancement to clinical dementia. Disrupted metabolism leads to the secretion of various inflammatory eicosanoids leading to neuroinflammation. Alteration of some specific metabolites in plasma are noted during these metabolic changes. Depression is a key risk factor of cognitive impairment, and similar changes in plasma metabolites have observed in the pathophysiology of depression. This aim of this project is to establish a blood‐based biomarker signature for early detection of cognitive impairment in individuals with depression through quantifying plasma levels of metabolites associated with glucose and fatty acid metabolism in plasma samples from the participants of the Sydney Memory and Ageing Study (MAS).MethodSamples of 275 participants were randomly collected from baseline and 251 from an 8 year follow up study. At baseline there were 130 healthy participants, 93 participants with MCI, 36 participants with depression and 16 participants had both MCI and depression. Plasma samples were analysed to quantify the levels of fatty acids and carnitines using chemical derivatization – UPLC‐MRM/MS.ResultSignificant correlations were observed between the biomarkers like FA040 butyric acid (P: 0.034), FA224 (P: 0.032), acotinic acid (P:0.027) with MMSE. Biomarkers like C70carnitine (P:0.010), C90carnitine (P: 0.033), C150carnitine (P: 0.016), C160 carnitines (P: 0.004) significantly correlated with GDS scales. Linear regression showed significance between C90 carnitine (P: 0.021; β: 0.139) ad GDS scale. Whereas linear regression showed significant relationship between FA224 (P: 040, β: ‐.122), acotinic acid (P: 0.042, β: ‐.122), FA040 butyric acid (P: 0.036, β: ‐.193) with MMSE indicative of cognitive impairment.ConclusionThe study will help to identify candidate metabolites of perturbed fatty acid metabolism and establish a plasma biomarker signature of early cognitive impairment, by deciphering the association with depression as a risk factor. An association will be established between central AD pathology and peripheral metabolic changes, and potential treatment options targeting the right biochemical pathways will be identified.

Assessment of Serum Carnitine level in Children with Iron Deficiency Anemia

Assessment of Serum Carnitine level in Children with Iron Deficiency Anemia

Unveiling Disrupted Lipid Metabolism in Benign Prostate Hyperplasia, Prostate Cancer, and Metastatic Patients: Insights from a Colombian Nested Case-Control Study.

Prostate cancer is a significant global health concern, and its prevalence is increasing worldwide. Despite extensive research efforts, the complexity of the disease remains challenging with respect to fully understanding it. Metabolomics has emerged as a powerful approach to understanding prostate cancer by assessing comprehensive metabolite profiles in biological samples. In this study, metabolic profiles of patients with benign prostatic hyperplasia (BPH), prostate cancer (PCa), and metastatic prostate cancer (Met) were characterized using an untargeted approach that included metabolomics and lipidomics via liquid chromatography and gas chromatography coupled with high-resolution mass spectrometry. Comparative analysis among these groups revealed distinct metabolic profiles, primarily associated with lipid biosynthetic pathways, such as biosynthesis of unsaturated fatty acids, fatty acid degradation and elongation, and sphingolipid and linoleic acid metabolism. PCa patients showed lower levels of amino acids, glycerolipids, glycerophospholipids, sphingolipids, and carnitines compared to BPH patients. Compared to Met patients, PCa patients had reduced metabolites in the glycerolipid, glycerophospholipid, and sphingolipid groups, along with increased amino acids and carbohydrates. These altered metabolic profiles provide insights into the underlying pathways of prostate cancer's progression, potentially aiding the development of new diagnostic, and therapeutic strategies.

Evaluation of free and bound carnitine in young athletes

The study of the characteristics of carnitine metabolism in representatives of certain sports makes it possible to study the effect of physical loads of various nature on the body of a young athlete, and also makes it possible to assess the competitive potential and predict the tolerance of long-term and intense loads. Purpose. This study is to investigate the characteristics of carnitine metabolism in young athletes of various specializations. Material and methods. The study included athletes aged 14 to 18 who had been engaged in intense physical exercise for at least 12 hours per week forthe past 12 months or more. The control group consisted of healthy children aged 14 to 18 who were not involved in sports. In the blood serum of all study participants, the concentration of free carnitine, acetylcarnitine and acylcarnitines was determined. Based on the data obtained, ratios were calculated reflecting the activity of lipid beta-oxidation enzymes. Results. We found that the content of free carnitine in the representatives of all the studied groups was within the normal range. At the same time, the level of free carnitine in the blood of athletes involved in field hockey was significantly lower than that of athletes-swimmers and representatives of the control group (p&lt;0.001). It was also studied that, compared with athletes-swimmers and the control group, athletes-hockey players have significantly higher functional activity of carnitine palmitoyltransferase 1 (p&lt;0.05) and lipid beta-oxidation enzymes (p&lt;0.001). Conclusion. In our work we have demonstrated that athletes involved in team sports (field hockey) have a more pronounced shift towards fatty acid oxidation compared to aerobic sports (swimming). A possible reason for the identified changes may be a more significant effect of alternating aerobic and anaerobic loads on lipid metabolism compared to exclusively aerobic activity.