Total Carnitine Concentrations Research Articles

Is hyperammonemia helpful in detecting syndromic tubulopathies with early extrarenal manifestations? A case report of Lowe’s syndrome

BackgroundGenerally, it is not well known that Lowe’s syndrome may coexist with hyperammonemia and hipocarnitynemia. The importance of hyperammonemia in the diagnosis of kidney diseases is not completely understood.Case presentationWe present the history of a 13-year-old boy, admitted to the hospital due to proteinuria. In the past, the boy was diagnosed with binocular cataracts in infancy. Then he went through neurological diagnostic tests which diagnosed muscular hypotonia and psychomotor retardation but no inherited errors of metabolism were found. Proteinuria has been observed since the age of 2. Ultrasound imaging at the age of 5 showed the presence of a shading deposit in the kidney. At the age of 13, the boy was referred to the Pediatric Nephrology Ward. The laboratory tests revealed: a reduction of glomerular filtration rate, metabolic acidosis, proteinuria, hypercalciuria, increased activity of AST (SGOT), CK, LDH, hyperammonemia, and decreased concentration of total carnitine in blood serum. Based on the clinical presentation, Lowe’s syndrome was diagnosed. The genetic testing revealed an OCRL gene hemizygous mutation.ConclusionLowe’s syndrome is an example of a disease in which clinical symptoms—although occurring early and in high intensity—may not raise the suspicion of tubulopathy for a long time if they are not analyzed in a complex manner. There is a necessity to educate healthcare practitioners from other fields about the extrarenal symptoms of genetically determined tubulopathies.l-carnitine deficiency may be a symptom of proximal tubulopathy, including Lowe’s syndrome. l-carnitine deficiency leads to disturbances in the efficiency of the urea cycle, which results in hyperammonemia. Hyperammonemia is not only a symptom of inborn errors of metabolism and liver failure, but it may also lead to the diagnosis of tubulopathy.Since carnitine supplementation could have the desired beneficial effect on the patient’s general condition, it is postulated to conduct further studies on larger groups of patients with Lowe’s syndrome.

Excess Dietary Lysine Increases Skeletal Muscle and Plasma Trimethyllysine in Rats

Trimethyllysine, a carnitine precursor, is a cation. This study was designed to determine whether dietary potassium and lysine concentration or oral lysine supplementation affects tissue carnitine and trimethyllysine concentration in rats. In Experiment 1, rats were fed a control diet, a low or high potassium diet, or a high lysine diet. In Experiment 2, rats were given by gavage a solution containing either L-proline (control) or L-lysine. In Experiment 1, rats fed the high lysine diet had significantly lower plasma total carnitine concentration than controls. Rats fed the high lysine diets had significantly higher concentrations of free trimethyllysine in skeletal muscle and plasma relative to control rats and rats fed the high potassium diet. Rats fed the low potassium diet had a similar increase in skeletal muscle free trimethyllysine. In Experiment 2, rats given lysine had significantly lower plasma total carnitine concentration, and significantly greater skeletal muscle and plasma trimethyllysine concentration relative to controls. We conclude that dietary potassium and lysine, and oral lysine, have a significant effect upon the distribution of carnitine and trimethyllysine in rats. The distributional changes caused by lysine, however, seem to be due to effects other than exchange of lysine for carnitine or trimethyllysine in tissues.

Twenty-Four Weeks of L-Carnitine Combined with Leucine Supplementation Does Not Increase the Muscle Carnitine Content in Healthy Active Subjects

Introduction: To increase the total carnitine (TC) content in muscles, L-carnitine (LC) should be co-ingested with carbohydrates to induce an insulin response. Leucine has an insulin secretagogue effect. Therefore, the primary aim of this study was to examine the effects of 24 weeks of LC and leucine supplementation on the skeletal muscle TC content, muscle mass, and strength in active college-aged subjects. The secondary aim was to determine the activation of the Akt/mTOR signaling pathway in skeletal muscles after supplementation. Methods: Over the 24 weeks, the participants were supplemented with either 1 g of LC-L-tartrate and 3 g of leucine per day (LC + L group; n = 7) or 4 g of leucine per day (L group; n = 7) as a placebo. Before and 24 weeks after the initiation of the study protocol, the free carnitine (FC) and TC content in plasma and muscle samples, as well as body composition and muscle strength, were measured. In addition, the phosphorylation of the Akt/mTOR pathway proteins in muscles was evaluated. Results: Plasma FC and TC content increased in LC + L group after 24 weeks of supplementation (p = 0.003 and 0.010, respectively). However, the skeletal muscle FC and TC contents were not affected by the supplementation protocol. No changes were noted in the body mass and composition; serum insulin-like growth factor-1 concentration; and phosphorylation of the signaling pathway proteins Akt, mTOR, and p70S6K. Conclusion: LC supplementation may have the potential to exert beneficial effects in muscle atrophy. Therefore, additional research is necessary to investigate the effect of various LC supplementation protocols.

Exploring the functional and metabolic effects of adding garra fish meal to a plant-based broiler chicken diet.

The present study evaluated the metabolic and functional effects of adding garra meal to a broiler chicken diet. Three hundred twenty Sasso-breed day-old chicks were randomly assigned to four dietary treatments with either 0, 10, 20 or 30% garra meal added on top of formulated starter and grower basal diets. The experiment lasted for 42days. Feed intake and body weight gain increased at the starter and grower phases of broilers with garra meal addition (P < 0.05). Broiler chickens fed 30% garra meal were more efficient in converting feed to body weight and yielded the highest carcass weight (P < 0.05). Crude protein ileal digestibility coefficient was higher with 20% (76.2%), and crude fat with 20 (92.1) and 30% (92.6%) garra meal receiving groups (P < 0.05). The increase in individual and total esterified carnitine concentrations in dried blood spots demonstrated the elevated metabolic rate with garra meal addition (P < 0.05). A better supply of glucogenic substrate to the citric acid cycle was seen with garra meal addition due to the increase of propionylcarnitine to acetylcarnitine ratio (P < 0.05) without any apparent effect on ketogenesis in terms of serum 3-hydroxybutyrylcarnitine to acetylcarnitine ratio. Yet, it likely showed that part of the amino acids from garra meal were used as glucogenic substrate (P < 0.05). Histomorphometry data showed 20% garra meal addition elevated villus height, crypt depth and their ratio in the proximal parts of the small intestine (duodenum and jejunum) with the opposite results observed in the more distal part (ileum) with the highest for the control group (P < 0.05). It can be concluded that garra meal improved broiler performance when added to a plant-based diet and only few parameters warranted for caution when using more up to 30% garra meal addition. Beyond growth performance, garra meal generated a shift to a more efficient digestion, absorption and nutrient metabolism.

Increasing skeletal muscle carnitine content in older individuals increases whole-body fat oxidation during moderate-intensity exercise.

Intramyocellular lipid (IMCL) utilization is impaired in older individuals, and IMCL accumulation is associated with insulin resistance. We hypothesized that increasing muscle total carnitine content in older men would increase fat oxidation and IMCL utilization during exercise, and improve insulin sensitivity. Fourteen healthy older men (69 ± 1 year, BMI 26.5 ± 0.8 kg/m2) performed 1 h of cycling at 50% VO2max and, on a separate occasion, underwent a 60 mU/m2/min euglycaemic hyperinsulinaemic clamp before and after 25 weeks of daily ingestion of a 220 ml insulinogenic beverage (44.4 g carbohydrate, 13.8 g protein) containing 4.5 g placebo (n = 7) or L‐carnitine L‐tartrate (n = 7). During supplementation, participants performed twice‐weekly cycling for 1 h at 50% VO2max. Placebo ingestion had no effect on muscle carnitine content or total fat oxidation during exercise at 50% VO2max. L‐carnitine supplementation resulted in a 20% increase in muscle total carnitine content (20.1 ± 1.2 to 23.9 ± 1.7 mmol/kg/dm; p < 0.01) and a 20% increase in total fat oxidation (181.1 ± 15.0 to 220.4 ± 19.6 J/kg lbm/min; p < 0.01), predominantly due to increased IMCL utilization. These changes were associated with increased expression of genes involved in fat metabolism (ACAT1, DGKD & PLIN2; p < 0.05). There was no change in resting insulin‐stimulated whole‐body or skeletal muscle glucose disposal after supplementation. This is the first study to demonstrate that a carnitine‐mediated increase in fat oxidation is achievable in older individuals. This warrants further investigation given reduced lipid turnover is associated with poor metabolic health in older adults.

Carnitine chloride reduces the severity of experimental hyperhomocysteinemia and promotes lactate utilization by mitochondrial fraction of the rat epididymis

Hyperhomocysteinemia is a risk factor for many diseases, including reproductive disorders in men. L-carnitine is used in medical practice to correct impaired bioenergetic conditions; in patients with idiopathic forms of infertility its effects are associated with improvement of the sperm parameters. However, the effect of exogenous L-carnitine on the level of homocysteine in the gonadal tissues, as a risk factor for impaired fertility, has not been investigated yet. The aim of this study was to investigate activity of bioenergetic enzymes in the epididymal mitochondrial fraction, the dynamics of changes in the cytoplasmic and mitochondrial lactate levels and LDH activity, the total carnitine content, as well as the oxidative status of these cells under conditions of oxidative stress caused by hyperhomocysteinemia, and to assess the effect of carnitine chloride on these parameters under conditions of methionine administration to male Wistar rats. Methionine administration to animals for three weeks at a dose of 3 g/kg, resulted in development of the severe forms of hyperhomocysteinemia with serum homocysteine concentrations exceeding 100 μmol/L. This was accompanied by a decrease in the activity of enzymes involved in the bioenergetic processes of the cell: tissue respiration (succinate dehydrogenase) and oxidative phosphorylation (H+-ATPase) in the epididymal head and tail. The change in lactate metabolism included an increase in its level in both the mitochondrial and cytoplasmic fractions of the epididymal head and mitochondria of the epididymal tail, and also simultaneous statistically significant decrease in LDH activity in the mitochondria and cytoplasm of the epididymal head. In male rats with severe hyperhomocysteinemia, an increase in the activity of mitochondrial SOD accompanied by an increase in the carbonylation of mitochondrial proteins in the head and tail of the epididymis was noted. Modeling of hyperhomocysteinemia under conditions of carnitine chloride of administration led to different reactions of the cells of the studied tissues assayed in the epididymal head and tail homogenate. In the epididymal head, carnitine chloride promoted an increase in the mitochondrial lactate concentration and a decrease in the cytoplasmic lactate concentration, as well as an increase in the LDH activity associated with the mitochondrial fraction. These changes were accompanied by an increase in the activity of H+-ATPase in the epididymal, thus suggesting that carnitine chloride stimulated lactate transport of into the mitochondria and its use as an energy substrate under conditions of oxidative stress caused by hyperhomocysteinemia. In the tail tissues, the changes were protective in nature and were associated with a decrease in the formation of oxidatively modified proteins.

Carnitine status before and after paracentesis in patients with ascites and liver cirrhosis and improvement of subjective symptoms by intravenous administration of carnitine ― Initial study

Carnitine status before and after paracentesis in patients with ascites and liver cirrhosis and improvement of subjective symptoms by intravenous administration of carnitine ― Initial study

Disorders of carnitine metabolism in premature infants with fan-associated pneumonia

We studied the concentration of carnitine and its fractions in peripheral blood in 22 premature infants with fan-associated pneumonia and in 20 conditionally healthy premature infants by tandem mass spectrometry. The birth body weight of children was 2,086.32 ± 117.13 and 2,140.9 ± 74.4 g, gestational age was 33.7 ± 0.41 and 34.16 ± 0.51 weeks, respectively. The concentration of total carnitine was at the lower limit or decreased in 10 (45%) children in the acute period of the disease. 4 newborns with fan-associated pneumonia demonstrated persistent carnitine deficiency: the content of free carnitine was very low: 7.47 – 8, 37 μmol/l (7.97 ± 0.197 μmol/l), the concentration of total carnitine was also reduced (21.55 – 22.01 μmol/l, 21.7 ± 0.366 μmol/l). The fractions of acylcarnitines varied widely throughout the disease. One child had high rates of C18OH (0.282 μmol/l; norm 0–0.110 μmol/l) and C18:1OH (0.282 μmol/l; norm 0–0.180 μmol/l) during the entire neonatal period. It could be associated with mitochondrial trifunctional protein deficiency. The study of total carnitine and its fractions in premature infants with fan-associated pneumonia allowed us to identify violations of its metabolism, both secondary and hereditary at early stage.

Lactational Responses of Heat-Stressed Dairy Goats to Dietary L-Carnitine Supplementation.

Simple SummaryEndogenous carnitine synthesis is reduced by heat stress, and we hypothesized that carnitine supplementation would improve lipid metabolism and performance of dairy goats when exposed to high ambient temperature. In the current study, goats were exposed to thermal-neutral (15 to 20 °C) or heat stress (28 to 35 °C) conditions. In each environmental condition, goats were supplemented or not with rumen-protected carnitine in their diets. Goats exposed to heat stress experienced high body temperatures and respiratory rates, and reduced feed intake and milk production. Carnitine supplementation was transferred efficiently to blood, but had no effect on physiological or productive parameters in goats. We conclude that extra carnitine has no beneficial effects on goats’ performance and is not needed in thermal-neutral or heat stress conditions. Heat stress causes significant losses in milk production, and nutritional strategies are needed to alleviate its effects. Endogenous carnitine synthesis is also reduced by heat stress (HS). Carnitine plays a central role in fatty acid oxidation and buffers the toxic effects of acyl groups. We hypothesized that carnitine supplementation would make up for any carnitine deficiencies during HS and improve lipid metabolism. The objective was to evaluate rumen-protected L-carnitine (CAR) supplementation in dairy goats under thermo-neutral (TN) or HS conditions. Four Murciano-Granadina dairy goats were used in a four × four Latin square design. Goats were allocated to one of four treatments in a two × two factorial arrangement. Factors were 1) diet: control (CON) or supplementation with CAR (1 g/d); and 2) ambient conditions: TN (15 to 20 °C) or HS (0900 to 2100 h at 35 °C, 2100 to 0900 h at 28 °C). Blood free-, acetyl-, and total-carnitine concentrations increased almost three times by supplementation. Despite this efficient absorption, CAR had no effect on feed intake, milk production or blood metabolites in TN or HS conditions. Heat stress increased rectal temperature and respiratory rate. Additionally, HS goats experienced 26% loss in feed intake, but they tended to eat longer particle sizes. Compared to TN, heat-stressed goats lost more subcutaneous fat (difference in fat thickness measured before and after each period = −0.72 vs. +0.64 mm). In conclusion, supplemented L-carnitine was efficiently absorbed, but it had no lactational effects on performance of goats under thermo-neutral or heat stress conditions.

Effects of l-carnitine administration on health-related quality of life during cisplatin-based chemoradiotherapy in patients with head and neck squamous cell carcinoma

ObjectivesCancer-related fatigue impairs daily functioning and negatively impacts health-related quality of life (HRQoL). Our previous study revealed that cisplatin-based chemoradiotherapy (CRT) impairs the carnitine system and carnitine deficiency leads to poor physical functioning. This open label, randomized, controlled prospective study investigated the effects of l-carnitine administration on plasma carnitine concentration, CRT-induced fatigue, and decline in HRQoL in patients with head and neck squamous cell carcinoma (HNSCC). MethodsPatients were divided into experimental group (received 1000mg of oral liquid l-carnitine once daily for 8 weeks) and control group. The primary and secondary endpoints were the change in HRQoL scores and the change in carnitine levels, respectively, from baseline (pre-CRT) to after CRT. ResultsThe mean total plasma carnitine concentration in the control group decreased significantly, 2 weeks after the end of chemotherapy, while no significant differences were seen in the l-carnitine group. l-carnitine administration, therefore, kept the physical functioning score unchanged. ConclusionOur study shows that patients who receive CRT experience chemotherapy-induced damage of carnitine homeostasis leading to deficiency of carnitine and impairment of HRQoL. l-carnitine administration is beneficial in improving the HRQoL in patients with HNSCC.

Efecto del nivel de complementación con Metionina-Colina en vacas Holstein durante el periodo de transición sobre las concentraciones hepáticas de triglicéridos, colina y carnitina

Con el objetivo de evaluar el potencial lipotrópico de metionina-colina en vacas lecheras durante el periodo de transición, dosis de 20 g/d de una Fuente Comercial Protegida de la Degradación Ruminal (FCPDR) de metionina, y sus combinaciones con una FCPDR de colina en dosis de 60 y 120 g/d fueron suministradas a vacas entre el día 260 de gestación y el día 20 posparto. Estas pastoreaban kikuyo (Cenchrus clamdestinum) y recibieron un complemento alimenticio. El día 270 de gestación y a los días 10 y 20 posparto se cuantificaron las concentraciones plasmáticas de Ácidos Grasos No Esterificados (AGNES), β-Hidroxibutirato (BHB) y Triglicéridos (TG), así como las concentraciones hepáticas de triacilglicéridos, de colina, carnitina total, carnitina libre y acil carnitina. Durante el preparto se presentaron los valores significativamente más altos (p &lt; 0.05) de TG plasmáticos y los valores significativamente más bajos (p &lt; 0.05) de AGNES y BHB. Las concentraciones hepáticas de TG, de colina y de las diferentes formas de carnitina no difirieron significativamente entre periodos de muestreo y no se vieron afectadas por la suplementación con metionina-colina. Las concentraciones plasmáticas de BHB aumentaron significativamente (p &lt; 0.05) con la suplementación conjunta con metionina y colina, sugiriendo un aumento en la oxidación de ácidos grasos. Se concluye que con concentraciones bajas de AGNES, la metionina y colina no son nutrientes limitantes para la exportación de TG desde el hígado a la sangre. Bajo esta condición no se observó lipidosis hepática y como consecuencia la suplementación con metionina-colina no ocasionó efectos significativos sobre las concentraciones hepáticas de TG.

Hyperammonemia in a Child Presenting with Growth Delay, Short Stature, and Diarrhea

A 5-year-old male child was referred to the metabolism clinic with a history of failure to thrive, chronic intermittent emesis, diarrhea, seizures, hypotonia, and growth hormone deficiency. He was also noted to experience frequent falling episodes. Routine biochemistry testing revealed increased plasma ammonia concentration at 184 μmol/L (reference interval, 16–47) and lactate dehydrogenase concentration at 445 U/L (reference interval, 110–295). Plasma free and total carnitine concentrations were decreased at 5 μmol/L (reference interval, 26–60) and 17.1 μmol/L (reference interval, 32–84), respectively. Orotic acid excretion in urine was also markedly increased at >80 mmol/mol creatinine (reference interval, 0.2–1.5). Plasma insulin-like growth factor-I (IGF-I)4 concentration was also decreased at <25 ng/mL (reference interval, 50–286). Paired plasma and urine specimens were collected for amino acid analysis using ultraperformance liquid chromatography. The results are shown in Table 1. View this table: Table 1. Amino acid analysis of paired plasma and urine. This patient has lysinuric protein intolerance (LPI), an autosomal recessive disorder of amino acid transport, caused by mutations in the solute carrier family 7, member 7 ( SLC7A7 ) gene (1, 2, 3). Although the worldwide incidence is not known, LPI is estimated to occur in approximately 1 in 60000 newborns in Finland and Japan (2). The SLC7A7 gene product is the …

Oxidative effect of l-carnitine on energy metabolism in diploid and triploid rainbow trout (Oncorhynchus mykiss): impact on metabolites

l-Carnitine plays a key role in the regulation of energy metabolism and growth in fish. The aim of this study was to determine the effects of dietary l-carnitine levels on carnitine homeostasis and energy metabolism in diploid and triploid trout (Oncorhynchus mykiss). Diploid and triploid trout (29.5 ± 0.6 and 31.8 ± 0.5 g, respectively) were fed with three diets supplemented with 15, 200 or 530 mg l-carnitine/kg, respectively, for 56 days. Compared to 15 mg l-carnitine, total carnitine content increased in the liver by 182% in diploid and by 154% in triploid trout fed 530 mg l-carnitine. In muscle, total carnitine content increased by 60 and 73% in diploid and by 34 and 75% in triploid with the increase in dietary l-carnitine levels. l-Carnitine caused no significant change in the plasma concentrations of metabolites like proteins (ammonia, urea and protein), lipid (triglycerides), carbohydrate (glucose, lactate) and enzyme activities (lipase, lactate, alanine transaminase, lactic acid dehydrogenase). Triploid trout had significantly lower plasma ammonia (P = 0.003), lipase (P = 0.005) and triiodothyronine (T3; P = 0.003) levels than diploid trout. In conclusion, ploidy significantly affected the energy metabolism in rainbow trout, dietary l-carnitine levels altered the l-carnitine homeostasis, but not influence nutritional metabolism.

The carnitine status does not affect the contractile and metabolic phenotype of skeletal muscle in pigs

BackgroundRecently, supplementation of L-carnitine to obese rats was found to improve the carnitine status and to counteract an obesity-induced muscle fiber transition from type I to type II. However, it has not been resolved if the change of muscle fiber distribution induced in obese rats and the restoration of the “normal” muscle fiber distribution, which is found in lean rats, in obese rats by supplemental L-carnitine is causally linked with the carnitine status. In the present study we hypothesized that fiber type distribution in skeletal muscle is dependent on carnitine status.MethodsTo test this, an experiment with 48 piglets which were randomly allocated to four groups (n = 12) was performed. All piglets were given orally either 60 mg sodium bicarbonate/kg body weight (group CON), 20 mg L-carnitine and 60 mg sodium bicarbonate/kg body weight (group CARN), 30 mg pivalate (dissolved in sodium bicarbonate)/kg body weight (group PIV) or 20 mg L-carnitine and 30 mg pivalate/kg body weight (group CARN + PIV) each day for a period of 4 weeks.ResultsConcentrations of total carnitine in plasma, liver and longissimus dorsi and biceps femoris muscles were 2.0–2.7 fold higher in group CARN than in group CON, whereas these concentrations were 1.9–2.5-fold lower in group PIV than in group CON. The concentrations of total carnitine in these tissues did not statistically differ between group CARN + PIV and group CON. Fiber type distribution of longissimus dorsi and biceps femoris muscles, mRNA and protein levels of molecular regulators of fiber distribution in longissimus dorsi and biceps femoris muscles and mRNA levels of genes reflecting the metabolic phenotype of longissimus dorsi and biceps femoris muscles did not differ between groups.ConclusionChanges in the systemic carnitine status and the muscle carnitine concentration induced by either supplementing L-carnitine or administering pivalate have no impact on the contractile and metabolic phenotype of skeletal muscles in pigs.

Muscle carnitine availability plays a central role in regulating fuel metabolism in the rodent.

Meldonium inhibits endogenous carnitine synthesis and tissue uptake, and accelerates urinary carnitine excretion, although the impact of meldonium-mediated muscle carnitine depletion on whole-body fuel selection, and muscle fuel metabolism and its molecular regulation is under-investigated. Ten days of oral meldonium administration did not impact on food or fluid intake, physical activity levels or body weight gain in the rat, whereas it depleted muscle carnitine content (all moieties), increased whole-body carbohydrate oxidation and muscle and liver glycogen utilization, and reduced whole-body fat oxidation. Meldonium reduced carnitine transporter protein expression across muscles of different contractile and metabolic phenotypes. A TaqMan PCR low-density array card approach revealed the abundance of 189 mRNAs regulating fuel selection was altered in soleus muscle by meldonium, highlighting the modulation of discrete cellular functions and metabolic pathways. These novel findings strongly support the premise that muscle carnitine availability is a primary regulator of fuel selection invivo. The body carnitine pool is primarily confined to skeletal muscle, where it regulates carbohydrate (CHO) and fat usage. Meldonium (3-(2,2,2-trimethylhydrazinium)-propionate) inhibits carnitine synthesis and tissue uptake, although the impact of carnitine depletion on whole-body fuel selection, muscle fuel metabolism and its molecular regulation is under-investigated. Male lean Zucker rats received water (control, n=8) or meldonium-supplemented water (meldonium, n=8) for 10days [1.6gkg-1 body mass (BM)day-1 days 1-2, 0.8gkg-1 BMday-1 thereafter]. From days 7-10, animals were housed in indirect calorimetry chambers after which soleus muscle and liver were harvested. Food and fluid intake, weight gain and physical activity levels were similar between groups from days 7 to 10. Compared to control, meldonium depleted muscle total carnitine (P<0.001) and all carnitine esters. Furthermore, whole-body fat oxidation was less (P<0.001) and CHO oxidation was greater (P<0.05) compared to the control, whereas soleus and liver glycogen contents were less (P<0.01 and P<0.01, respectively). In a second study, male Wistar rats received water (n=8) or meldonium-supplemented water (n=8) as above, and kidney, heart and extensor digitorum longus muscle (EDL) and soleus muscles were collected. Compared to control, meldonium depleted total carnitine content (all P<0.001), reduced carnitine transporter protein and glycogen content, and increased pyruvate dehydrogenase kinase 4 mRNA abundance in the heart, EDL and soleus. In total, 189 mRNAs regulating fuel selection were differentially expressed in soleus in meldonium vs. control, and a number of cellular functions and pathways strongly associated with carnitine depletion were identified. Collectively, these data firmly support the premise that muscle carnitine availability is a primary regulator of fuel selection invivo.

Systemic regulation of L-carnitine in nutritional metabolism in zebrafish, Danio rerio

Excess fat accumulation has been observed widely in farmed fish; therefore, efficient lipid-lowering factors have obtained high attention in the current fish nutrition studies. Dietary L-carnitine can increase fatty acid β-oxidation in mammals, but has produced contradictory results in different fish species. To date, the mechanisms of metabolic regulation of L-carnitine in fish have not been fully determined. The present study used zebrafish to investigate the systemic regulation of nutrient metabolism by dietary L-carnitine supplementation. L-carnitine significantly decreased the lipid content in liver and muscle, accompanied by increased concentrations of total and free carnitine in tissues. Meanwhile, L-carnitine enhanced mitochondrial β-oxidation activities and the expression of carnitine palmitoyltransferase 1 mRNA significantly, whereas it depressed the mRNA expression of adipogenesis-related genes. In addition, L-carnitine caused higher glycogen deposition in the fasting state, and increased and decreased the mRNA expressions of gluconeogenesis-related and glycolysis-related genes, respectively. L-carnitine also increased the hepatic expression of mTOR in the feeding state. Taken together, dietary L-carnitine supplementation decreased lipid deposition by increasing mitochondrial fatty acid β-oxidation, and is likely to promote protein synthesis. However, the L-carnitine-enhanced lipid catabolism would cause a decrease in glucose utilization. Therefore, L-carnitine has comprehensive effects on nutrient metabolism in fish.

Relationship of Serum Carnitine Level with Falls and Gait Disturbance in the Elderly.

Gait disturbance and falls are serious events that can impair activities of daily living (ADL) in the elderly. On the other hand, carnitine plays essential roles in energy production, and carnitine deficiency leads to low activity levels. We examined whether a lower serum carnitine concentration was correlated with falls and gait disturbances in the elderly. We performed a cross-sectional study. One hundred and ninety-eight elderly patients (male, 83; female, 115; 81 ± 6 years old) were enrolled in this study. Physical performance (hand grip strength, leg strength, walking speed, one-leg standing time, and tandem gait steps) and frailty status (The Edmonton Frail Scale: EFS) were evaluated. The serum total, free, and acylated carnitine levels were measured using an enzyme cycling method. We then investigated the associations between the serum carnitine level, history of falls, and the results of these physical examinations. Of the 198 subjects, 56 (28%) had a history of falls within the past one year. The patients with a history of falls had lower serum total carnitine and free carnitine levels than those without a history of falls. Regarding the physical performance results, the patients with a history of falls had higher EFS scores, a weaker hand grip strength, a slower walking speed, a shorter one-leg standing time, and a smaller number of tandem gait steps than those without a history of falls. A logistic regression analysis showed that the low serum total carnitine concentration was identified as an independent factor associated with a history of falls, a slow walking speed after adjustments for age, sex and modified EFS. A low serum carnitine level is associated with a history of falls and gait disturbances in elderly people.

Age in days-related variations in neonatal blood carnitine concentrations and its clinical significance

Objective To investigate the relationship between neonatal blood carnitine levels and the factors of gender, days after birth gestational age (GA) and birth weight (BW), and to provide some data for routine neonatal metabolic screening. Methods A total of 490 neonates from Department of Neonatology, the Sixth Affiliated Hospital of Sun Yat-Sen University and Women and Children′s Hospital of Sanshui District, Foshan during the period July 2012 to December 2015 were recruited in this study.They were divided into 3 groups according to days after birth, within 1 day after birth for group A (207 cases), 2-3 days for group B (153 cases), 4 to 14 days for group C (130 cases). Then heel peripheral blood were collected.Free carnitine(FC), total acylcarnitines (AC) and total carnitine (TC)concentrations were measured by using tandem mass spectrometry (MS-MS) and then tested for the association between the biomarkers and the factors of gender, days after birth, GA and BW. Results Concentrations of TC and AC tapered off from day 1 to day 14.Concentrations of TC, FC and AC were significantly higher in male-preterm-low birth weight infants compared with female-fullterm infants with normal birth weight infants in group A. The differences were statistically significant(all P 0.05). Conclusions Neonatal blood carnitine concentrations have negative relationship with age, GA and BW.Therefore, during routine neonatal metabolic screening, full consideration should be given to the factors which may have an important influence on the carnitine levels. Key words: Total carnitine; Free carnitine; Acylcarnitine; Infant, newborn

Carnitine dynamics and their effects on hyperammonemia in cirrhotic Japanese patients

Supplementation with levocarnitine preparations has been reported to improve hepatic encephalopathy, but no detailed investigations have addressed the dynamics of carnitine or its supplementation indication in cirrhosis patients. We studied carnitine dynamics in cirrhotic patients by measuring serum and liver tissue carnitine levels and tested the effects of levocarnitine supplementation on concurrent hyperammonemia. In a pilot cohort of seven patients with liver cirrhosis and five patients without cirrhosis, the serum and liver carnitine concentrations were measured. Then the serum carnitine fractions were analyzed in 70 liver cirrhosis patients. Among them, a levocarnitine preparation (1800mg/day) was supplemented orally for 3months in 27 patients with refractory hyperammonemia, and the effects were evaluated. A significant correlation was observed between serum and liver tissue carnitine concentrations (r = 0.69, P <0.05). The serum total carnitine concentration was 68.4 ± 4.7μmol/L, the free carnitine concentration was 53.2 ± 2.6μmol/L, and the acylcarnitine concentration was 13.2 ± 1.1μmol/L in 70 cirrhotic patients (reference values are 45-91, 36-74, 6-23μmol/L, respectively). There was no correlation between blood ammonia and serum carnitine concentrations. The serum carnitine concentration rose with levocarnitine supplementation, reaching steady state after 1month and, in parallel, refractory hyperammonemia was significantly improved. The cut-off level for a 20% decrease in blood ammonia was identified as 62.0μmol/L total carnitine concentration by receiver-operating characteristic curve analysis, with an area under the curve of 0.69. Serum carnitine concentrations were within standard levels in the majority of liver cirrhosis patients. In patients with concurrent hyperammonemia, the levocarnitine supplementation reduced blood ammonia levels.

CARNITINE CHLORIDE EFFECT ON FUNCTIONAL STATE OF MITOCHONDRIA IN CONDITIONS OF NITRIC OXIDE SYNTHESIS DEFICIT

Aim. To study the effect of carnitine chloride on functional state of mitochondria and endogenous carnitine content in conditions of L-NAME-induced decrease in nitric oxide synthesis (II). Materials and methods. Twenty four Wistar rats were divided into the following groups: the control group, the group with intraperitoneal introduction of L-NAME in the dose of 25 mg/kg for 7 days and the group receiving L-NAME by the analogous scheme against the background of introduction of carnitine chloride in the dose of 300 mg/kg for 21 days. The animals experienced the study of lactate dehydrogenase (LDG), succinate dehydrogenase (SDG), superoxide dismutase (SOD), lactate, nitric oxide (II), carnitine (total, free, bound) and nonetherified fatty acid concentrations in the rat cardiomyocyte mitochondria. Results. L-NAME in the dose of 25 mg/kg led to decrease in NO metabolite (by 21,5 %, p < 0,05) and lactate (by 56 %, p < 0,05) concentrations in myocardiocyte mitochondria; at the same time, it increased nonetherified fatty acid (by 290 %, p < 0,05) and total carnitine (by 162 %, p < 0,05) content as well as activity of all the three measured oxidoreductases in mitochondrial cardiac tissues as compared to the control animal indices (LDG by 160 %, p < 0,05; SDG by 109 %, p < 0,05; SOD by 133 %, p < 0,05). Preliminary introduction of carnitine chloride induced reliable significant growth of SDG (by 163 %, p < 0,05) and SOD (by 376 %, p < 0,05) activity, rise in NO metabolite (by 437 %, p < 0,05) and lactate (by 62 %, p < 0,05) concentrations, as well as to fall in fatty acid (37 %, p < 0,05) and total carnitine (by 35 %, p < 0,05) concentrations and LDG activity (by 50 %, p < 0,05). Conclusions. Preliminary administration of cortinine chloride in the dose of 300 mg/kg before introduction of L-NAME in the dose of 25 mg/kg normalizes carnitine homeostasis, prevents decrease in NO metabolite concentration, declines nonetherified fatty acid concentration and significantly elevates SOD and SDG activity in the rat cardiomyocyte mitochondria.