Carnitine Concentrations Research Articles

Plasma Acylcarnitines and Development of Metabolic Syndrome in a Middle‐Aged and Older Chinese Population

Incomplete fatty acid oxidation leads to accumulation of intermediates such as acylcarnitines. The aim of this study was to investigate associations of carnitine and acylcarnitines with development of metabolic syndrome (MetS) in a middle‐aged and older Chinese population. In 2005, 3289 participants, aged 50‐70 years, were recruited from Beijing and Shanghai, China, and were resurveyed in 2011. Concentrations of baseline plasma free carnitine and acylcarnitines were quantified using liquid chromatography‐tandem mass spectrometry. After 6‐year follow up, 421 out of 1208 participants without MetS at baseline developed MetS. Free carnitine, propionylcarnitine, valerylcarnitine, octanenoylcarnitine, palmitoylcarnitine and 3‐Hydroxy‐octadecenoyl carnitine were each statistically significantly associated with incident MetS after correction for multiple testing. In a stepwise logistic regression including all of these (acyl)carnitines simultaneously, only free carnitine and octanenoylcarnitine remained significantly associated with incident MetS. Compared with those in the first quartile of free carnitine, those in the fourth quartile had 2 fold increased risk [odds ratio: 2.00, 95% confidence interval (CI): 1.40, 2.86] for incident MetS. Similar trend was observed for octanenoylcarnitine [OR, 95% CI: 2.21 (1.56, 3.14) comparing extreme quartiles]. In conclusion, accumulation of free carnitine and octanenoylcarnitine may increase the risk of MetS in middle‐aged and older Chinese adults.

Metabolic remodeling in moderate synchronous versus dyssynchronous pacing-induced heart failure: integrated metabolomics and proteomics study.

Heart failure (HF) is accompanied by complex alterations in myocardial energy metabolism. Up to 40% of HF patients have dyssynchronous ventricular contraction, which is an independent indicator of mortality. We hypothesized that electromechanical dyssynchrony significantly affects metabolic remodeling in the course of HF. We used a canine model of tachypacing-induced HF. Animals were paced at 200 bpm for 6 weeks either in the right atrium (synchronous HF, SHF) or in the right ventricle (dyssynchronous HF, DHF). We collected biopsies from left ventricular apex and performed comprehensive metabolic pathway analysis using multi-platform metabolomics (GC/MS; MS/MS; HPLC) and LC-MS/MS label-free proteomics. We found important differences in metabolic remodeling between SHF and DHF. As compared to Control, ATP, phosphocreatine (PCr), creatine, and PCr/ATP (prognostic indicator of mortality in HF patients) were all significantly reduced in DHF, but not SHF. In addition, the myocardial levels of carnitine (mitochondrial fatty acid carrier) and fatty acids (12:0, 14:0) were significantly reduced in DHF, but not SHF. Carnitine parmitoyltransferase I, a key regulatory enzyme of fatty acid ß-oxidation, was significantly upregulated in SHF but was not different in DHF, as compared to Control. Both SHF and DHF exhibited a reduction, but to a different degree, in creatine and the intermediates of glycolysis and the TCA cycle. In contrast to this, the enzymes of creatine kinase shuttle were upregulated, and the enzymes of glycolysis and the TCA cycle were predominantly upregulated or unchanged in both SHF and DHF. These data suggest a systemic mismatch between substrate supply and demand in pacing-induced HF. The energy deficit observed in DHF, but not in SHF, may be associated with a critical decrease in fatty acid delivery to the ß-oxidation pipeline, primarily due to a reduction in myocardial carnitine content.

Carnitine supplementation alleviates lipid metabolism derangements and protects against oxidative stress in non-obese hereditary hypertriglyceridemic rats.

The aim of this study was to estimate the effect of carnitine supplementation on lipid disorders and peripheral tissue insulin sensitivity in a non-obese animal model of insulin resistance, the hereditary hypertriglyceridemic (HHTg) rat. Male HHTg rats were fed a standard diet, and half of them received daily doses of carnitine (500 mg·kg(-1) body weight) for 8 weeks. Rats of the original Wistar strain were used for comparison. HHTg rats exhibited increased urinary excretion of free carnitine and reduced carnitine content in the liver and blood. Carnitine supplementation compensated for this shortage and promoted urinary excretion of acetylcarnitine without any signs of (acyl)carnitine accumulation in skeletal muscle. Compared with their untreated littermates, carnitine-treated HHTg rats exhibited lower weight gain, reduced liver steatosis, lower fasting triglyceridemia, and greater reduction of serum free fatty acid content after glucose load. Carnitine treatment was associated with increased mitochondrial biogenesis and oxidative capacity for fatty acids, amelioration of oxidative stress, and restored substrate switching in the liver. In skeletal muscle (diaphragm), carnitine supplementation was associated with significantly higher palmitate oxidation and a more favorable complete to incomplete oxidation products ratio. Carnitine supplementation further enhanced insulin sensitivity ex vivo. No effects on whole-body glucose tolerance were observed. Our data suggest that some metabolic syndrome-related disorders, particularly fatty acid oxidation, steatosis, and oxidative stress in the liver, could be attenuated by carnitine supplementation. The effect of carnitine could be explained, at least partly, by enhanced substrate oxidation and increased fatty acid transport from tissues in the form of short-chain acylcarnitines.

Effect of L-carnitine supplementation on the body carnitine pool, skeletal muscle energy metabolism and physical performance in male vegetarians.

More than 95% of the body carnitine is located in skeletal muscle, where it is essential for energy metabolism. Vegetarians ingest less carnitine and carnitine precursors and have lower plasma carnitine concentrations than omnivores. Principle aims of the current study were to assess the plasma and skeletal muscle carnitine content and physical performance of male vegetarians and matched omnivores under basal conditions and after L-carnitine supplementation. Sixteen vegetarians and eight omnivores participated in this interventional study with oral supplementation of 2 g L-carnitine for 12 weeks. Before carnitine supplementation, vegetarians had a 10% lower plasma carnitine concentration, but maintained skeletal muscle carnitine stores compared to omnivores. Skeletal muscle phosphocreatine, ATP, glycogen and lactate contents were also not different from omnivores. Maximal oxygen uptake (VO2max) and workload (P max) per bodyweight (bicycle spiroergometry) were not significantly different between vegetarians and omnivores. Sub-maximal exercise (75% VO2max for 1 h) revealed no significant differences between vegetarians and omnivores (respiratory exchange ratio, blood lactate and muscle metabolites). Supplementation with L-carnitine significantly increased the total plasma carnitine concentration (24% in omnivores, 31% in vegetarians) and the muscle carnitine content in vegetarians (13%). Despite this increase, P max and VO2max as well as muscle phosphocreatine, lactate and glycogen were not significantly affected by carnitine administration. Vegetarians have lower plasma carnitine concentrations, but maintained muscle carnitine stores compared to omnivores. Oral L-carnitine supplementation normalizes the plasma carnitine stores and slightly increases the skeletal muscle carnitine content in vegetarians, but without affecting muscle function and energy metabolism.

Abnormal Newborn Screening in a Healthy Infant of a Mother with Undiagnosed Medium-Chain Acyl-CoA Dehydrogenase Deficiency.

A neonate with low blood free carnitine level on newborn tandem mass spectrometry screening was evaluated for possible carnitine transporter defect (CTD). The plasma concentration of free carnitine was marginally reduced, and the concentrations of acylcarnitines (including C6, C8, and C10:1) were normal on confirmatory tests. Organic acids in urine were normal. In addition, none of the frequent Faroese SLC22A5 mutations (p.N32S, c.825-52G>A) which are common in the Danish population were identified. Evaluation of the mother showed low-normal free carnitine, but highly elevated medium-chain acylcarnitines (C6, C8, and C10:1) consistent with medium-chain acyl-CoA dehydrogenase deficiency (MCADD). The diagnosis was confirmed by the finding of homozygous presence of the c.985A>G mutation in ACADM.

Metabolic differentiation and classification of abnormal Savda Munziq's pharmacodynamic role on rat models with different diseases by nuclear magnetic resonance-based metabonomics.

Background:Abnormal Savda Munziq (ASMq) is a traditional Uyghur herbal preparation used as a therapy for abnormal Savda-related diseases. In this study, we investigate ASMq's dynamic effects on abnormal Savda rat models under different disease conditions.Materials and Methods:Abnormal Savda rat models with hepatocellular carcinoma (HCC), type 2 diabetes mellitus (T2DM), and asthma dosed of ASMq. Serum samples of each animal tested by nuclear magnetic resonance spectroscopy and analyzed by orthogonal projection to latent structure with discriminant analysis.Results:Compared with healthy controls, HCC rats had higher concentrations of amino acids, fat-related metabolites, lactate, myoinositol, and citrate, but lower concentrations of α-glucose, β-glucose, and glutamine. Following ASMq treatment, the serum acetone very low-density lipoprotein (VLDL), LDL, unsaturated lipids, acetylcysteine, and pyruvate concentration decreased, but α-glucose, β-glucose, and glutamine concentration increased (P < 0.05). T2DM rats had higher concentrations of α- and β-glucose, but lower concentrations of isoleucine, leucine, valine, glutamine, glycoprotein, lactate, tyrosine, creatine, alanine, carnitine, and phenylalanine. After ASMq treated T2DM groups showed reduced α- and β-glucose and increased creatine levels (P < 0.05). Asthma rats had higher acetate, carnitine, formate, and phenylalanine levels, but lower concentrations of glutamine, glycoprotein, lactate, VLDL, LDL, and unsaturated lipids. ASMq treatment showed increased glutamine and reduced carnitine, glycoprotein, formate, and phenylalanine levels (P < 0.05).Conclusion:Low immune function, decreased oxidative defense, liver function abnormalities, amino acid deficiencies, and energy metabolism disorders are common characteristics of abnormal Savda-related diseases. ASMq may improve the abnormal metabolism and immune function of rat models with different diseases combined abnormal Savda.

Carnitine Enigma: From Antioxidant Action to Vitagene Regulation. Part 2. Transcription Factors and Practical Applications

A growing interest has been shown in the potential uses of carnitine in medical practice and animal/poultry industry. The molecular mechanisms accounting for the positive effect of LC on livestock animals are not yet fully understood but many protective effects of LC in various stress conditions reported in literature, have been related to its antioxidant action. Based on the analysis of the recent publications presented in the review it could be concluded that antioxidant actions of carnitine are associated to much extent with redox signaling in the cell. Indeed, LC is shown to upregulate Nrf2 and PPARs and downregulates NF-κB leading to anti-apoptotic and anti-inflammation actions of carnitine. In fact, Nrf2-mediated synthesis of antioxidant enzymes, including SOD, GSH-Px, GR, GST and GSH, in response to carnitine supplementation could be a main driving force of antioxidant action of carnitine and its derivatives. Furthermore, LC and its derivatives are shown to affect vitagene networks resulting in increased adaptive ability to stresses via additional synthesis of protective molecules, including heat shock proteins (HO-1), upregulating sirtuins, thioredoxins and SOD. It seems likely that in biological system in vivo the interactions of the aforementioned mechanisms provide an important place for carnitine to be a crucial part of the integrated antioxidant systems of the animal and human body. Furthermore, direct scavenging ROS and chelating properties of carnitine would be very much relevant to the antioxidant system of the gut. Taking into account low carnitine content in grains and poultry and pig diet formulations with limited amounts of animal proteins, carnitine requirement and possible inadequacy in commercial poultry and pig nutrition should receive more attention. Furthermore, protective roles of carnitine in stress conditions of commercial poultry and pig production, including its immunomodulating properties, are of great importance. Therefore, a development of carnitine-containing antioxidant compositions supplying via drinking water seems to be an important way forward in decreasing the detrimental consequence of various stresses in poultry and pig production.

연령이 홀스타인 육우송아지 등심 및 우둔의 카르니틴, 유리아미노산 및 핵산 관련 물질 함량에 미치는 영향

This study was conducted to investigate the effect of age on the contents of carnitine, free amino acid, and nucleotide-related compound in Holstein calf meat. Twenty calves were allocated into four age groups (3, 6, 9, or 12 mon of age; n=5/group), and ribeye (M. longissimus dorsi) and top round (M. semimembranosus) were excised from left side of each carcass on day 1 post-mortem. Carnitine contents for ribeye and top round were 0.79～1.16 and 0.65～1.26 mg/100 g, respectively, and those showed a tendency to be the highest in 3 mon group. The contents of majority of free amino acids were the highest (p<0.05) in ribeye and top round from 12 mon group. The contents of adenosine monophosphate, inosine monophosphate, and inosine were the highest (p<0.05) in ribeye and top round from 12 mon group, but hypoxanthine content was the lowest (p<0.05) in those from 12 mon group. These findings suggest that age decreases the carnitine content but increases free amino acid and good taste-related nucleotides contents in Holstein calf meat.

Carnitine deficiency: Risk factors and incidence in children with epilepsy.

Carnitine deficiency is relatively common in epilepsy; risk factors reportedly include combination antiepileptic drug (AED) therapy with valproic acid (VPA), young age, intellectual disability, diet and enteral or parenteral feeding. Few studies have examined the correlation between each risk factor and carnitine deficiency in children with epilepsy. We examined the influence of these risk factors on carnitine deficiency, and identified a formula to estimate plasma free carnitine concentration in children with epilepsy. Sixty-five children with epilepsy and 26 age-matched controls were enrolled. Plasma carnitine concentrations were measured using an enzyme cycling assay, and correlations were sought with patients' other clinical characteristics. Carnitine deficiency was found in approximately 17% of patients with epilepsy and was significantly associated with carnitine-free enteral formula only by tube feeding, number of AEDs taken (independent of VPA use), body weight (BW), body height and Gross Motor Function Classification System (GMFCS) score. Stepwise multiple linear regression analysis indicated that carnitine concentration (in μmol/L) could be accurately estimated from a formula that does not require blood testing: 42.44+0.14×(BW in kg)-18.16×(feeding)-3.19×(number of AEDs), where feeding was allocated a score of 1 for carnitine-free enteral formula only by tube feeding and 0 for taking food orally (R(2)=0.504, P<0.001). Carnitine-free enteral formula only by tube feeding, multiple AED treatment and low BW are risk factors for carnitine deficiency in children with epilepsy. l-carnitine should be administered to children at risk of deficiency to avoid complications. Treatment decisions can be informed using an estimation formula that does not require blood tests.

Related factor of serum carnitine deficiency and influence of its deficiency on the length of hospital stay in critical ill patients

To investigate the related factors of serum carnitine deficiency in critical ill patients, and the influence of its deficiency on the length of hospital stay. A prospective study was conducted. Critical ill patients with acute physiology and chronic health evaluation II (APACHEII) score>12 admitted to Department of Critical Care Medicine of the First Affiliated Hospital of Sun Yat-sen University from March 2013 to September 2013 were enrolled. Serum carnitine concentration and indexes of organ function were determined, and the tolerance of enteral nutrition within 5 days, the length of hospital stay, the length of intensive care unit (ICU) stay, and the hospital mortality were recorded. The relationship between serum carnitine and indexes mentioned above was analyzed. Thirty critically ill patients were enrolled. Serum carnitine concentration was very low in all critically ill patients, i.e. (8.92 ± 5.05) μmol/L (normal reference value at 43.5 μmol/L) at hospital admission. Serum carnitine concentration in patients with APACHEII score>23 (7 cases) was significantly lower than that in those with APACHEII score 12-23 (23 cases, μmol/L: 5.33 ± 1.72 vs. 10.02 ± 5.24, t=2.300, P=0.001). Serum carnitine concentration in patients with serum total bilirubin(TBil)>19 μmol/L (9 cases) was significantly lower than that in those with TBil≤19 μmol/L (21 cases, μmol/L: 5.54 ± 2.70 vs. 9.84 ± 5.08, t=2.750, P=0.014). Serum carnitine concentration was negatively correlated with the APACHEII score and the TBil (r=-0.387, P=0.035; r=-0.346, P=0.048). During the 5-day observation period, enteral feeding amount [(5 134 ± 1 173) mL] was positively correlated with serum carnitine concentration(r=0.430, P=0.022). In 30 critical patients, the incidence of abdominal distension was 40.0% (12/30), and the serum carnitine concentration of patients with abdominal distension was lower compared with that of patients without abdominal distension (μmol/L: 7.83 ± 4.98 vs. 9.12 ± 5.35, t=0.707, P=0.383). The incidence of diarrhea was 26.7% (8/30), and the serum carnitine concentration of diarrhea patients was lower compared with that of patients without diarrhea (μmol/L: 8.27 ± 5.78 vs. 9.73 ± 4.78, t=0.607, P=0.576). The mean length of hospital stay was (34.72 ± 16.66) days. The serum carnitine concentrations in patients with hospital stay ≥ 45 days (8 cases) were lower compared with those in those <45 days (22 cases, μmol/L: 5.71 ± 3.23 vs. 9.95 ± 5.26, t=1.627, P=0.020). No correlation was found between serum carnitine concentrations and the hospital stay (r=-0.165, P=0.385). The length of ICU stay was (18.60 ± 10.72) days. Serum carnitine concentration in patients with the length of ICU stay>7 days (27 cases) was slightly lower than that in those with the length of ICU stay ≤ 7 days (3 cases, μmol/L: 8.44 ± 5.00 vs. 13.24 ± 3.65, t=1.610, P=0.119). No correlation was found between serum carnitine concentrations and the length of ICU stay (r=-0.019, P= 0.293). In-hospital mortality was 26.67% (8/30). No significant difference in serum carnitine concentrations was found between the death group and the survival group (μmol/L: 12.24 ± 6.52 vs. 7.72 ± 3.91, t=-1.846, P=0.098). No correlation was found between serum carnitine concentrations and in-hospital mortality (r=0.340, P=0.066). Carnitine deficiency is significant in critically ill patients, and it is correlated with disease severity and serum TBil. The total amount of lenteral feeding was lower, and hospital stay was prolonged in critically ill patients with low serum carnitine level.

Comparison of the amounts of endogenous bioactive compounds in raw and cooked meats from commercial broilers and indigenous chickens

A study was conducted to compare carnosine, anserine, betaine and carnitine contents of breast and leg (combined thigh and drumstick) meat from Korean native chickens (KNCs) and commercial broilers (CBs) at their market ages (100 and 32d, respectively) and to determine the changes in these compounds during moist heat cooking. In general, KNCs showed significantly higher histidyl dipeptide and carnitine contents and a lower betaine content than CBs (p<0.05). Significantly higher histidyl dipeptide contents were observed in breast meat, while leg meat had more betaine and carnitine contents (p<0.05). Significant decreases in the content of all compounds analysed in this study occurred during cooking (p<0.05). Meat from KNCs is a good source of carnosine, anserine, and carnitine compared to that from CBs, which has a higher content of betaine. In addition, the contents of these endogenous compounds are significantly affected by the meat portion and the cooking process (p<0.05).

Biomarkers of inflammation, metabolism, and oxidative stress in blood, liver, and milk reveal a better immunometabolic status in peripartal cows supplemented with Smartamine M or MetaSmart

The peripartal dairy cow experiences a state of reduced liver function coupled with increased inflammation and oxidative stress. This study evaluated the effect of supplementing basal diets with rumen-protected Met in the form of MetaSmart (MS) or Smartamine M (SM) (both from Adisseo Inc., Antony, France) during the peripartal period on blood and hepatic biomarkers of liver function, inflammation, and oxidative stress. Thirty-seven multiparous Holstein cows were fed the same basal diet from −50 to −21 d relative to expected calving [1.24Mcal/kg of dry matter (DM); no Met supplementation]. From −21 d to calving, the cows received diets (1.54Mcal/kg of DM) with no added Met (control, CON; n=13), CON plus MS (n=11), or CON plus SM (n=13). From calving through 30 d in milk (DIM), the cows received the same postpartal diet (1.75Mcal/kg of DM; CON), or CON plus MS or CON plus SM. Liver and blood samples were harvested at various time points from −21 to 21 d relative to calving. Preplanned contrasts of CON versus SM + MS during prepartum (−21 and −10 d before calving) and postpartum (7, 14, and 21 d after calving) responses were evaluated. Cows fed MS or SM compared with CON had lower overall concentrations of plasma ceruloplasmin and serum amyloid A (SAA). Compared with CON, Met-supplemented cows had greater overall plasma oxygen radical absorbance capacity. Liver concentrations of glutathione and carnitine also were greater overall with Met supplementation. Milk choline and liver phosphatidylcholine were lower overall in cows fed Met compared with controls. Liver tissue choline concentrations did not differ. Data indicate that supplemental Met enhanced de novo glutathione and carnitine synthesis in liver and, thus, increased antioxidant and β-oxidation capacity. The greater decrease of IL-6 after calving coupled with lower ceruloplasmin and SAA in Met-supplemented cows indicated a reduction in proinflammatory signaling within liver. The lower hepatic phosphatidylcholine in Met-supplemented cows might have been associated with greater assembly or export of very low density lipoproteins. Overall, biomarker analyses in blood and tissue indicate that the beneficial effect of feeding SM and MS on postpartal cow performance is due in part to a better immunometabolic status.

Differential effects of oral and intravenous l-carnitine on serum lipids: is the microbiota the answer?

l-carnitine (free carnitine) transports cytosolic long-chain fatty acids as acylcarnitines across the inner mitochondrial membrane for β-oxidation and subsequent ATP production in the mitochondria. The endogenous carnitine pool comprises free l-carnitine as well as short-, medium- and long-chain fatty acid esters (acyl-carnitines) and depends on absorption of l-carnitine from dietary sources, endogenous biosynthesis and renal tubular reabsorption from glomerular filtrate [1]. More than 99% of the carnitine pool is located outside of plasma. Carrier-mediated transport ensures high tissue-to-plasma concentration ratios in tissues that depend critically on fatty acid oxidation, such as heart and muscle. Myocytes have one of the highest intracellular carnitine concentrations in the body, and red meat is a rich source of dietary carnitine. Absorption of orally administered l-carnitine is very variable and ranges from 5 to 18% for pharmacological doses of up to 75% for dietary l-carnitine. The low bioavailability depends both on transport kinetics and on l-carnitine metabolism by intestinal bacteria [1, 2]. The renal clearance of l-carnitine (1–3 mL/min) is much lower than the glomerular filtration rate because of extensive (98–99%) tubular reabsorption. The lack of reabsorption during the haemodialysis procedure results in large losses of l-carnitine in dialysate. The existence of a threshold concentration for tubular reabsorption results in much higher renal clearances after intravenous administration of high doses [3].

Effect of Sex on Flavor-related and Functional Compounds in Freeze-dried Broth Made from Korean Native Chicken

Studies on the flavour characteristics of meat-based broth, quantification of flavour-related and functional compounds, and factors affecting the availability of such compounds are minimal. The present study was designed to determine the effects of sex on flavor-related and functional compounds in freeze-dried broth (FDB) made from Korean native chickens (KNC). Male and female KNC from a commercial strain (WoorimatdagTM) were reared under similar commercial conditions. FDB was separately prepared using male and female birds aged 100 d (six birds of each sex) and analyzed for nucleotide, free amino acid, betaine, carnitine, carnosine, anserine, and creatine contents, and fatty acid composition. The levels of betaine, carnitine and creatine in FDB were not significantly different between the two sexes (p>0.05) in KNC. Carnosine and anserine were not detected in FDB samples. However, FDB from female chickens had significantly higher inosine-5-monophosphate and arachidonic acid contents than did FDB from male chickens. FDB prepared with male KNC contained higher levels of inosine, linoleic acid, glycine, alanine, lysine, and serine (p<0.05). However, glutamic acid, oleic acid, and DHA were present in comparable amounts (p>0.05) in FDB made from male and female KNC. Our findings suggest that the sex of KNC has significant effect on the contents of flavor-related compounds, but not functional compounds.

Distribution, molecular structure and functional analysis of carnitine transporter (SLC22A5) in canine lens epithelial cells

AbstractPurpose While carnitine has been reported to have an anti‐oxidative role on the ocular surface, there has been no report on the existence of a carnitine transporter (SLC22A5) in the lens. Therefore, we investigated the carnitine transport activity of canine lens epithelial cells (LEC) and determined the molecular structure of canine SLC22A5.Methods The primary lens epithelial cells of dog were transfected with the expression plasmid DNA of large T antigen from replication origin‐defective simian virus 40 (SV40), then cloned using glass a cylinder. The transport activities of carnitine in lens epithelial cells were measured. The cDNA sequences of SLC22A5 were also determined.Results The carnitine transport activity was 7.16 + 0.48 pmol/mg protein/30 min. Butyrobetaine, the analogue of carnitine, reduced 30% of the activity at 50 microM. A coding sequence of canine carnitine transporter was 1694 bp long and was predicted to encode 557 amino acid polypeptides. The deduced amino acid sequence of canine carnitine transporter showed &gt; 80% similarity to that of mouse and human. Western blot analysis detected the band at 60 kDa in the membrane of lens epithelial cells.Conclusion Lens epithelial cells possess SLC22A5. The high content of carnitine in the lens is possibly transported from aqueous humor by SLC22A5.

Pharmacological doses of niacin stimulate the expression of genes involved in carnitine uptake and biosynthesis and improve the carnitine status of obese Zucker rats.

BackgroundActivation of peroxisome proliferator-activated receptor (PPAR)α and PPARδ causes an elevation of tissue carnitine concentrations through induction of genes involved in carnitine uptake [novel organic cation transporter 2, (OCTN2)], and carnitine biosynthesis [γ-butyrobetaine dioxygenase (BBD), 4-N-trimethyl-aminobutyraldehyde dehydrogenase (TMABA-DH)]. Recent studies showed that administration of the plasma lipid-lowering drug niacin causes activation of PPARα and/or PPARδ in tissues of obese Zucker rats, which have a compromised carnitine status and an impaired fatty acid oxidation capacity. Thus, we hypothesized that niacin administration to obese Zucker rats is also able to improve the diminished carnitine status of obese Zucker rats through PPAR-mediated stimulation of genes involved in carnitine uptake and biosynthesis.MethodsTo test this hypothesis, we used plasma, muscle and liver samples from a recent experiment with obese Zucker rats, which were fed either a niacin-adequate diet (30 mg niacin/kg diet) or a diet with a pharmacological niacin dose (780 mg niacin/kg diet), and determined concentrations of carnitine in tissues and mRNA and protein levels of genes critical for carnitine homeostasis (OCTN2, BBD, TMABA-DH). Statistical data analysis of all data was done by one-way ANOVA, and Fisher’s multiple range test.ResultsRats of the obese niacin group had higher concentrations of total carnitine in plasma, skeletal muscle and liver, higher mRNA and protein levels of OCTN2, BBD, and TMABA-DH in the liver and higher mRNA and protein levels of OCTN2 in skeletal muscle than those of the obese control group (P < 0.05), whereas rats of the obese control group had lower concentrations of total carnitine in plasma and skeletal muscle than lean rats (P < 0.05).ConclusionThe results show for the first time that niacin administration stimulates the expression of genes involved in carnitine uptake and biosynthesis and improves the diminished carnitine status of obese Zucker rats. We assume that the induction of genes involved in carnitine uptake and biosynthesis by niacin administration is mediated by PPAR-activation.

Changes in endogenous bioactive compounds of Korean native chicken meat at different ages and during cooking

This study aimed to examine the effect of bird age on the contents of endogenous bioactive compounds, including carnosine, anserine, creatine, betaine, and carnitine, in meat from a certified meat-type commercial Korean native chicken strain (KNC; Woorimatdag). Additionally, the effects of the meat type (breast or leg meat) and the state of the meat (raw or cooked) were examined. Cocks of KNC were raised under similar standard commercial conditions at a commercial chicken farm. At various ages (10, 11, 12, 13, and 14 wk), breast and leg meats from a total of 10 birds from each age group were obtained. Raw and cooked meat samples were then prepared separately and analyzed for bioactive compounds. The age of the KNC had a significant effect only on the betaine content. The breast meat of KNC had higher amounts of carnosine and anserine but had lower amounts of betaine and carnitine than the leg meat (P < 0.05). The KNC meat lost significant amounts of all bioactive compounds during cooking (P < 0.05). Leg meat had high retention percentages of carnosine and anserine after cooking, whereas breast meat showed almost complete retention of betaine and carnitine. The results of this study provide useful and rare information regarding the presence, amounts, and determinants of endogenous bioactive compounds in KNC meat, which can be useful for selection and breeding programs, and also for popularizing indigenous chicken meat.

Dietary L-carnitine supplementation increases lipid deposition in the liver and muscle of yellow catfish (Pelteobagrus fulvidraco) through changes in lipid metabolism.

Carnitine has been reported to improve growth performance and reduce body lipid content in fish. Thus, we hypothesised that carnitine supplementation can improve growth performance and reduce lipid content in the liver and muscle of yellow catfish (Pelteobagrus fulvidraco), a commonly cultured freshwater fish in inland China, and tested this hypothesis in the present study. Diets containing l-carnitine at three different concentrations of 47 mg/kg (control, without extra carnitine addition), 331 mg/kg (low carnitine) and 3495 mg/kg (high carnitine) diet were fed to yellow catfish for 8 weeks. The low-carnitine diet significantly improved weight gain (WG) and reduced the feed conversion ratio (FCR). In contrast, the high-carnitine diet did not affect WG and FCR. Compared with the control diet, the low-carnitine and high-carnitine diets increased lipid and carnitine contents in the liver and muscle. The increased lipid content in the liver could be attributed to the up-regulation of the mRNA levels of SREBP, PPARγ, fatty acid synthase (FAS) and ACCa and the increased activities of lipogenic enzymes (such as FAS, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and malic enzyme) and to the down-regulation of the mRNA levels of the lipolytic gene CPT1A. The increased lipid content in muscle could be attributed to the down-regulation of the mRNA levels of the lipolytic genes CPT1A and ATGL and the increased activity of lipoprotein lipase. In conclusion, in contrast to our hypothesis, dietary carnitine supplementation increased body lipid content in yellow catfish.

Trimethylamine generation in patients receiving hemodialysis treated with l-carnitine.

Hepatic biotransformation of gut microbiota-derived trimethylamine (TMA) to trimethylamine N-oxide (TMAO) may enhance cardiovascular risk [1, 2]. The source of TMA is fish-derived TMAO [3], meat-derived betaine/choline/phosphatidylcholine [1, 2], and the medicine l-carnitine [4]. There is no clear information on the metabolic fate of TMA/TMAO in patients receiving hemodialysis and treated with l-carnitine orally and intravenously. We report data showing that plasma TMA/TMAO concentrations in hemodialysis patients may be in the same range as those of healthy subjects consuming a typical diet in Japan. Fourteen subjects, randomly selected from a cohort of 18 male and 6 female Japanese patients (47–89 years) with diabetes mellitus or chronic glomerulonephritis who had undergone hemodialysis for several years, were divided into five untreated controls, five treated with 1000 mg of l-carnitine (l-Cartin injection, Otsuka, Tokyo, Japan) intravenously on 3 days (Days 1, 3 and 5) over 1 week, and four treated with 300 mg of oral l-carnitine (l-Cartin tablets, Otsuka) three times per day for 7 days. Ten healthy volunteers (22–59 years) were also enrolled. This study was approved by the ethics committees of Minami Ikebukuro Clinic and Showa Pharmaceutical University. Total carnitine and TMA/TMAO concentrations were determined by Kainos laboratories (Tokyo, Japan) and by gas chromatography [3]. Carnitine concentrations for 2–8 weeks after treatment with l-carnitine were significantly higher than those in the untreated group (Figure 1). Plasma TMA concentrations after oral treatment with l-carnitine were higher than those of the untreated group. TMAO concentrations did not increase significantly after treatments and were in the range of daily interindividual variations. In separate observations in 22 of the 24-patient cohort, pre-dialysis plasma concentrations of carnitine (33 ± 4 µM, mean ± SD), TMA (34 ± 20 µM) and TMAO (189 ± 94 µM) were decreased by hemodialysis (12 ± 8, 25 ± 8 and 140 ± 77 µM, respectively). These concentration ranges were comparable with TMA (26 ± 17 µM) and TMAO (197 ± 100 µM) in healthy volunteers (n = 10). The present plasma levels of TMA and/or TMAO in Japanese patients were one or two orders of magnitude higher than the reported concentrations in Caucasians [1, 2], but were consistent with a review of patients undergoing hemodialysis [4]. Fig. 1. Plasma concentrations of total l-carnitine (A), TMA (B) and TMAO (C) in untreated patients (circles) and in patients treated with l-carnitine intravenously (triangles) and orally (squares). The three bars are averages of the three groups (n = 4 or 5). ... Some TMA formation in a Japanese cohort treated with l-carnitine orally was confirmed, but the levels of TMA/TMAO both pre-/post-dialysis in patients not receiving l-carnitine were in the same ranges as those of the control subjects.

Human serum acylcarnitine profiles in different glucose tolerance states

AimsTo understand the relationship between serum acylcarnitine profiles and glucose tolerance status. MethodsWe analyzed 61 subjects who were divided into three groups based on their glucose tolerance status: normal glucose tolerance (NGT; n=20,M/F=9/11, mean age 48 years), pre-diabetes (Pre-DM; n=20,M/F=11/9, mean age 51 years), or newly diagnosed type 2 diabetes mellitus (T2DM; n=21,M/F=8/13, mean age 49 years). Fasting serum free carnitine and acylcarnitine concentrations were determined using isotope dilution electrospray ionization mass spectrometry coupled with high performance liquid chromatography. ResultsIn comparison with NGT subjects, Pre-DM and type 2 diabetes subjects showed serum metabonomic changes highlighted by dysregulation of mitochondrial fatty acid combustion. Of the long-chain carnitine esters, significantly higher palmitoylcarnitine (C16), 3-OH-hexadecanoylcarnitine (C16-OH), carnitine C20, carnitine C22, and carnitine C24 concentrations (all P<0.05) were noted in the newly diagnosed type 2 diabetes group, and even the pre-diabetes group. ConclusionsThis research provides further evidence of alterations in serum acylcarnitine profiles being associated with worse glucoseintolerance. The findings may suggest different degrees of involvement of dysregulated mitochondrial function and incomplete long-chain fatty acid oxidation pathways in the natural course of type 2 diabetes.