Muscle Carnitine Research Articles

A moderate excess of dietary lysine lowers plasma and tissue carnitine concentrations in pigs

This study was performed to investigate whether dietary lysine concentration influences the carnitine status of pigs. Therefore, an experiment with twenty young pigs with an average body weight of 21 kg was performed which were fed either a control diet (9.7 g lysine/kg) or a diet with a moderate excess of lysine (16.8 g lysine/kg). Concentrations of all the other amino acids did not differ between the diets. Pigs fed the high-lysine diet had lower concentrations of free and total carnitine in plasma, liver, kidney and skeletal muscle than control pigs (P<0.05). Pigs fed the high-lysine diet moreover had an increased concentration of trimethyllysine (TML), a reduced mRNA abundance of TML dioxygenase and reduced concentrations of gamma-butyrobetaine (BB) in muscle, indicating that the conversion of TML into BB in muscle was impaired. Concentrations of BB, the metabolic precursor of carnitine, in plasma, liver and kidney were also reduced in pigs fed the high-lysine diet while the activity of BB dioxygenase in kidney was not different and that in liver was even increased compared to control pigs (P<0.05). In conclusion, this study shows that a moderate dietary excess of lysine lowers plasma and tissue carnitine concentrations in pigs. Reduced concentrations of BB in liver and kidney suggest that the depressed carnitine status was likely caused by a decreased rate of carnitine synthesis due to a diminished availability of carnitine precursor, probably mainly as a result of an impaired BB formation in muscle.

Combined effects of hypoxia and endurance training on lipid metabolism in rat skeletal muscle

To determine whether endurance training can counterbalance the negative effects of hypoxia on mitochondrial phosphorylation and expression of the long chain mitochondrial fatty acid transporter muscle carnitine palmitoyl transferase 1 (mCPT-1). Male Wistar rats were exposed either to hypobaric hypoxia (at a simulated altitude of approximately 4000 m, PIO(2) approximately 90 mmHg) or to normoxia (sea level) for 5 weeks. In each environment, rats were randomly assigned to two groups. The trained group went through a 5-week endurance training programme. The control group remained sedentary for the same time period. Muscle fatty acid oxidation capacity was evaluated after the 5-week period on isolated mitochondria prepared from quadriceps muscles with the use of palmitoylcarnitine or pamitoylCoA + carnitine. Chronic hypoxia decreased basal (V(0), -31% with pamitoylCoA + carnitine and -21% with palmitoylcarnitine, P < 0.05) and maximal (V(max), -31% with pamitoylCoA + carnitine, P < 0.05) respiration rates, hydroxyacylCoA dehydrogenase activity (-48%, P < 0.05), mCPT-1 activity index (-34%, P < 0.05) and mCPT-1 protein content (-34%, P < 0.05). Five weeks of endurance training in hypoxia brought V(0), mCPT-1 activity index and mCPT-1 protein content values back to sedentary normoxic levels. Moreover, in the group trained in hypoxia, V(max) reached a higher level than in the group that maintained a sedentary lifestyle in normoxia (24.2 nmol O(2). min(-1) . mg(-1) for hypoxic training vs. 19.9 nmol O(2) . min(-1) . mg(-1) for normoxic sedentarity, P < 0.05). Endurance training can attenuate chronic hypoxia-induced impairments in mitochondrial fatty acid oxidation. This training effect seems mostly mediated by mCPT-1 activity rather than by mCPT-1 content.

Sex steroid hormones affect carnitine concentrations of blood and organs in rats

Males and females exhibit different rates of central obesity, cardiovascular disease and diabetes. Furthermore, altered concentrations of sex steroid hormones can lead to altered rates of these diseases in the afflicted populations, suggesting these hormones can affect metabolism and, in the long term, have clinical repercussions. Carnitine, an amino acid derivative involved in fat oxidation, was used to examine differences in metabolism between the sexes based on changes in the hormonal milieu. Rats (178 males and 176 females) were administered one of the following treatments: estradiol injection, testosterone injection, castration, and hypophysectomy. Total carnitine was measured in plasma, liver, heart, muscle, and epididymis. In both sexes, estradiol appears to increase liver carnitine while decreasing plasma, muscle and heart carnitine; testosterone, on the other hand, increases plasma, muscle and heart carnitine. In males, estradiol decreases and testosterone increases epididymis carnitine. Hypophysectomy decreased carnitine in all compartments for males and all compartments except for heart and muscle in females. This study demonstrates that estradiol, testosterone and the pituitary gland greatly influence carnitine concentrations of the body and are key to the observed sex differences in carnitine.

Carnitine compartmentalization in surgery patients

Carnitine, an amino acid derivative, is involved in the transport of fatty acids into the mitochondrial matrix for βoxidation. Plasma carnitine is often used as a clinical indicator of the carnitine status throughout the body, but the carnitine concentration in organs and the relationship of carnitine compartments within the body are usually not known. We measured plasma carnitine collected before (PC) and during anesthesia (Surg‐PC), red blood cell carnitine collected before (RC) and during anesthesia (Surg‐RC), muscle carnitine (MuC) collected during general anesthesia, and in approximately half of the patients liver carnitine (LC) collected during general anesthesia. Total carnitine values of the various compartments are shown in the table below.Surg‐PC was lower than PC (p&lt;.05), but RC and Surg‐RC did not differ. Correlations of MuC or LC with any of the blood carnitine parameters indicated that less than 15 percent of the tissue carnitine concentration could be predicted by the blood carnitine parameters. Neither plasma carnitine nor red blood cell carnitine appears to be a strong predictor of carnitine status in tissue compartments.

Bitter melon extracts suppressed differentiation and triglyceride content of 3T3‐L1 adipocytes

Bitter melon (BM; Momordica charantia) supplementation slows weight gain and tissue fat accumulation in fat diet‐induced obese rat. Liver and muscle carnitine palmitoyl transferase‐I expression was enhanced in BM rats, suggesting increased lipid oxidation. This study was designed to determine if extracts from BM juice can suppress triglyceride (TG) content in the 3T3‐L1 cell line. 3T3‐L1 pre‐adipocytes were induced to differentiate in the presence or absence of an ethanol‐water extract of BM juice. The latter was obtained by stepwise gradient elution of an organic extract of BM juice. Two fractions (eluted by 10% &amp; 30% ethanol respectively and then freeze‐dried; F2 at 350μg/mL &amp; F3 at 50μg/mL) were found to reduce TG content on day 10 (p&lt;0.01, F3) &amp; day 12 (p&lt;0.01, both); and GPDH activity on day 10 &amp; 12 (p&lt;0.01, both) of a 12‐day study. Two‐way ANOVA indicated reduced mRNA expression of fatty acid synthase (p&lt;0.001), acetyl CoA carboxylase 1 (p&lt;0.01) and Glut‐4 (p&lt;0.01) in BM‐treated adipocytes. With F3, these effects primarily occurred between days 8–10. Downregulation of PPARγ (p&lt;0.001) and SREBP‐1c (p&lt;0.001) mRNA expression was observed in F3‐treated cells on day 12. The data suggest that bioactive ingredient(s) in BM may suppress TG synthesis in 3T3‐L1 cells through suppressing the expression of certain lipogenic genes and transcription factors. (Supported by the Faculty Development Fund, HKU)

Effect of Glycine Propionyl-L-Carnitine on Aerobic and Anaerobic Exercise Performance

The purpose of this study was to evaluate the effect of glycine propionyl-L-carnitine (GPLC) supplementation and endurance training for 8 wk on aerobic- and anaerobic-exercise performance in healthy men and women (age 18-44 yr). Participants were randomly assigned to 1 of 3 groups: placebo (n=9), 1 g/d GPLC (n=11), or 3 g/d GPLC (n=12), in a double-blind fashion. Muscle carnitine (vastus lateralis), VO(2peak), exercise time to fatigue, anaerobic threshold, anaerobic power, and total work were measured at baseline and after an 8-wk aerobic-training program. There were no statistical differences (p> .05) between or within the 3 groups for any performance-related variable or muscle carnitine concentrations after 8 wk of supplementation and training. These results suggest that up to 3 g/d GPLC for 8 wk in conjunction with aerobic-exercise training is ineffective for increasing muscle carnitine content and has no significant effects on aerobic- or anaerobic-exercise performance.

Legal pre-event nutritional supplements to assist energy metabolism

Physical training and proper nutrition are paramount for success in sport. A key tissue is skeletal muscle, as the metabolic pathways that produce energy or ATP allow the muscles to complete the many activities critical to success in sport. The energy-producing pathways must rapidly respond to the need for ATP during sport and produce energy at a faster rate or for a longer duration through training and proper nutrition which should translate into improved performance in sport activities. There is also continual interest in the possibility that nutritional supplements could further improve muscle metabolism and the provision of energy during sport. Most legal sports supplements do not improve performance following oral ingestion. However, three legal supplements that have received significant attention over the years include creatine, carnitine and sodium bicarbonate. The ingestion of large amounts of creatine for 4-6 days increases skeletal muscle creatine and phosphocreatine contents. The majority of the experimental evidence suggests that creatine supplementation can improve short-term exercise performance, especially in sports that require repeated short-term sprints. It may also augment the accretion of skeletal muscle when taken in combination with a resistance-exercise training programme. Supplementary carnitine has been touted to increase the uptake and oxidation of fat in the mitochondria. However, muscle carnitine levels are not augmented following oral carnitine supplementation and the majority of well-controlled studies have reported no effect of carnitine on enhancing fat oxidation, Vo(2max) or prolonged endurance exercise performance. The ingestion of sodium bicarbonate before intense exercise decreases the blood [H+] to potentially assist the efflux of H+ from the muscle and temper the metabolic acidosis associated with intense exercise. Many studies have reported performance increases in laboratory-based cycling tests and simulated running races in the field following sodium bicarbonate ingestion where the need for ATP from substrate phosphorylation is high. However, other studies have reported no benefit and the incidence of negative side effects is high.

Clofibrate treatment up-regulates novel organic cation transporter (OCTN)-2 in tissues of pigs as a model of non-proliferating species

Recent studies have shown that treatment of rodents with agonists of peroxisome proliferator-activated receptor (PPAR)-α causes an up-regulation of novel organic cation transporter (OCTN)-2, a carnitine transporter, and increases carnitine concentration in the liver. This study was performed to investigate whether such effects occur also in pigs which like humans have a lower expression of PPARα and are less responsive to treatment with PPARα agonists than rodents. An experiment with 18 pigs was performed which were fed a control diet or the same diet supplemented with 5 g clofibrate/kg for 28 days. Pigs treated with clofibrate had higher relative mRNA concentrations of OCTN2 in liver (3.1-fold), skeletal muscle (1.5-fold) and epithelial cells from small intestine (1.8-fold) than control pigs ( P < 0.05). Pigs treated with clofibrate had also higher concentrations of free and total carnitine in the liver and a higher concentration of free carnitine in skeletal muscle than control pigs ( P < 0.05). Concentrations of γ-butyrobetaine, the precursor of endogenous formation of carnitine, in liver, muscle and plasma did not differ between both groups; the activity of γ-butyrobetaine dioxygenase, the rate limiting enzyme of carnitine synthesis, in the liver was lower in pigs treated with clofibrate than in control pigs ( P < 0.05). This study shows for the first time that treatment with a PPARα agonist causes an up-regulation of OCTN2 in liver, muscle and enterocytes from small intestine of pigs. This in turn increases carnitine concentrations in liver and muscle probably by enhancing carnitine uptake into cells.

Cardiac PPARα Protein Expression is Constant as Alternate Nuclear Receptors and PGC‐1 Coordinately Increase During the Postnatal Metabolic Transition

Gene expression data obtained in mouse heart indicate that increased expression for the nuclear receptor, peroxisomal proliferator activated receptor (PPAR), prompts the postnatal transition from predominantly carbohydrate to fatty acid oxidation preference. However, no phenotypic or proteomic data are available to confirm downstream signaling and metabolic transition in mice. We studied the hypothesis that shifts in nuclear receptor expression trigger the newborn metabolic switch in a newborn sheep. This species is well characterized with regards to developmental changes in substrate oxidative metabolism. Heart tissues from fetal (130 days gestation), newborn 24 hours, and 30-day old lambs were evaluated for protein expression from multiple enzymes controlling oxidative metabolism as well as principal nuclear receptors and coactivators. Although muscle and liver type carnitine palmitoyl transferases I showed no significant changes to correspond to the metabolic transition, hexokinase II protein content showed a profound transient drop, and pyruvate dehydrogenase kinase steadily increased. PPAR showed no increases preceding or during the transition, while peroxisomal proliferator activated receptor gamma coactivator-1 (PGC-1) increased approximately 20-fold transiently in newborn heart in conjunction with significant increases in thyroid hormone receptor 1 and retinoid-activated receptor . These data challenge the paradigm that increases in PPAR prompt the postnatal metabolic switch, and suggest that other nuclear receptors play a major role. As thyroid hormone (TH) modulates PGC-1 expression in sheep during development, these data further suggest that well-characterized perinatal TH surge in sheep contributes to this metabolic switch.

Dietary oxidised fat up regulates the expression of organic cation transporters in liver and small intestine and alters carnitine concentrations in liver, muscle and plasma of rats

It has been shown that treatment of rats with clofibrate, a synthetic agonist of PPARalpha, increases mRNA concentration of organic cation transporters (OCTN)-1 and -2 and concentration of carnitine in the liver. Since oxidised fats have been demonstrated in rats to activate hepatic PPARalpha, we tested the hypothesis that they also up regulate OCTN. Eighteen rats were orally administered either sunflower-seed oil (control group) or an oxidised fat prepared by heating sunflower-seed oil, for 6 d. Rats administered the oxidised fat had higher mRNA concentrations of typical PPARalpha target genes such as acyl-CoA oxidase, cytochrome P450 4A1 and carnitine palmitoyltransferases-1A and -2 in liver and small intestine than control rats (P < 0.05). Furthermore, rats treated with oxidised fat had higher hepatic mRNA concentrations of OCTN1 (1.5-fold) and OCTN2 (3.1-fold), a higher carnitine concentration in the liver and lower carnitine concentrations in plasma, gastrocnemius and heart muscle than control rats (P < 0.05). Moreover, rats administered oxidised fat had a higher mRNA concentration of OCTN2 in small intestine (2.4-fold; P < 0.05) than control rats. In conclusion, the present study shows that an oxidised fat causes an up regulation of OCTN in the liver and small intestine. An increased hepatic carnitine concentration in rats treated with the oxidised fat is probably at least in part due to an increased uptake of carnitine into the liver which in turn leads to reduced plasma and muscle carnitine concentrations. The present study supports the hypothesis that nutrients acting as PPARalpha agonists influence whole-body carnitine homeostasis.

Hypoxia-inducible factor 1 mediates hypoxia-induced cardiomyocyte lipid accumulation by reducing the DNA binding activity of peroxisome proliferator-activated receptor α/retinoid X receptor

In response to cellular hypoxia, cardiomyocytes adapt to consume less oxygen by shifting ATP production from mitochondrial fatty acid β-oxidation to glycolysis. The transcriptional activation of glucose transporters and glycolytic enzymes by hypoxia is mediated by hypoxia-inducible factor 1 (HIF-1). In this study, we examined whether HIF-1 was involved in the suppression of mitochondrial fatty acid β-oxidation in hypoxic cardiomyocytes. We showed that either hypoxia or adenovirus-mediated expression of a constitutively stable hybrid form (HIF-1α/VP16) suppressed mitochondrial fatty acid metabolism, as indicated by an accumulation of intracellular neutral lipid. Both treatments also reduced the mRNA levels of muscle carnitine palmitoyltransferase I which catalyzes the rate-limiting step in the mitochondrial import of fatty acids for β-oxidation. Furthermore, adenovirus-mediated expression of HIF-1α/VP16 in cardiomyocytes under normoxic conditions also mimicked the reduction in the DNA binding activity of peroxisome proliferator-activated receptor α (PPARα)/retinoid X receptor (RXR), in the presence or absence of a PPARα ligand. These results suggest that HIF-1 may be involved in hypoxia-induced suppression of fatty acid metabolism in cardiomyocytes by reducing the DNA binding activity of PPARα/RXR.

A Conserved Role for Phosphatidylinositol 3-Kinase but Not Akt Signaling in Mitochondrial Adaptations that Accompany Physiological Cardiac Hypertrophy

Physiological cardiac hypertrophy is associated with mitochondrial adaptations that are characterized by activation of PGC-1alpha and increased fatty acid oxidative (FAO) capacity. It is widely accepted that phosphatidylinositol 3-kinase (PI3K) signaling to Akt1 is required for physiological cardiac growth. However, the signaling pathways that coordinate physiological hypertrophy and metabolic remodeling are incompletely understood. We show here that activation of PI3K is sufficient to increase myocardial FAO capacity and that inhibition of PI3K signaling prevents mitochondrial adaptations in response to physiological hypertrophic stimuli despite increased expression of PGC-1alpha. We also show that activation of the downstream kinase Akt is not required for the mitochondrial adaptations that are secondary to PI3K activation. Thus, in physiological cardiac growth, PI3K is an integrator of cellular growth and metabolic remodeling. Although PI3K signaling to Akt1 is required for cellular growth, Akt-independent pathways mediate the accompanying mitochondrial adaptations.

Hormonal and nutritional regulation of muscle carnitine palmitoyltransferase I gene expression in vivo

Transgenic mice carrying the human heart muscle carnitine palmitoyltransferase I (M-CPTI) gene fused to a CAT reporter gene were generated to study the regulation of M-CPTI gene expression. When the mice were fasted for 48 h, CAT activity and mRNA levels increased by more than 2-fold in heart and skeletal muscle, but not liver or kidney. In the diabetic transgenic mice, there was a 2- to 3-fold increase in CAT activity and CAT mRNA levels in heart and skeletal muscle which upon insulin administration reverted to that observed with the control insulin sufficient transgenic mice. Feeding a high fat diet increased CAT activity and mRNA levels by 2- to 4-fold in heart and skeletal muscle of the transgenic mice compared to the control transgenic mice on regular diet. Overall, the M-CPTI promoter was found to be necessary for the tissue-specific hormonal and dietary regulation of the gene expression.

Carnitine Content in Different Muscles of Patients Receiving Maintenance Hemodialysis

Chronic hemodialysis may lead to losses of carnitine from plasma and muscles. The aim of the present study was a comparison of carnitine contents in different human muscles (brachioradialis muscle and rectus muscle of abdomen) and evaluation of the correlation between plasma and tissue carnitine concentrations in patients receiving hemodialysis and healthy control patients. The studies were performed in two groups of patients receiving hemodialysis. The first group included 37 patients (18 male, 19 female) (muscle specimen was taken from the brachioradialis muscle). The second group included 28 patients (15 male, 13 female) (muscle specimen was taken from the rectus muscle of abdomen). The other two separate groups of patients without renal involvement served as the controls. Significantly lower free plasma and free muscle carnitine (FMC) contents were noticed in patients receiving hemodialysis in comparison with the controls. Significantly higher total muscle carnitine (TMC) and FMC concentrations in the brachioradialis muscle in comparison with the rectus muscle of abdomen were observed in both the hemodialysis and control groups. Negative correlations between TMC, FMC, and FMC/TMC ratio versus duration of hemodialysis were found. No correlations between muscle and serum carnitine levels were observed. Patients receiving hemodialysis are carnitine deficient. Tissue carnitine depletion is related to hemodialysis duration. Carnitine concentration in blood does not represent the whole carnitine stores in patients receiving hemodialysis. Brachioradialis muscle carnitine contents are significantly higher than those in the rectus muscle of abdomen.

Dietary l-Carnitine Affects Periparturient Nutrient Metabolism and Lactation in Multiparous Cows

The objectives of this study were to determine the effects of dietary l-carnitine supplementation on liver lipid accumulation, hepatic nutrient metabolism, and lactation in multiparous cows during the periparturient period. Cows were assigned to treatments at d −25 relative to expected calving date and remained on the experiment until 56 d in milk. Treatments were 4 amounts of supplemental dietary carnitine: control (0 g/d of l-carnitine; n = 14); low carnitine (LC, 6 g/d; n = 11); medium carnitine (MC, 50 g/d; n = 12); and high carnitine (HC, 100 g/d; n = 12). Carnitine was supplied by mixing a feed-grade carnitine supplement with 113.5g of ground corn and 113.5g of dried molasses, which was then fed twice daily as a topdress to achieve desired daily carnitine intakes. Carnitine supplementation began on d −14 relative to expected calving and continued until 21 d in milk. Liver and muscle carnitine concentrations were markedly increased by MC and HC treatments. Milk carnitine concentrations were elevated by all amounts of carnitine supplementation, but were greater for MC and HC than for LC during wk 2 of lactation. Dry matter intake and milk yield were decreased by the HC treatment. The MC and HC treatments increased milk fat concentration, although milk fat yield was unaffected. All carnitine treatments decreased liver total lipid and triacylglycerol accumulation on d 10 after calving. In addition, carnitine-supplemented cows had higher liver glycogen during early lactation. In general, carnitine supplementation increased in vitro palmitate β-oxidation by liver slices, with MC and HC treatments affecting in vitro palmitate metabolism more potently than did LC. In vitro conversion of Ala to glucose by liver slices was increased by carnitine supplementation independent of dose. The concentration of nonesterified fatty acids in serum was not affected by carnitine. As a result of greater hepatic fatty acid β-oxidation, plasma β-hydroxybutyric acid was higher for the MC and HC treatments. Serum insulin was greater for all carnitine treatments, although plasma glucose was unaffected. Plasma urea N was lower and plasma total protein was higher for the MC and HC treatments. By decreasing liver lipid accumulation and stimulating hepatic glucose output, carnitine supplementation might improve glucose status and diminish the risk of developing metabolic disorders during early lactation.

New insights concerning the role of carnitine in the regulation of fuel metabolism in skeletal muscle

In skeletal muscle, carnitine plays an essential role in the translocation of long-chain fatty-acids into the mitochondrial matrix for subsequent beta-oxidation, and in the regulation of the mitochondrial acetyl-CoA/CoASH ratio. Interest in these vital metabolic roles of carnitine in skeletal muscle appears to have waned over the past 25 years. However, recent research has shed new light on the importance of carnitine as a regulator of muscle fuel selection. It has been established that muscle free carnitine availability may be limiting to fat oxidation during high intensity submaximal exercise. Furthermore, increasing muscle total carnitine content in resting healthy humans (via insulin-mediated stimulation of muscle carnitine transport) reduces muscle glycolysis, increases glycogen storage and is accompanied by an apparent increase in fat oxidation. By increasing muscle pyruvate dehydrogenase complex (PDC) activity and acetylcarnitine content at rest, it has also been established that PDC flux and acetyl group availability limits aerobic ATP re-synthesis at the onset of exercise (the acetyl group deficit). Thus, carnitine plays a vital role in the regulation of muscle fuel metabolism. The demonstration that its availability can be readily manipulated in humans, and impacts on physiological function, will result in renewed business and scientific interest in this compound.

Effect of l-Carnitine Infusion and Feed Restriction on Carnitine Status in Lactating Holstein Cows

Previously we determined that abomasal infusion of l-carnitine increased in vitro hepatic fatty acid oxidation, decreased liver lipid accumulation, and supported higher fat-corrected milk yield in feed-restricted lactating cows. The objectives of this study were to examine the effects of supplemental l-carni-tine and amount of feed intake on free carnitine and carnitine ester concentrations in liver, muscle, milk, and plasma of lactating dairy cows. Eight lactating Holstein cows (132±36 d in milk) were used in a replicated 4×4 Latin square design with 14-d periods to test factorial combinations of water or l-carnitine infusion (20g/d; d 5 to 14) and ad libitum or restricted (50% of previous 5-d intake; d 10 to 14) dry matter intake. Plasma was obtained 3 times daily on d 4, 8, and 12; milk samples were collected on d 8, 9, 13, and 14. Liver and muscle were biopsied on d 14 of each period. Free carnitine, short-chain acylcarnitine, and long-chain acylcarnitine concentrations were determined using a radioenzymatic assay coupled with ion exchange chromatography. Abomasal l-carnitine infusion increased total carnitine in plasma on d 8 and d 12. All liver carnitine fractions were increased by carnitine infusion. Feed restriction elevated concentrations of free carnitine, long-chain acylcarnitine, and total carnitine in liver tissue from carnitine-infused cows but not in those infused with water. In muscle, acid-soluble carnitine, long-chain acylcarnitine, and total carnitine concentrations were increased by carnitine infusion and feed restriction without significant interaction. Feed restriction increased free carnitine concentrations in muscle from water-infused cows but not in carnitine-infused cows. Carnitine infusion increased the concentration of each milk carnitine fraction as well as milk carnitine output on d 8 to 9. On d 13 to 14, all carnitine fractions except short-chain acylcarnitine were increased in milk from water-infused, feed-restricted cows, whereas all fractions were increased in carnitine-infused, feed-restricted cows. Carnitine infusion increased total carnitine in plasma, liver, muscle, and milk during feed restriction, whereas feed restriction alone increased carnitine concentrations in muscle and milk but not in liver. Liver carnitine concentrations might limit hepatic fatty acid oxidation capacity in dairy cows during the periparturient period; therefore, supplemental l-carnitine might decrease liver lipid accumulation in periparturient cows.

Impact of Oral Glycine Propionyl-L-Carnitine on Oxidative Stress, Antioxidant Status, and Exercise Performance

Various forms of L-carnitine have been shown to have antioxidant properties and to improve circulation and exercise performance in individuals with vascular disease, possibly mediated by enhanced nitric oxide production. PURPOSE: To compare the effects of a novel form of L-carnitine (glycine propionyl-L-carnitine {GPLC})to a placebo on markers of aerobic and anaerobic exercise performance, antioxidant status, oxidative stress, nitric oxide, and skeletal muscle carnitine content. METHODS: 32 healthy men or women (27±5 years) were randomly assigned in double-blind manner to receive either a placebo (n=9), GPLC at 1 g/d (n=12), or GPLC at 3g/d (n=11) in conjunction with an eight week program of supervised aerobic training. VO2peak, time to fatigue, and anaerobic threshold was assessed using a graded exercise treadmill test. Anaerobic power and work was assessed using a Wingate cycle test. Resting blood samples were analyzed for total whole blood glutathione, total plasma antioxidant capacity, and plasma nitric oxide. Muscle samples were analyzed for total, free, and acyl carnitine. All above variables were determined before and following the eight week intervention. Malondialdehyde (MDA) was measured pre and post both exercise tests; pre and post intervention. RESULTS: With the exception of a significant (P<0.05) increased anaerobic threshold for both GPLC groups (9-10%) compared to placebo (2%), no exercise performance effects were observed (p<0.05). While both glutathione and antioxidant status were higher in the GPLC groups compared to placebo, these differences were not statistically significant (P>0.05). The percent change for nitric oxide was statistically greater for GPLC 3g/d (55±15) compared to GPLC 1g/d (10±15) and placebo (7±17, P<0.05). Muscle carnitine content was maintained at 3g/d of GPLC, but decreased following training in the other groups. Resting MDA was decreased 22-30% in the GPLC groups compared to no change in the placebo group following the intervention, but the same pattern of change was present in all groups in response to both exercise tests (p<0.05). CONCLUSION: These findings indicate that GPLC supplementation may increase the anaerobic threshold, maintain muscle carnitine content at 3g/d, increase resting nitric oxide production, and decrease resting lipid peroxidation.

Ontogeny of Carnitine Palmitoyltransferase I Activity, Carnitine-Km, and mRNA Abundance in Pigs throughout Growth and Development 2

Carnitine palmitoyltransferase (CPT) I catalyzes an important regulatory step in lipid metabolism; however, no studies, to our knowledge, have evaluated the molecular and kinetic [maximal velocity and Michaelis constant (Km) for carnitine] ontogeny of CPT I and prevailing tissue concentrations of carnitine in pigs. To this end, hepatic and skeletal muscle tissues were examined at various ages: birth; 24 h; 1, 3, 5, and 8 wk of age; and adult. Hepatic and skeletal muscle CPT I specific activities were low at birth and increased 100 and 70%, respectively, during the first week of life (P < 0.05). Skeletal muscle transcript amounts were 2.7-fold greater (P < 0.001) in 24-h-old pigs relative to newborns, whereas hepatic CPT I mRNA remained constant at each age studied. The apparent Km for carnitine decreased 48% (P < 0.05) during the initial 3 wk of life in liver and decreased 40% (P < 0.05) during the first week of life in skeletal muscle. Plasma and liver free carnitine concentrations increased 95 and 62%, respectively, within 24 h after birth (P < 0.05) and hepatic carnitine concentrations remained constant through 5 wk of age. Consequently, hepatic carnitine concentrations were 20–80% greater (P < 0.05) than the Km for carnitine during the suckling period. Skeletal muscle carnitine met or exceeded the apparent Km for carnitine at each stage of development. Collectively, these findings suggest that postnatal increases in CPT I activity during the suckling period are accompanied by increased tissue carnitine; however, the lack of hepatic CPT I mRNA induction and low activity reported in both tissues prior to 1 wk of age may limit postnatal lipid utilization during the piglet’s transition to extra-uterine life.

Chicken liver and muscle carnitine palmitoyltransferase 1: Nutritional regulation of messengers

In mammals, carnitine palmitoyltransferase 1 (CPT1) is a rate limiting enzyme of fatty acid oxidation. Two isoforms are present. We characterized a full-length cDNA sequence encoding chicken liver L-CPT1 isoform and a partial cDNA sequence encoding chicken muscle M-CPT1 isoform. CPT1 messengers showed the expected tissue specificity. M-CPT1 messenger and CPT1 activity were higher in oxidative than in glycolytic muscle. Expression of both isoforms was assessed in various tissues of genetically fat or lean chickens. Fasting considerably increased L-CPT1 mRNA expression and β-hydroxyacyl CoA dehydrogenase (HAD) activity in the liver of fat or lean chickens. Unexpectedly, fasting did not increase M-CPT1 mRNA levels nor HAD activity in muscles of either chicken genotype. It however increased succinyl-CoA:3-ketoacid CoA transferase (SCOT) mRNA expression (an enzyme related to ketone body utilization) in oxidative muscle. SCOT messenger was slightly more abundant in oxidative muscle of lean chickens but not in glycolytic muscle. In conclusion, the regulation of fatty acid oxidation is probably not impaired in fat chicken. The absence of fasting stimulation of M-CPT1 mRNA expression, which is at variance with the situation observed in mammals, suggests that during fasting, chicken muscles preferentially use ketone bodies as fuel, at least in the short term.