L(-)-Carnitine CAS NO.541-15-1

L-carnitine exposure and mitochondrial function in human neuronal cells.[Pubmed: 24005823]

Neurochem Res. 2013 Nov;38(11):2336-41.

L-Carnitine inner salt is a naturally occurring substance required in mammalian energy metabolism that functions by facilitating long-chain fatty acid entry into cellular mitochondria, thereby delivering substrate for oxidation and subsequent energy production. It has been purposed that L-Carnitine inner salt may improve and preserve cognitive performance, and may lead to better cognitive aging through the life span, and several controlled human clinical trials with L-Carnitine inner salt support the hypothesis that this substance has the ability to improve cognitive function. We further hypothesized that, since L-Carnitine inner salt is an important co-factor of mammalian mitochondrial energy metabolism, acute administration of L-Carnitine inner salt to human tissue culture cells should result in detectable increases in mitochondrial function.
METHODS AND RESULTS:
Cultures of SH-SY-5Y human neuroblastoma and 1321N1 human astrocytoma cells grown in 96-well cell culture plates were acutely administered L-Carnitine inner salt hydrochloride, and then, mitochondrial function was assayed using the colorimetric 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt cell assay kit in a VERSAmax tunable microplate reader. Significant increases in mitochondrial function were observed when human neuroblastoma or human astrocytoma cells were exposed to 100 nM (20 μg L-Carnitine inner salt hydrochloride/L) to 100 μM (20 mg L-Carnitine inner salt hydrochloride/L) concentrations of L-Carnitine inner salt hydrochloride in comparison to unexposed cells, whereas no significant positive effects were observed at lower or higher concentrations of L-Carnitine inner salt hydrochloride.
CONCLUSIONS:
The results of the present study provide insights for how L-Carnitine inner salt therapy may significantly improve human neuronal function, but we recommend that future studies further explore different derivatives of L-Carnitine inner salt compounds in different in vitro cell-based systems using different markers of mitochondrial function.

L-Carnitine intake prevents irregular feeding-induced obesity and lipid metabolism disorder.[Pubmed: 25445284]

Gene. 2015 Jan 10;554(2):148-54.

L-Carnitine inner salt supplementation has been used to reduce obesity caused by high-fat diet, which is beneficial for lowering blood and hepatic lipid levels, and for ameliorating fatty liver. However, whether L-Carnitine inner salt may affect irregular feeding-induced obesity and lipid metabolism disorder is still largely unknown.
METHODS AND RESULTS:
In the present study, we developed a time-delayed pattern of eating, and investigated the effects of L-Carnitine inner salt on the irregular eating induced adiposity in mice. After an experimental period of 8 weeks with L-Carnitine inner saltsupplementation, L-Carnitine inner salt significantly inhibited body weight increase and epididymal fat weight gain induced by the time-delayed feeding. In addition, L-Carnitine inner saltadministration decreased levels of serum alanine aminotransferase (GPT), glutamic oxalacetic transaminase (GOT) and triglyceride (TG), which were significantly elevated by the irregular feeding. Moreover, mice supplemented with L-Carnitine inner salt did not display glucose intolerance-associated hallmarks, which were found in the irregular feeding-induced obesity. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that L-Carnitine inner salt counteracted the negative alterations of lipid metabolic gene expression (fatty acid synthase, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, cholesterol 7α-hydroxylase, carnitine/acylcarnitine translocase) in the liver and fat of mice caused by the irregular feeding.
CONCLUSIONS:
Therefore, our results suggest that the time-delayed pattern of eating can induce adiposity and lipid metabolic disorders, while L-Carnitine inner salt supplementation might prevent these negative symptoms.

Characterization of L-carnitine transport into rat skeletal muscle plasma membrane vesicles.[Pubmed: 10727937]

Eur J Biochem. 2000 Apr;267(7):1985-94.

METHODS AND RESULTS:
Transport of L-Carnitine inner salt into skeletal muscle was investigated using rat sarcolemmal membrane vesicles. In the presence of an inwardly directed sodium chloride gradient, L-Carnitine inner salt transport showed a clear overshoot. The uptake of L-Carnitine inner salt was increased, when vesicles were preloaded with potassium. When sodium was replaced by lithium or cesium, and chloride by nitrate or thiocyanate, transport activities were not different from in the presence of sodium chloride. However, L-Carnitine inner salt transport was clearly lower in the presence of sulfate or gluconate, suggesting potential-dependent transport. An osmolarity plot revealed a positive slope and a significant intercept, indicating transport of L-Carnitine inner salt into the vesicle lumen and binding to the vesicle membrane. Displacement experiments revealed that approximately 30% of the L-Carnitine inner salt associated with the vesicles was bound to the outer and 30% to the inner surface of the vesicle membrane, whereas 40% was unbound inside the vesicle. Saturable transport could be described by Michaelis-Menten kinetics with an apparent Km of 13.1 microM and a Vmax of 2.1 pmol.(mg protein-1).s-1. L-Carnitine inner salt transport could be trans-stimulated by preloading the vesicles with L-Carnitine inner salt but not with the carnitine precursor butyrobetaine, and was cis-inhibited by L-palmitoylcarnitine, L-isovalerylcarnitine, and glycinebetaine. On comparing carnitine transport into rat kidney brush-border membrane vesicles and OCTN2, a sodium-dependent high-affinity human carnitine transporter, cloned recently from human kidney also expressed in muscle, the Km values are similar but driving forces, pattern of inhibition and stereospecificity are different.
CONCLUSIONS:
This suggests the existence of more than one carnitine carrier in skeletal muscle.

L-carnitine enhances axonal plasticity and improves white-matter lesions after chronic hypoperfusion in rat brain.[Pubmed: 25465043]

J Cereb Blood Flow Metab. 2015 Mar;35(3):382-91.

Chronic cerebral hypoperfusion causes white-matter lesions (WMLs) with oxidative stress and cognitive impairment. However, the biologic mechanisms that regulate axonal plasticity under chronic cerebral hypoperfusion have not been fully investigated.
METHODS AND RESULTS:
Here, we investigated whether L-Carnitine inner salt, an antioxidant agent, enhances axonal plasticity and oligodendrocyte expression, and explored the signaling pathways that mediate axonal plasticity in a rat chronic hypoperfusion model. Adult male Wistar rats subjected to ligation of the bilateral common carotid arteries (LBCCA) were treated with or without L-Carnitine inner salt. L-Carnitine inner salt-treated rats exhibited significantly reduced escape latency in the Morris water maze task at 28 days after chronic hypoperfusion. Western blot analysis indicated that L-Carnitine inner salt increased levels of phosphorylated high-molecular weight neurofilament (pNFH), concurrent with a reduction in phosphorylated phosphatase tensin homolog deleted on chromosome 10 (PTEN), and increased phosphorylated Akt and mammalian target of rapamycin (mTOR) at 28 days after chronic hypoperfusion. L-Carnitine inner salt reduced lipid peroxidation and oxidative DNA damage, and enhanced oligodendrocyte marker expression and myelin sheath thickness after chronic hypoperfusion.
CONCLUSIONS:
L-Carnitine inner salt regulates the PTEN/Akt/mTOR signaling pathway, and enhances axonal plasticity while concurrently ameliorating oxidative stress and increasing oligodendrocyte myelination of axons, thereby improving WMLs and cognitive impairment in a rat chronic hypoperfusion model.