Search results for "Carnitine"
showing 10 items of 96 documents
Mildronate, a Regulator of Energy Metabolism, Reduces Atherosclerosis in apoE/LDLR<sup>–/–</sup> Mice
2009
<i>Background/Aims:</i> Mildronate, an inhibitor of <i>L</i>-carnitine biosynthesis and transport, is used in clinics as a modulator of cellular energy metabolism and is a cardioprotective drug. <i>L</i>-Carnitine is a pivotal molecule in fatty acid oxidation pathways and its regulation in vasculature might be a promising approach for antiatherosclerotic treatment. This study was performed to evaluate the effects of mildronate treatment on the progression of atherosclerosis and the content of <i>L</i>-carnitine in the vascular wall. <i>Methods:</i> ApoE/LDLR<sup>–/–</sup> mice received mildronate at doses of 30 and 100 …
Beneficial effects of l-carnitine in myoblastic C2C12 cells
2003
L-Carnitine is a key molecule in the transfer of fatty acid across mitochondrial membranes. Bioavailable L-carnitine is either provided by an endogeneous biosynthesis or after intestinal absorption of dietary items containing L-carnitine. After intestinal absorption or hepatic biosynthesis, L-carnitine is transferred to organs whose metabolism is dependent upon fatty acid oxidation, such as skeletal muscle. To cross the muscle plasma membrane, there are several transporters involved. Among those transporters, OCTN2 is actually the only one to have been clearly characterized. Zidovudine is a commonly used inhibitor of human immunodeficiency virus (HIV) replication. Zidovudine has many side e…
Effects of γ-Butyrobetaine and Mildronate on Nitric Oxide Production in Lipopolysaccharide-Treated Rats
2008
Production of nitric oxide was measured in lipopolysaccharide-treated rats (10 mg/kg, 4 hr) using the electron paramagnetic resonance method. As compared to the control animals, the nitric oxide level in liver of lipopolysaccharide-treated rats increased from 27.6+/-4.7 to 1485+/-129 ng/g tissue, in heart from 4.8+/-0.7 to 271+/-26 ng/g tissue, in blood from 33.6+/-12.4 to 638+/-136 ng/g tissue, in kidney from 3.3+/-0.5 to 356+/-31 ng/g tissue, in brain cortex from 46.0+/-3.4 to 227+/-27 ng/g tissue, in cerebellum from 27.7+/-2.6 to 218+/-30 ng/g tissue, and in testes from 13.8+/-1.1 to 86+/-8 ng/g tissue. Administration of the antiischaemic drug, mildronate (120 mg/kg) caused a significant…
In vivo release of non-neuronal acetylcholine from the human skin as measured by dermal microdialysis: effect of botulinum toxin
2006
1.--Acetylcholine is synthesized in the majority of non-neuronal cells, for example in human skin. In the present experiments, the in vivo release of acetylcholine was measured by dermal microdialysis. 2.--Two microdialysis membranes were inserted intradermally at the medial shank of volunteers. Physiological saline containing 1 muM neostigmine was perfused at a constant rate of 4 microl min(-1) and the effluent was collected in six subsequent 20 min periods. Acetylcholine was measured by high-pressure liquid chromatography (HPLC) combined with bioreactors and electrochemical detection. 3.--Analysis of the effluent by HPLC showed an acetylcholine peak that disappeared, when the analytical c…
Regional differences of substrate oxidation capacity in rat hearts: effects of extra load and endurance training.
1990
Male rats, aged 17 weeks at the end of experiments, were divided into four groups. Two groups lived in normal cage conditions with or without extra load (20% of the body weight) and two groups were trained by running with or without extra load for 8 weeks. Oxidation rates of succinate, glutamate + malate, palmitoylcarnitine, and pyruvate, and the activities of lactate dehydrogenase, citrate synthase, isocitrate dehydrogenase and cytochrome oxidase were measured in homogenates of the right ventricle and in those of the subendocardial and subepicardial layers of the left ventricle. Oxidation rates of succinate and palmitoylcarnitine tended to be higher in the subendocardium than in the subepi…
Mboat7 down-regulation by hyper-insulinemia induces fat accumulation in hepatocytes.
2020
Background: Naturally occurring variation in Membrane-bound O-acyltransferase domain-containing 7 (MBOAT7), encoding for an enzyme involved in phosphatidylinositol acyl-chain remodelling, has been associated with fatty liver and hepatic disorders. Here, we examined the relationship between hepatic Mboat7 down-regulation and fat accumulation. Methods: Hepatic MBOAT7 expression was surveyed in 119 obese individuals and in experimental models. MBOAT7 was acutely silenced by antisense oligonucleotides in C57Bl/6 mice, and by CRISPR/Cas9 in HepG2 hepatocytes. Findings: In obese individuals, hepatic MBOAT7 mRNA decreased from normal liver to steatohepatitis, independently of diabetes, inflammatio…
Where Does Nε-Trimethyllysine for the Carnitine Biosynthesis in Mammals Come from?
2014
N(ε)-trimethyllysine (TML) is a non-protein amino acid which takes part in the biosynthesis of carnitine. In mammals, the breakdown of endogenous proteins containing TML residues is recognized as starting point for the carnitine biosynthesis. Here, we document that one of the main sources of TML could be the vegetables which represent an important part of daily alimentation for most mammals. A HPLC-ESI-MS/MS method, which we previously developed for the analysis of N(G)-methylarginines, was utilized to quantitate TML in numerous vegetables. We report that TML, believed to be rather rare in plants as free amino acid, is, instead, ubiquitous in them and at not negligible levels. The occurrenc…
Suppression of intestinal microbiota-dependent production of pro-atherogenic trimethylamine N-oxide by shifting L-carnitine microbial degradation.
2014
Abstract Aims Trimethylamine-N-oxide (TMAO) is produced in host liver from trimethylamine (TMA). TMAO and TMA share common dietary quaternary amine precursors, carnitine and choline, which are metabolized by the intestinal microbiota. TMAO recently has been linked to the pathogenesis of atherosclerosis and severity of cardiovascular diseases. We examined the effects of anti-atherosclerotic compound meldonium, an aza-analogue of carnitine bioprecursor gamma-butyrobetaine (GBB), on the availability of TMA and TMAO. Main methods Wistar rats received L-carnitine, GBB or choline alone or in combination with meldonium. Plasma, urine and rat small intestine perfusate samples were assayed for L-car…
The effects of carnitine on the growth of sea bass, Dicentrarchus labrax L., fry
1986
Carnitine treatment has an appreciable effect on the hatchery-reared sea bass, Dicentrarchus labrax, fry. The administration of the laevorotatory isomer (1-carnitine) which is engaged in the transport of the acyl and acetyl groups through the mitochondrial membrane, stimulating lipid metabolism, increases the growth rate and the protein content of the treated fry. The dextrorotatory isomer (d-carnitine), which is an antagonist of the 1-carnitine, has an opposite effect on the growth and metabolism of the treated fry.
Stilbenes and resveratrol metabolites improve mitochondrial fatty acid oxidation defects in human fibroblasts
2014
International audience; Background: Inborn enzyme defects of mitochondrial fatty acid beta-oxidation (FAO) form a large group of genetic disorders associated to variable clinical presentations ranging from life-threatening pediatric manifestations up to milder late onset phenotypes, including myopathy. Very few candidate drugs have been identified in this group of disorders. Resveratrol (RSV) is a natural polyphenol with anti-oxidant and anti-inflammatory effects, recently shown to have beneficial metabolic properties in mice models. Our study explores its possible effects on FAO and mitochondrial energy metabolism in human cells, which are still very little documented.Methods: Using cells …