• Title/Summary/Keyword: L-Carnitine

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Cydonia oblonga Miller fruit extract exerts an anti-obesity effect in 3T3-L1 adipocytes by activating the AMPK signaling pathway

  • Hyun Sook Lee;Jae In Jung;Jung Soon Hwang;Myeong Oh Hwang;Eun Ji Kim
    • Nutrition Research and Practice
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    • v.17 no.6
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    • pp.1043-1055
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    • 2023
  • BACKGROUND/OBJECTIVES: The fruit of Cydonia oblonga Miller (COM) is used traditionally in Mediterranean region medicine to prevent or treat obesity, but its mechanism of action is still unclear. Beyond a demonstrated anti-obesity effect, the fruit was tested for the mechanism of adipogenesis in 3T3-L1 preadipocytes. MATERIALS/METHODS: 3T3-L1 preadipocytes were cultured for 8 days with COM fruit extract (COME) at different concentrations (0-600 ㎍/mL) with adipocyte differentiation medium. The cell viability was measured using an MTT assay; triglyceride (TG) was stained with Oil Red O. The expression levels of the adipogenesis-related genes and protein expression were analyzed by reverse transcription polymerase chain reaction and Western blotting, respectively. RESULTS: COME inhibited intracellular TG accumulation during adipogenesis. A COME treatment in 3T3-L1 cells induced upregulation of the adenosine monophosphate-activated protein kinase (AMPK)α phosphorylation and downregulation of the adipogenic transcription factors, such as sterol regulatory element-binding protein 1c, peroxisome proliferator-activated receptor γ, and CCAAT/enhancer binding protein α. The COME treatment reduced the mRNA expression of fatty acyl synthetase, adenosine triphosphate-citrate lyase, adipocyte protein 2, and lipoprotein lipase. It increased the mRNA expression of hormone-sensitive lipase and carnitine palmitoyltransferase I in 3T3-L1 cells. CONCLUSIONS: COME inhibits adipogenesis via the AMPK signaling pathways. COME may be used to prevent and treat obesity.

Long-Term Follow Up of Refractory Myotonia Associated with Hyperadrenocorticism in a Maltese Dog

  • Nam, Sookin;Kang, Byeong-Teck;Song, Kun-ho;Seo, Kyoung-won
    • Journal of Veterinary Clinics
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    • v.37 no.5
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    • pp.273-277
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    • 2020
  • A 12-year-old, female Maltese was referred with uncontrolled hyperadrenocorticism (HAC). Despite well management of HAC through treatment with trilostane and serial monitoring with ACTH stimulation tests for over three years, stiffness of the neck and limbs progressively worsened over time. Neurological test was performed, which showed no abnormalities of cranial nerves. Proprioception was delayed but the cause appeared to be due to stiffness of limb muscles. Muscle tone had increased over time and stiffness had worsened to the extent where it made walking difficult. MRI scans showed no orthopedic or spinal diseases, and pituitary microadenoma was confirmed with pituitary gland measurement of 6 × 6.4 × 4.5 mm (H × W × L). Electromyography presented random discharges with fluctuating amplitude and frequency, which were consistent with myotonic discharges. There were no improvements of myotonic signs despite treatment for HAC with trilostane. Supplementation of L-carnitine and coenzyme Q-10 to mitigate muscle stiffness, following diazepam and methocarbamol to help with muscle rigidity, failed to show any positive effect and the dog died a sudden death, 1,182 days after the initial visit.

Twenty-one-year follow-up of variable onset MELAS syndrome with heteroplasmic nt3243A>G mtDNA mutation: A case report

  • Song, Wung Joo;Lee, Yoon Jin;Kang, Joon Won;Chang, Mea Young;Song, Kyu Sang;Kang, Dae Young;Kim, Sook Za
    • Journal of Genetic Medicine
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    • v.16 no.1
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    • pp.31-38
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    • 2019
  • Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a maternally inherited mitochondrial disorder of which m.3243A>G is the most commonly associated mutation, resulting in an inability to meet the energy requirements of various organs. MELAS poses a diagnostic challenge owing to its multiple organ involvement and great clinical variability due to its heteroplasmic nature. We report three cases from a family who were initially misdiagnosed with myasthenia gravis or undiagnosed. Although there is no optimal consensus treatment approach for patients with MELAS because of the disease's heterogeneity, our 21-year-long therapy regimen of ${\text\tiny{L}}-arginine$, ${\text\tiny{L}}-carnitine$, and coenzyme Q10 supplementation combined with dietary management appeared to provide noticeable protection from the symptoms and complications. Prompt early diagnosis is important, as optimal multidisciplinary management and early intervention may improve outcomes.

HPLC Determination and Pharmacokinetics of Endogenous Acetyl-L-Carnitine (ALC) in Human Volunteers Orally Administered a Single Dose of ALC

  • Kwon, Oh-Seung;Chung, Youn-Bok
    • Archives of Pharmacal Research
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    • v.27 no.6
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    • pp.676-681
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    • 2004
  • Acetyl-L-camitine (ALC), a naturally occurring endogenous compound, has been shown to improve the cognitive performance of patients with senile dementia Alzheimer's type, and to be involved in cholinergic neurotransmission. Because ALC is an endogenous compound, valida-tion of the analytical methods of ALC in the biological fluids is very important and difficult. This study was presented validation and correction for plasma ALC concentrations and pharmacok-inetics after oral administration of ALC to human volunteers. ALC concentrations in human plasma were corrected by subtracting the concentration of blank plasma from each sample. Precision and accuracy (bias %) for uncorrected ALC concentrations were below 2.6 and 6.5% for intra-days, and 4.0 and 9.4% for inter-days, respectively. Precision and accuracy (bias %)for corrected ALC concentrations were below 10.9 and 6.0% for intra-days, and 10.5 and 16.9% for inter-days, respectively. Quantitation limit was $0.1{\;}\mu\textrm{g}/mL$. After oral administration of a 500 mg ALC tablet to 8 healthy volunteers, the principle pharmacokinetic parameters were 4.2 h of the half-life$ (t_{1/2},{\beta})$, the area under the curve $(AUC_{0{\rightarrow}8){\;}of{\;}9.88{\;}\mu\textrm{g}{\cdot}h/mL$, and 3.1 h of the time ($T_{max}$) to reach $C_{max}$. This study first describes the pharmacokinetic study after oral admin-istration of a single dose of ALC in human volunteers.

Alterations of Heart Rate Variability upon β3-Adrenergic Receptor Polymorphism and Combined Capsaicin, Sesamin, and L-Carnitine in Humans (복합 캡사이신, 세사인, 그리고 카르니틴과 베타3 유전자 다형에 대한 심박수 변이성의 영향)

  • Shin, Ki-Ok;Kim, Hyun-Jun;Kang, Sung-Hwun
    • Journal of Life Science
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    • v.18 no.3
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    • pp.291-297
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    • 2008
  • We investigated whether 1) the combined capsaicin (75 mg), sesamin (30 mg), and L-carnitine (900 mg) (CCSC) ingestion enhances autonomic nervous system (ANS) activities including thermogenic sympathetic activity as energy metabolic modulator, 2) ${\beta}_3-AR$ polymorphism of each subject influences with ANS activity. Seven healthy males $(22.0{\pm}0.5\;yr)$ volunteered for this study. The cardiac autonomic nervous activities evaluated by means of heart rate variability of power spectral analysis were continuously measured during 5 min every 30 min for total 120 min resting condition with CCSC or placebo oral administration chosen at random. The results indicated that, there are not $Arp/Arg^{64}$ variants of the ${\beta}_3-AR$ genotypes in our subjects. There were not also significant differences in heart rate during rest between both trials. The difference of ANS activity did not reach the statistical significance between both trials. However, the significant improvement showed TOTAL power, HF component, and the indices of SNS and PNS activities before and at 30 min after CCSC ingestion (p<0.05, respectively). In conclusions, although each component of combined CCSC is associated with lipolysis and/or fat oxidation, the combined CCSC consumption is not influenced in stimulation of thermogenic sympathetic activity as modulator of energy metabolism. In rather, our results suggested that CCSC ingestion improves the balance of both SNS and PNS activities. Therefore, it will be considered many combined nutrient components for ergogenic and/or lipolysis effects as well as genetic variants affecting ANS activity in further studies.

Effects of Various Nootropic Candidates on the Impaired Acquisition of Ethanol-treated Rats in Step-through Test (에탄올 급성 투여로 유발된 학습획득 손상에 미치는 수종 뇌기능개선 후보 물질의 작용)

  • Lee Soon-Chul;Kim Eun-Joo;You Kwan-Hee;Kang Jong-Seong;Moon Yang-Sun
    • Journal of Ginseng Research
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    • v.23 no.2 s.54
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    • pp.115-121
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    • 1999
  • Effects of single and repeated administration of various nootropic candidates were examined on impaired acquisition by single oral administration of 3 g/kg ethanol (EtOH) in step through test. The inhibitory effect of EtOH on acquisition was significantly reduced by single picrotoxin, but not affected by diazepam, acetyl-L-carnitine and apomorphine. Single or repeated red ginseng total saponin and deprenyl, single piracetam, repeated N-methyl-D-glucamine, but not single or repeated protopanaxadiol, protopanaxatriol and centrophenoxine significantly ameliorated the impairment of acquisition by EtOH. On the other hand, the inhibitory effect of repeated red ginseng total saponin but not that of repeated N-methyl-D-Glucamine, was significantly blocked by pretreatment of $\alpha$-methyl-$\rho$-tyrosine, a inhibitor of catecholamine synthesis. Whereas, the inhibitory effect of repeated deprenyl on EtOH amnesia was exaggerated by $\alpha$-methyl-$\rho$-tyrosine. These results suggest that the amelioration processes of drugs on ethanol amnesia involve complex mechanism between the central GABAergic and dopaminergic neuronal activity in memory and learning, although the effects of repeated drugs administration are not yet clear.

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Effect of reduced energy density of close-up diets on metabolites, lipolysis and gluconeogenesis in Holstein cows

  • Huang, Wenming;Wang, Libin;Li, Shengli;Cao, Zhijun
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.5
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    • pp.648-656
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    • 2019
  • Objective: An experiment was conducted to determine the effect of reduced energy density of close-up diets on metabolites, lipolysis and gluconeogenesis in cows during the transition period. Methods: Thirty-nine Holstein dry cows were blocked and assigned randomly to three groups, fed a high energy density diet (HD, 1.62 Mcal of net energy for lactation $[NE_L]/kg$ dry matter [DM]), a medium energy density diet (MD, $1.47Mcal\;NE_L/kg\;DM$), or a low energy density diet (LD, $1.30Mcal\;NE_L/kg\;DM$) prepartum; they were fed the same lactation diet to 28 days in milk (DIM). All the cows were housed in a free-stall barn and fed ad libitum. Results: The reduced energy density diets decreased the blood insulin concentration and increased nonesterified fatty acids (NEFA) concentration in the prepartum period (p<0.05). They also increased the concentrations of glucose, insulin and glucagon, and decreased the concentrations of NEFA and ${\beta}-hydroxybutyrate$ during the first 2 weeks of lactation (p<0.05). The plasma urea nitrogen concentration of both prepartum and postpartum was not affected by dietary energy density (p>0.05). The dietary energy density had no effect on mRNA abundance of insulin receptors, leptin and peroxisome proliferator-activated $receptor-{\gamma}$ in adipose tissue, and phosphoenolpyruvate carboxykinase, carnitine palmitoyltransferase-1 and peroxisome proliferator-activated $receptor-{\alpha}$ in liver during the transition period (p>0.05). The HD cows had higher mRNA abundance of hormone-sensitive lipase at 3 DIM compared with the MD cows and LD cows (p = 0.001). The mRNA abundance of hepatic pyruvate carboxy-kinase at 3 DIM tended to be increased by the reduced energy density of the close-up diets (p = 0.08). Conclusion: The reduced energy density diet prepartum was effective in controlling adipose tissue mobilization and improving the capacity of hepatic gluconeogenesis postpartum.

In Vitro Anti-Obesity Effects of Raw Garlic and Pickled Garlic (생 마늘과 절인 마늘의 In Vitro 항비만 효과)

  • Lee, Da-Bin;Pyo, Young-Hee
    • Journal of Korean Medicine for Obesity Research
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    • v.21 no.2
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    • pp.69-79
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    • 2021
  • Objectives: This study aimed to compare the anti-obesity effects of raw and pickled garlic in vitro in 3T3-L1 preadipocytes. Methods: The pickled garlic samples comprised the following: garlic aged in vinegar (VG), garlic aged in soy sauce, and vinegar (1:1, v/v) (PG) and raw garlic (RG) as control. Hexane, butanol, and distilled water were used to prepare the fractions. The pancreatic lipase inhibitory activity was used as a measure of anti-obesity effects of the extracts. The lipid droplet accumulation and triglyceride content in the 3T3-L1 cells were measured using Oil red O staining and triglyceride assay kits, respectively. The adipogenesis related protein expression levels were analyzed using the kits and the western blot method. Results: The pancreatic lipase inhibitory activity of the garlic extracts (VG, PG, RG) was the highest in the butanol fraction, and the inhibitory effect was the highest in RG, followed by PG and VG. All garlic butanol extracts suppressed triglyceride accumulation in differentiated adipocytes (P<0.05) through the activation of cyclic adenosine monophosphate (AMP), AMP-activated protein kinase, carnitine palmitoyl transferase-1, and the inhibition of fatty acid synthase. Raw garlic extracts significantly inhibited the expression of proteins involved in adipogenesis as compared to pickled garlic. Conclusions: Raw garlic has the potential to be an effective natural material for reducing obesity compared to pickled garlic with vinegar or soy sauce.

Production of (R)-Ethyl-4-Chloro-3-Hydroxybutanoate Using Saccharomyces cerevisiae YOL151W Reductase Immobilized onto Magnetic Microparticles

  • Choo, Jin Woo;Kim, Hyung Kwoun
    • Journal of Microbiology and Biotechnology
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    • v.25 no.11
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    • pp.1810-1818
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    • 2015
  • For the synthesis of various pharmaceuticals, chiral alcohols are useful intermediates. Among them, (R)-ethyl-4-chloro-3-hydroxybutanoate ((R)-ECHB) is an important building block for the synthesis of L-carnitine. (R)-ECHB is produced from ethyl-4-chloro-3-oxobutanoate (ECOB) by a reductase-mediated, enantioselective reduction reaction. The Saccharomyces cerevisiae YOL151W reductase that is expressed in Escherichia coli cells exhibited an enantioselective reduction reaction toward ECOB. By virtue of the C-terminal His-tag, the YOL151W reductase was purified from the cell-free extract using Ni2+-NTA column chromatography and immobilized onto Ni2+-magnetic microparticles. The physical properties of the immobilized reductase (Imm-Red) were measured using electron microscopy, a magnetic property measurement system, and a zeta potential system; the average size of the particles was approximately 1 μm and the saturated magnetic value was 31.76 emu/g. A neodymium magnet was used to recover the immobilized enzyme within 2 min. The Imm-Red showed an optimum temperature at 45℃ and an optimum pH at 6.0. In addition, Bacillus megaterium glucose dehydrogenase (GDH) was produced in the E. coli cells and was used in the coupling reaction to regenerate the NADPH cofactor. The reduction/oxidation coupling reaction composed of the Imm-Red and GDH converted 20 mM ECOB exclusively into (R)-ECHB with an e.e.p value of 98%.

Role of certain nutritional supplements and biological regulators in the epilepsy

  • Asif, Mohammad
    • CELLMED
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    • v.3 no.4
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    • pp.29.1-29.11
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    • 2013
  • Certain dietary contents, biological supplements might influence the occurrence or treatment of epilepsy. Some studies have found that the supplementation with individual nutrients reduced seizure frequency or improved other aspects of health in patients with epilepsy. Potentially beneficial dietary interventions include treating blood glucose dysregulations. Identifying and avoiding allergenic foods, and avoiding suspected triggering agents such as alcohol, aspartame, and monosodium glutamate. The Atkins diet (very low in carbohydrates) is a less restrictive type diet that may be effective in some cases. Nutrients that may reduce seizure frequency include vitamin B6, magnesium, vitamin E, manganese, taurine, dimethylglycine, and omega-3 fatty acids. Administration of thiamine may improve cognitive function in patients with epilepsy. Supplementation with folic acid, vitamin B6, biotin, vitamin D, and L-carnitine may be needed to prevent or treat deficiencies resulting from the use of anticonvulsant drugs. Vitamin K1 has been recommended near the end of pregnancy for women taking anticonvulsants. Melatonin may reduce seizure frequency in some cases, and progesterone may be useful for women with cyclic exacerbations of seizures. In most cases, nutritional therapy is not a substitute for anticonvulsant medications. However, in selected cases, depending on the effectiveness of the interventions, dosage reductions or discontinuation of medications may be possible. However, nutrient supplementation may be necessary to prevent or reverse the effects of certain deficiencies that frequently result from the use of antiepileptic drugs.