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Substrate uptake and metabolism are preserved in hypertrophic caveolin-3 knockout hearts.

Caveolin-3 (Cav3), the primary protein component of caveolae in muscle cells, regulates numerous signaling pathways including insulin recept … R analysis revealed normal expression of lipid metabolism genes including FA translocase (CD36) and carnitine palmitoyl transferase-1 in Cav3KO hearts. Interestingly, myocardial cAMP content was significantly increased by 42%; however, this had no effect on PKA activity in Cav3KO hearts. Microarray expression analysis revealed a marked increase in the expre …

Interstitial deletion of 1p22.2p31.1 and medium-chain acyl-CoA dehydrogenase deficiency in a patient with global developmental delay.

We report on a 6-year-old girl who presented at 6 months of age with seizures, delayed psychomotor development and mild facial dysmorphism. A small muscular ventricular septal defect was documented on echocardiogram and brain MRI showed a frontal brain anomaly. Urine organic acid analysis revealed dicarboxylic aciduria, and plasma acylcarnitine analysis showed marked elevation of octanoyl (C8) and decanoyl (C10) carnitines with C8:C10 ratio of 9:1. These results were indicative of medium chain acyl-CoA dehydrogenase deficiency. ACADM gene sequencing showed an apparent homozygous c.166G > C (Al…

Myopathic dropped head syndrome: an expanding clinicopathological spectrum.

OBJECTIVE: A number of neuromuscular conditions may lead to a dropped head syndrome (DHS), with some patients developing a late onset noninf … ties in NADH dehydrogenase-reacted sections (6/7), desmin-positive sarcoplasmic deposits (1/7), low carnitine levels by biochemical assays (2/7), and mitochondrial changes (3/7). CONCLUSIONS: Myopathic DHS encompasses a wide spectrum of conditions that strongly affect NEM; however, as documented in the monozygotic twins, some patients may suffer from a dis …

Vitamin A deficiency modifies lipid metabolism in rat liver.

Liver fatty acid metabolism of male rats fed on a vitamin A-deficient diet for 3 months from 21 d of age was evaluated. Vitamin A restrictio … reased by 30 % of the control value and it was attributed to a high activity and mRNA expression of carnitine palmitoyltransferase-I (CPT-I). An increase in serum beta-hydroxybutyrate levels was observed in vitamin A-deficient rats. Vitamin A deficiency alters the mitochondria lipid composition and also enhances fatty acid oxidation by modifying the product …

Pancreatitis associated with hyperlipoproteinaemia type I in mink (Mustela vison): earliest detectable changes occur in mitochondria of exocrine cells.

Pancreatic tissue from young mink homozygous for a mutation in the lipoprotein lipase gene was studied by light and electron microscopy, wit … e necrosis was rapidly followed by inflammatory reactions. The activity of the mitochondrial enzyme carnitine O-palmitoyltransferase, essential for the transport of fatty acids into the mitochondria, was lower in the pancreas than in the liver. The activity of the peroxisomal fatty acid beta-oxidation was high in the liver and low in the pancreas of both li …

Pharmacologic therapy for HIV-associated lipodystrophy.

OBJECTIVE: To evaluate the efficacy and safety of pharmacologic therapy in the treatment of HIV-associated lipodystrophy, with a focus on th … ive in correcting body compositional changes associated with lipodystrophy. Anabolic steroids and l-carnitine are not effective in the treatment of lipodystrophy. CONCLUSIONS: No drug therapy exists to fully ameliorate or correct the cosmetic changes of HIV-associated lipodystrophy. Clinicians must weigh the benefits and risks of each agent and individuali …

Hepatotoxicity of commonly used drugs: nonsteroidal anti-inflammatory drugs, antihypertensives, antidiabetic agents, anticonvulsants, lipid-lowering agents, psychotropic drugs.

Hepatotoxic adverse drug reactions have contributed to the decline of many promising therapies, even among mainstream medication classes (br … abolite syndrome, delineation of the risk factors for valproic acid toxicity, the potential role of carnitine in preventing valproic acid hepatotoxicity, and the toxicity of second-line antiepileptic drugs. Liver injury associated with newer psychotropic agents, particularly the selective serotonin reuptake inhibitors, is also discussed. The focus of the re …

Meeting the challenges of a new millennium: optimizing the use of recombinant human erythropoietin.

Optimizing the use of recombinant human erythropoietin (r-HuEPO) involves choosing an appropriate dose regimen and target haemoglobin level, … se factors should be identified and corrected where possible. Ascorbic acid, vitamin D, folic acid, carnitine, other cytokines and growth factors have all been shown to augment the response to r-HuEPO in some patients. Further research is required before any of these adjuvant therapies can be incorporated into routine clinical practice. With regard to targe …

Altered hepatic gene expression in fecal peritonitis: changes in transcription of gluconeogenic, beta-oxidative, and ureagenic genes.

Sepsis alters energy production and utilization by the liver. Changes in both metabolic pathways that produce substrate (gluconeogenesis or … tion analysis, the steady-state levels of phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, carnitine palmitoyl transferase II, acetyl coenzyme A-acyltransferase, and ornithine transcarbamylase mRNAs were determined. Using transcript elongation analysis, the rate of transcription of each gene was investigated. Relative to control, steady-state mRNA …

The clinical spectrum of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.

Four patients with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency are presented. Clinical onset in the form of acute encephalopathy occurred between the ages of 9 months and 3 years. The clinical course included recurrent metabolic crises in 4 patients, cardiac involvement and retinopathy in 3, and myopathy in 2. None had signs of peripheral neuropathy. Three patients died and one is currently well. Hypoketotic hypoglycemia with C6-C14 3-hydroxy-dicarboxylic aciduria during metabolic crises associated with decreased plasma carnitine levels was the main biochemical finding. Enzymo…

[Hypertrophic cardiomyopathy caused by cytochrome-oxidase deficiency].

Mitochondrial cytopathies are due to genetic anomalies in the oxidative phosphorylation enzymes (excepting Krebs cycle, pyruvate and certain … ria from a peripheral muscle biopsy. Treatment with riboflavin, ascorbic acid, factor P, menadione, carnitine and iron sulfate has currently provided some symptomatic improvement. In patients with unexplained cardiomyopathy, the diagnosis of mitochondrial cytopathy should be entertained if oxidoreduction potentials (lactate/pyruvate ratio) are perturbed. Th …

Control of the cardiac consequences of myocardial ischemia and reperfusion by L-propionylcarnitine: age-response and dose-response studies in the rat heart.

We assessed the protective effects of L-propionylcarnitine, a liposoluble analogue of carnitine, in the isolated heart from rats of different ages subjected to global ischemia and reperfusion. Hearts from neonatal (3- to 7-d-old), immature (2- to 3-wk-old), and adult rats were retrogradely perfused with a modified Krebs bicarbonate buffer and subjected to ischemia and reperfusion. L-Pro-pionylcarnitine was given either before ischemia and throughout reperfusion (protocol 1) or during reperfusion only (protocol 2). Coronary flow, heart rate, left ventricular developed pressure, and left ventric…

From the National Institute of Allergy and Infectious Diseases: Summary of a workshop on disease mechanisms and prospects for prevention of Reye's syndrome.

The workshop participants identified several areas that are worthy of investigation. A better understanding of the populations at risk is ne … metabolic risk factor or the possibility of a common environmental risk factor. Further studies of carnitine metabolism would be appropriate in this regard. Third, epidemiologic experience with Reye's syndrome suggests that clusters of cases may occur more frequently when new influenza A or B viruses become epidemic. This pattern was observed most clearly …

The uptake and release of calcium by heart mitochondria.

The kinetics of uptake of Ca(2+) by rat heart mitochondria were studied by a spectrophotometric method with Arsenazo III indicator. The expo … is accompanied by a gradual decrease in internal ATP; it is initiated by palmitoyl-CoA (reversed by carnitine), by lysophosphatidylcholine, by Na(+) salts (reversed by oligomycin) and by K(+) salts added to a K(+)-free medium containing valinomycin. The process is probably a response to an increased energy load imposed on the mitochondria by the various con …

Case Report: When metabolism meets malabsorption: Imerslund-Gräsbeck syndrome with coexisting propionic acidemia presenting as recurrent metabolic crises.

BACKGROUND: Propionic acidemia and Imerslund-Gräsbeck syndrome are rare inherited metabolic disorders with distinct pathophysiological mecha … tropenia, microcytic anemia, and persistent proteinuria. Metabolic workup showed elevated propionyl carnitine with increased urinary 3-hydroxypropionic acid and propionyl glycine, suggestive of propionic acidemia. Whole-exome sequencing identified a homozygous pathogenic variant in the PCCB gene, confirming propionic acidemia, along with a novel homozygous …

High-altitude hypoxia remodels lipid metabolism in renal tubular epithelial cells by inhibiting the expression of HNF4α.

A deficiency of fatty acid oxidation (FAO) is the key hallmark in renal tubular epithelial cells (TECs) under high-altitude hypoxia (HH), re … and enhanced apoptosis. Mechanistically, HNF4α directly activates ACOX1 transcription and modulates Carnitine Palmitoyltransferase1A (CPT1A) expression, thereby enhancing FAO capacity. This leads to reduced reactive oxygen species (ROS) accumulation, improved mitochondrial membrane potential, and promoted ATP synthesis, ultimately mitigating hypoxia-related …

Dietary glycerol partially replaces excess lipids in the diet of GIFT tilapia (Oreochromis niloticus) under hyperthermal stress conditions.

The study evaluated dietary glycerol as a lipid substitute for genetically improved farmed tilapia (GIFT, Oreochromis niloticus) juveniles r … lipid catabolism, characterized by increased lipolytic markers (muscle lipoprotein lipase, hepatic carnitine palmitoyltransferase I, and peroxisome proliferator-activated receptor alpha gene expression) while decreased lipogenic indicators (hepatic glucose-6-phosphate dehydrogenase, malic enzyme, and fatty acid synthase gene expression). Histological analy …

CPT1A alters granulosa cell proliferation and steroidogenic activity in association with fatty acid oxidation during goat follicular development.

Follicular development in goats relies on the extensive proliferation and hormone synthesis of granulosa cells (GCs), processes that require an adequate energy supply. Fatty acid oxidation (FAO) represents a primary energy source for granulosa cells. However, how its rate-limiting enzyme, carnitine palmitoyltransferase 1A (CPT1A), modulates granulosa cell function remains unclear. This study examined CPT1A expression in healthy and atretic follicles and investigated its association with FAO-associated gene expression, ATP generation, proliferation, steroidogenesis, and palmitic acid (PA)-induc…

Acetyl-CoA metabolism in skeletal biology and bone disorders: From mechanisms to therapeutic implications.

Acetyl-CoA is a central metabolite that links energy status to transcriptional regulation through protein acetylation, yet its functions in skeletal biology depend strongly on subcellular compartmentalization. Because acetyl-CoA does not freely traverse biological membranes, its mitochondrial, cytosolic, and nuclear pools are maintained through compartment-specific synthesis and exchange routes, including the citrate-SLC25A1-ACLY axis, acetylcarnitine/carnitine cycling, acetate-dependent ACSS2 activity, and local nuclear enzyme activity. This review synthesizes current evidence that three cons…

Метаболомический атлас вируса денге обнаруживает явные биоактивные липидные сигнатуры.

Вирус Денга (DENV), похоже, манипулирует несколькими клеточными метаболическими путями, чтобы позволить им воспроизвести его и иммунное уклонение в носителе. Здесь мы использовали масс-спектрометрию высокого разрешения (HR-MS) для исследования сыворотки метаболомного ландшафта клинической инфекции DENV. Для нецелевой метаболомической количественной оценки на Waters Xevo G2-XS QTof Mass Spectromeme были использованы образцы серума из первичного денге (n = 11), вторичного денге (n = 9) проб и здорового контроля (n = 10). Была проведена оценка обязательного потенциала отдельных лигандов против DE

Совпадение в аннотации оригинала
Dengue virus (DENV) appears to manipulate several cellular metabolic pathways to permit its replication and immune evasion in the host. Here … pids, phosphatidylcholines, phosphatidylserines, and phosphatidylinositols, were detected alongside carnitine fragments, ceramides, diacylglycerols (DAGs), and bile acid conjugates in dengue. Molecular docking showed that DAG consistently exhibited strong binding to all the DENV proteins. Notably, lysophosphatidylcholine (LPC) 22:6 showed a selectively stro …