• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.2
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• pp.39-47
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• 2017

Purpose: A sensitive gas chromatography mass spectrometry (GC-MS) method was developed for screening of fatty acid oxidation disorders. Methods: The assay utilized a simple protein precipitation with sulfosalicylic acid followed by tert-butyl dimethylsilyl (TBDMS) derivatization of hydroxyl functional group by N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide (MTBSTFA). Results: Calibration curves of spiked pooled plasma showed a linear relationship in the range of 0.01 ng -2 mg with correlation coefficient value greater than 0.98. Limits of detection (LOD) and limits of quantification (LOQ) were found in the range of 0.9-8.8 ng and 9-88 ng, respectively. Conclusion: The new developed method might be useful for a rapid, sensitive screening of inherited fatty acid oxidation disorders. In addition, the method expected to be one of the alternative method for screening newborns of metabolic disorders in the laboratories where expensive MS/MS is unavailable.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.13 no.2
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• pp.75-80
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• 2013

Specific genetic conditions may lead to sudden unexpected deaths in infancy, such as inborn errors of fatty acid oxidation and genetic disorders of cardiac ion channels. The disease may present dramatically with severe hypoketotic hypoglycemia, Reye syndrome or sudden death, typically with a peak of frequency around 3-6 month, whilst neonatal sudden death is quite rare. When undetected, approximately 20-25% of infants will die or suffer permanent neurologic impairment as a consequence of the first acute metabolic decompensation. Meanwhile, the advent of newborn screening for metabolic diseases has revealed populations of patients with disorders of fatty acid oxidation (FAO), the most frequent of which is medium chain acyl-CoA dehydrogenase (MCAD) deficiency. Without this screening, affected individuals would likely succumb to sudden infant death syndrome (SIDS). Here we describe an overview of sudden infant death syndrome and inherited metabolic disorder.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.22 no.1
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• pp.1-8
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• 2022

Long-chain fatty acid oxidation disorders (LC-FAOD) are an autosomal recessive inherited rare disease group that result in an acute metabolic crisis and chronic energy deficiency owing to the deficiency in an enzyme that converts long-chain fatty acids into energy. LC-FAOD includes carnitine palmitoyltransferase type 1 (CPT1), carnitine-acylcarnitine translocase (CACT), carnitine palmitoyltransferase type 2 (CPT2), very long-chain acyl-CoA dehydrogenase (VLCAD), long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), and trifunctional protein (TFP) deficiencies. Common symptoms of LC-FAOD are hypoketotic hypoglycemia, cardiomyopathy, and myopathy. Depending on symptom onset, the disease can be divided as neonatal period, late infancy and early childhood, adolescence, or adult onset, but symptoms can appear at any time. The neonatal screening test (NBS) can be used to identify the characteristic plasma acylcarnitine profiles for each disease and confirmed by deficient enzyme analysis or molecular testing. Before introduction of NBS, the mortality rate of LC-FAOD was very high. With NBS implementation as routine neonatal care, the mortality rate was dramatically decreased, but severe symptoms such as rhabdomyolysis recur frequently and affect the quality of life. Triheptanoin (Dojolvi^®), the first drug for pediatric and adult patients with molecularly confirmed LC-FAOD, has recently been approved by the US Food and Drug Administration in 2020. In this review, the diagnosis of LC-FAOD and treatment including triheptanoin are summarized.

• Nutrition Research and Practice
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• v.7 no.4
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• pp.294-301
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• 2013

In this study, we examined the hepatic anti-steatosis activity of carnosic acid (CA), a phenolic compound of rosemary (Rosmarinus officinalis) leaves, as well as its possible mechanism of action, in a high-fat diet (HFD)-fed mice model. Mice were fed a HFD, or a HFD supplemented with 0.01% (w/w) CA or 0.02% (w/w) CA, for a period of 12 weeks, after which changes in body weight, blood lipid profiles, and fatty acid mechanism markers were evaluated. The 0.02% (w/w) CA diet resulted in a marked decline in steatosis grade, as well as in homeostasis model assessment of insulin resistance (HOMA-IR) index values, intraperitoneal glucose tolerance test (IGTT) results, body weight gain, liver weight, and blood lipid levels (P < 0.05). The expression level of hepatic lipogenic genes, such as sterol regulating element binding protein-1c (SREBP-1c), liver-fatty acid binding protein (L-FABP), stearoyl-CoA desaturase 1 (SCD1), and fatty acid synthase (FAS), was significantly lower in mice fed 0.01% (w/w) CA and 0.02% (w/w) CA diets than that in the HFD group; on the other hand, the expression level of ${\beta}$-oxidation-related genes, such as peroxisome proliferator-activated receptor ${\alpha}$ (PPAR-${\alpha}$), carnitine palmitoyltransferase 1 (CPT-1), and acyl-CoA oxidase (ACO), was higher in mice fed a 0.02% (w/w) CA diet, than that in the HFD group (P < 0.05). In addition, the hepatic content of palmitic acid (C16:0), palmitoleic acid (C16:1), and oleic acid (C18:1) was significantly lower in mice fed the 0.02% (w/w) CA diet than that in the HFD group (P < 0.05). These results suggest that orally administered CA suppressed HFD-induced hepatic steatosis and fatty liver-related metabolic disorders through decrease of de novo lipogenesis and fatty acid elongation and increase of fatty acid ${\beta}$-oxidation in mice.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.18 no.2
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• pp.35-42
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• 2018

Purpose: To follow up Korean patients with metabolic and endocrine disorders ascertained by Korea Genetics Research Center, and assess the long-term effectiveness of extended newborn screening program in Korea. Methods: From January 2000 to December 2017, tandem mass spectrometry and fluoroimmunoassay were employed in extended newborn screening (NBS). The NBS program obtained dried blood spots from 283,626 babies, 48 hours after birth, and screened for galactosemia, congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH), and 50 preventable inborn errors of amino acid, fatty acid, and organic acid metabolism. Results: 28 cases of amino acid disorders, 75 cases of organic acid disorders, 27 cases of fatty acid disorders, 51 cases of urea cycle disorders, 127 cases of CH, 14 cases of CAH, and 15 cases of galactosemia were ascertained through NBS and subsequent confirmatory laboratory tests. Patients with amino acid metabolic disorders, galactosemia, CH, or CAH were more likely to have a better long-term outcome if detected early. Early management of MSUD led to much better outcome in over 90%. Despite early intervention, 32% of other organic acidemia cases still resulted in developmental delay and neurological problems. Fatty acid disorders showed varied results; those with EMA and MCAD had a good outcome, but those with VLCAD had serious neurological problems and considerably higher mortality. 75% with UCD experienced serious neurological complications and higher mortality. Conclusion: The nation-wide NBS program must be accompanied by comprehensive long-term management and physician and family education of inborn errors of metabolism for a better outcome.

• Animal Bioscience
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• v.35 no.8
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• pp.1184-1194
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• 2022

Objective: High concentrate diets are widely used to satisfy high-yielding dairy cows; however, long-term feeding of high concentrate diets can cause subacute ruminal acidosis (SARA). The endocrine disturbance is one of the important reasons for metabolic disorders caused by SARA. However, there is no current report about thyroid hormones involved in liver metabolic disorders induced by a high concentrate diet. Methods: In this study, 12 mid-lactating dairy cows were randomly assigned to HC (high concentrate) group (60% concentrate of dry matter, n = 6) and LC (low concentrate) group (40% concentrate of dry matter, n = 6). All cows were slaughtered on the 21st day, and the samples of blood and liver were collected to analyze the blood biochemistry, histological changes, thyroid hormones, and the expression of genes and proteins. Results: Compared with LC group, HC group showed decreased serum triglyceride, free fatty acid, total cholesterol, low-density lipoprotein cholesterol, increased hepatic glycogen, and glucose. For glucose metabolism, the gene and protein expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase 1 in the liver were significantly up-regulated in HC group. For lipid metabolism, the expression of sterol regulatory element-binding protein 1, long-chain acyl-CoA synthetase 1, and fatty acid synthase in the liver was decreased in HC group, whereas carnitine palmitoyltransferase 1α and peroxisome proliferator activated receptor α were increased. Serum triiodothyronine, thyroxin, free triiodothyronine (FT3), and hepatic FT3 increased in HC group, accompanied by increased expression of thyroid hormone receptor (THR) in the liver. Conclusion: Taken together, thyroid hormones may increase hepatic gluconeogenesis, β-oxidation and reduce fatty acid synthesis through the THR pathway to participate in the metabolic disorders caused by a high concentrate diet.

• Microbiology and Biotechnology Letters
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• v.28 no.2
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• pp.124-127
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• 2000

Beneficial bacteria, which have been used for medical purpose and for medicines for treating intestinal disorders, include strains of Bifidobacterium sp., Lactobacillus sp., Enterococcus sp., Clostridium butyricum, Lactobacillus sporogenes, Bacillus subtilis, Bacillus polyfermenticus and the like. Bacillus polyfermenticuss SCD with is commonly called as Bispan strain has been appropriately used for the treatment of long-term intestinal disorders, since the live strains in the form of active endospores can successfully reach the target intestine. In this study, the identification and characterization of Bispan strain was done using SEM observation, API 50CHB kits, isoprenoid quinone analysis, and fatty acid analysis. These results suggest that Bispan strain is very similar to Bacillus subtilis.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.3 no.1
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• pp.86-93
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• 2003

Background : The SCL began screening of newborns and high risk group blood spots with tandem mass spectrometry (MS/MS) in April 2001. Our goal was to determine approximate prevalence of metabolic disorders, optimization of decision criteria for estimation of preventive effect with early diagnosis. This report describes the ongoing effort to identify more than 30 metabolic disorders by MS/MS in South Korea. Methods : Blood spot was collected from day 2 to 30 (mostly from day 2 to 10) after birth for newborn. Blood spot of high risk group was from the pediatric patients in NICU, developmental delay, mental retardation, strong family history of metabolic disorders. One punch (3.2 mm ID) of dried blood spots was extracted with $150{\mu}L$ of methanol containing isotopically labelled amino acids (AA) and acylcarnitines (AC) internal standards. Butanolic HCl was added and incubated at $65^{\circ}C$ for 15 min. The butylated extract was introduced into the inlet of MS/MS. Neutral loss of m/z 102 and parent ion mode of m/z 85 were set for the analyses of AA and AC, respectively. Diagnosis was confirmed by repeating acylcarnitine profile, urine organic acid and plasma amino acid analysis, direct enzyme assay, or molecular testing. Results : Approximately 31,000 neonates and children were screened and the estimated prevalence (newborn/high risk group), sensitivity, specificity and recall rate amounted to 1:2384/1:2066, 96.55%, 99.98%, and 0.73%, respectively. Confirmed 28 (0.09%) multiple metabolic disorders (newborn/high risk) were as follows; 13 amino acid disorders [classical PKU (3/4), BH4 deficient-hyperphenylalaninemia (0/1), Citrullinemia (1/0), Homocystinuria (0/2), Hypermethioninemia (0/1), Tyrosinemia (1/0)], 8 organic acidurias [Propionic aciduria (2/1), Methylmalonic aciduria (0/1), Isovaleric aciduria (1/1), 3-methylcrotonylglycineuria (1/0), Glutaric aciduria type1 (1/0)], 7 fatty acid oxidation disorders [LCHAD def. (2/2), Mitochondrial TFP def. (0/1), VLCAD def. (1/0), LC3KT def. (0/1). Conclnsion : The relatively normal development of 10 patients with metabolic disorders among newborns (except for the expired) demonstrates the usefulness of newborn screening by MS/MS for early diagnosis and medical intervention. However, close coordination between the MS/MS screening laboratory and the metabolic clinic/biochmical geneticists is needed to determine proper decision of screening parameters, confirmation diagnosis, follow-up scheme and additional tests.

• Korean Journal of Poultry Science
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• v.45 no.2
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• pp.109-118
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• 2018

A great progress in genetic selection, nutrition and management practices has contributed to the improved growth rate of broilers and egg production in laying hens. For the increased productivity of modern poultry, a healthy chicken liver needs to cope with the increased metabolic demands. The liver is the major site of de novo fatty acid synthesis; therefore, hepatic lipogenesis is crucial for producing better quality meat and eggs. When de novo lipogenesis exceeds the capacity of lipid metabolism and secretion, large amounts of lipids accumulate in the liver of broilers, leading to a fatty liver. Upon onset of egg-laying in hens, lipids including free fatty acids, triglycerides, and phospholipids are dramatically increased in blood plasma for the synthesis of yolk precursors in oocytes. Productive hens with fatty liver often have hemorrhagic syndrome and sudden death due to the heavy demands of yolk synthesis, which burdens the liver. Understanding the lipid metabolism and hepatic lipid disorders is a key point in the improvement of the growth and production of chickens. This review focuses on the recent studies on lipid metabolism, the hepatic lipid disorders, and the prevention or reduction of fatty liver in poultry.

• Molecules and Cells
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• v.37 no.8
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• pp.598-604
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• 2014

Fatty acids, important components of a normal diet, have been reported to play a role in bone metabolism. Osteoclasts are bone-resorbing cells that are responsible for many bone-destructive diseases such as osteoporosis. In this study, we investigated the impact of a medium-chain fatty acid, capric acid, on the osteoclast differentiation, function, and survival induced by receptor activator of NF-${\kappa}B$ ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Capric acid inhibited RANKL-mediated osteoclastogenesis in bone marrow-derived macrophages and suppressed RANKL-induced $I{\kappa}B{\alpha}$ phosphorylation, p65 nuclear translocation, and NF-${\kappa}B$ transcriptional activity. Capric acid further blocked the RANKL-stimulated activation of ERK without affecting JNK or p38. The induction of NFATc1 in response to RANKL was also attenuated by capric acid. In addition, capric acid abrogated M-CSF and RANKL-mediated cytoskeleton reorganization, which is crucial for the efficient bone resorption of osteoclasts. Capric acid also increased apoptosis in mature osteoclasts through the induction of Bim expression and the suppression of ERK activation by M-CSF. Together, our results reveal that capric acid has inhibitory effects on osteoclast development. We therefore suggest that capric acid may have potential therapeutic implications for the treatment of bone resorption-associated disorders.