• Journal of The Korean Society of Inherited Metabolic disease
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• 제22권1호
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• pp.21-27
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• 2022

Very long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency (VLCADD) leads to a defective 𝛽-oxidation, specifically during prolonged fasting, infection, or exercise. Patients with VLCADD usually suffer from cardiomyopathy, hypoketotic hypoglycemia, hepatic dysfunction, exercise intolerance, muscle pain, and rhabdomyolysis, and sometimes succumb to sudden death. VLCADD is generally classified into three phenotypes: severe early-onset cardiac and multiorgan failure, hypoketotic hypoglycemia, and later-onset episodic myopathy. Diagnostic evaluation comprises acylcarnitine analysis, genetic analysis, and VLCAD activity assay. In the acylcarnitine analysis, the key metabolites are C14:1, C14:2, C14, and C12:1. A C14:1 level >1 mmol/L strongly suggests VLCADD. Various treatment recommendations are available for this condition. Dietary management includes decreasing fat content, increasing medium-chain triglyceride levels, and decreasing fasting periods. Supplementation with L-carnitine is controversial. Triheptanoin (a seven-carbon fatty acid triglyceride) treatment demonstrates improvement of cardiac functions. Bezafibrate may improve the quality of life of patients with VLCAD.

• Journal of The Korean Society of Inherited Metabolic disease
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• 제19권1호
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• pp.20-25
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• 2019

Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (OMIM#201475) is an autosomal recessively inherited metabolic disorder of mitochondrial long-chain fatty acid oxidation. The clinical features of VLCAD deficiency is classified by three clinical forms according to the severity. Here, we report a case of later-onset episodic myopathic form of VLCAD deficiency whose diagnosis was confirmed by plasma acylcarnitine analysis and" multigene panel multigene panel sequencing. A 34-year old female patient visited genetics clinic for genetic evaluation for history of recurrent myopathy with intermittent rhabdomyolysis. She suffered first episode of rhabdomyolysis with acute renal failure requiring hemodialysis at twelve years old. After then, she suffered several times of recurrent rhabdomyolysis provoked by prolonged exercise or fasting. Physical and neurologic exam was normal. Serum AST/ALT and creatinine kinase (CK) levels were mildly elevated. However, according to her previous medical records, her AST/ALT, CK were highly elevated when she had rhabdomyolysis. In suspicion of fatty acid oxidation disorder, multigene panel sequencing and plasma acylcarnitine analysis were performed in non-fasting, asymptomatic condition for the differential diagnosis. Plasma acylcarnitine analysis revealed elevated levels of C14:1 ($1.453{\mu}mol/L$; reference, 0.044-0.285), and C14:2 ($0.323{\mu}mol/L$; 0.032-0.301) and upper normal level of C14 ($0.841{\mu}mol/L$; 0.065 -0.920). Two heterozygous mutation in ACADVL were detected by multigene panel sequencing and confirmed by Sanger sequencing: c.[1202G>A(;) 1349G>A] (p.[(Ser 401Asn)(;)(Arg450His)]). Diagnosis of VLCAD deficiency was confirmed and frequent meal with low-fat diet was educated for preventing acute metabolic derangement. Fatty acid oxidation disorders have diagnostic challenges due to their intermittent clinical and laboratorial presentations, especially in milder late-onset forms. We suggest that multigene panel sequencing could be a useful diagnostic tool for the genetically and clinically heterogeneous fatty acid oxidation disorders.

• Journal of The Korean Society of Inherited Metabolic disease
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• 제12권1호
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• pp.49-53
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• 2012

X-linked adrenoleukodystrophy (ALD) is a rare inherited metabolic disease which results in impaired peroxisomal ${\beta}$-oxidation and the accumulation of very long chain fatty acids (VLCFA) in the adrenal cortex, the myelin of the central nervous system, and the testes. X-linked ALD is caused by mutations in the ABCD1 gene encoding an ATP-binding cassette transporter superfamily located in the peroxisomal membrane. This disease is characterized by a variety of phenotypes. The classic childhood cerebral ALD is a rapidly progressive demyelinating condition affecting the cerebral white matter before the age of 10 years in boys. We report the case of a 8-year-old with childhood cerebral X-linked ALD who developed inattention, hyperactivity, motor incoordination and hemiparesis. We diagnosed ALD with elevated plasma very long chain fatty acid level and diffuse high signal intensity lesions in both parieto-occipital white matter and cerebellar white matter in brain MRI. We identified a novel c.983delT (p.Met329CysfsX7) mutation of the ABCD1 gene. There is no correlation between X-ALD phenotype and mutations in the ABCD1 gene. Further studies for searching additional non-genetic factor which determine the phenotypic variation will be needed.

• Asian-Australasian Journal of Animal Sciences
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• 제31권8호
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• pp.1127-1133
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• 2018

Objective: Genome wide association study was conducted to identify and validate candidate genes associated with fatty acid composition of pork. Methods: A total of 480 purebreed Duroc pigs were genotyped using IlluminaPorcine60k bead chips while the association test was implemented following genome-wide rapid association using Mixed Model and Regression-Genomic Control (GRAMMAR-GC) approach. Results: A total of 25, 29, and 16 single nucleotide polymorphisms (SNPs) were significantly associated with stearic (18:0), oleic (18:1) and saturated fatty acids (SFA), respectively. Genome wide significant variants were located on the same region of swine chromosome 14 (SSC14) that spanned from 120 to 124 Mb. Top SNP ALGA008191 was located at 5 kb near the stearoyl-CoA desaturase (SCD) gene. This gene is directly involved in desaturation of stearic acid into oleic acid. General relationship of significant SNPs showed high linkage disequilibrium thus genome-wide signals was attributed to SCD gene. However, understanding the role of other genes like elongation of very long chain fatty acids-3 (ELOVL3) located on this chromosomal segment might help in further understanding of metabolism and biosynthesis of fatty acids. Conclusion: Overall, this study provides evidence that validates SCD gene as strong candidate gene associated with fatty acid composition in Duroc pigs. Moreover, this study confirms significant SNPs near ELOVL3 gene.

• Journal of Applied Biological Chemistry
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• 제42권2호
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• pp.57-61
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• 1999

Seven numerically dominant 2-methyl-4-chlorophenoxyacetic acid (MCPA)-degrading bacteria were isolated from agricultural soils. The isolates utilized the herbicide MCPA as a sole carbon source, producing significant biomass in MCPA mineral medium. They exhibited diverse herbicide degradation capabilities, but most of them grew very slowly in mineral medium containing herbicide. The chromosomal DNA patterns of the isolates obtained by polymerase chain reaction amplification of repetitive extragenic palindromic sequences were distinct from each other. One isolate, SH3, which was identified as Sphingomonas species by fatty acid methyl ester analysis, was able to degrade 5 different phenoxyacetic acid herbicides within 4 days. This strain contains two plasmids, and the smaller one has a crucial role in herbicide degradation. MCPA treated into agricultural soils without indigenous MCPA-degraders persisted for a long time, but the application of the isolate SH3 resulted in rapid decline of MCPA concentration in the soil.

• Nutritional Sciences
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• 제4권1호
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• pp.3-12
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• 2001

Long chain polyunsaturated fatty acids (LCPUFA) are important components of brain phospholipds and play important role (s) in brain function. In rats, the maximum brain growth occurs during the period of lactation even though it happens during the third trimester of gestation in human. Since milk contained docosahexaenoic acid (DHA) even through the maternal diet had no DHA and/or a very small amount of its precursor, $\alpha$-linolenic acid ($\alpha$-LnA), an emphasis was given to maternal adipose tissue as a reservoir of this fatty acid. We, therefore, investigated the mesenteric and subcutaneous adipose tissues for their fatty acid composition in dams reared with different fat diets. Diets containing various amounts of $\omega$6 and $\omega$3 fatty acids were given to adult female rats (200-250g) throughout the pregnancy and lactation periods. Diets were composed of 10% (wt/wt) corn oil (CO), soybean oil (SO), perilla seed oil (PO) containing about 60% $\alpha$-LnA, or fish oil (FO) rich in eicosapentaenoic acid (EPA) and DHA. The fatty acid ompositions of mesenteric and subcutaneous fat were measured and evaluated at Day-2 and Day-15 after parturition. In general, major characteristics of dietary fatty acid composition was reflected on the fatty acid composition of adipose tissues. Dietary fatty acid composition was reflected more on mesenteric fat as compared to subcutaneous fat. Mesenteric fat was found to contain less arachidonic acid (AA) and mesenteric fats of CO, SO and PO groups contained less DHA than did the subcutaneous fat. The P/M/S ratios of adipose tissues were similar between experimental groups while dietary P/M/S ratios differed significantly. It was noticeable that a small proportion of DHA was found in the adipose tissues of animals of CO, SO and PO groups (Day-2) and in SO and PO groups (Day-15), the groups which do not contain DHA in their diets. The percentage of DHA in mesenteric fat o CO, SO and PO groups decreased as lactation continues, while the proportion of DHA in FO group increased. Adipose tissues of FO group had higher DHA/EPA ratio as compared to the diet. Considering the fact that the body contains a large amount of adipose tissues, our present finding suggests that the adipose tissue can serve as a reservoir of DHA for pregnant and lactating rats.

• Animal Bioscience
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• 제34권7호
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• pp.1210-1220
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• 2021

Objective: Unlike mammals, goose fatty liver shows a strong tolerance to fatty acids without obvious injury. Stearyl-coenzyme A desaturase 1 (SCD1) serves crucial role in desaturation of saturated fatty acids (SAFs), but its role in the SAFs tolerance of goose hepatocytes has not been reported. This study was conducted to explore the role of SCD1 in regulating palmitic acid (PA) tolerance of goose primary hepatocytes. Methods: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide was examined to reflect the effect of PA on hepatocytes viability, and quantitative polymerase chain reaction was used to detect the mRNA levels of several genes related to endoplasmic reticulum (ER) stress, inflammation, and apoptosis, and the role of SCD1 in PA tolerance of goose hepatocytes was explored using RNA interfere. Results: Our results indicated that goose hepatocytes exhibited a higher tolerant capacity to PA than human hepatic cell line (LO2 cells). In goose primary hepatocytes, the mRNA levels of fatty acid desaturation-related genes (SCD1 and fatty acid desaturase 2) and fatty acid elongate enzyme-related gene (elongase of very long chain fatty acids 6) were significantly upregulated with 0.6 mM PA treatment. However, in LO2 cells, expression of ER stress-related genes (x box-binding protein, binding immunoglobulin protein, and activating transcription factor 6), inflammatory response-related genes (interleukin-6 [IL-6], interleukin-1β [IL-1β], and interferon-γ) and apoptosis-related genes (bcl-2-associated X protein, b-cell lymphoma 2, Caspase-3, and Caspase-9) was significantly enhanced with 0.6 mM PA treatment. Additionally, small interfering RNA (siRNA) mediated downregulation of SCD1 significantly reduced the PA tolerance of goose primary hepatocytes under the treatment of 0.6 mM PA; meanwhile, the mRNA levels of inflammatory-related genes (IL-6 and IL-1β) and several key genes involved in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), forkhead box O1 (FoxO1), mammalian target of rapamycin and AMPK pathways (AKT1, AKT2, FoxO1, and sirtuin 1), as well as the protein expression of cytochrome C and the apoptosis rate were upregulated. Conclusion: In conclusion, our data suggested that SCD1 was involved in enhancing the PA tolerance of goose primary hepatocytes by regulating inflammation- and apoptosis-related genes expression.

• Animal Bioscience
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• 제36권1호
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• pp.132-143
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• 2023

Objective: The aim was to study the influence of cooling milk at 9℃ at the farm versus keeping it at 20℃ on Parmigiano Reggiano cheese lipolysis. Methods: A total of six cheesemaking trials (3 in winter and 3 in summer) were performed. In each trial, milk was divided continuously into two identical aliquots, one of which was kept at 9℃ (MC9) and the other at 20℃ (MC20). For each trial and milk temperature, vat milk (V-milk) and the resulting 21 month ripened cheese were analysed. Results: Fat and dry matter and fat/casein ratio were lower in MC9 V-milk (p≤0.05) than in MC20. Total bacteria, mesophilic lactic acid and psychrotrophic and lipolytic bacteria showed significant differences (p≤0.05) between the two V-milks. Regarding cheese, fat content resulted lower and crude protein higher (p≤0.05) both in outer (OZ) and in inner zone (IZ) of the MC9 cheese wheels. Concerning total fatty acids, the MC9 OZ had a lower concentration of butyric, capric (p≤0.05) and medium chain fatty acids (p≤0.05), while the MC9 IZ had lower content of butyric (p≤0.05), caproic (p≤0.01) and short chain fatty acids (p≤0.05). The levels of short chain and medium chain free fatty acids (p≤0.05) were lower and that of long chain fatty acids (p≤0.05) was higher in MC9 OZ cheese. The principal component analysis of total and free fatty acids resulted in a clear separation among samples by seasons, whereas slight differences were observed between the two different milk temperatures. Conclusion: Storing milk at 9℃ at the herd affects the chemical composition of Parmigiano Reggiano, with repercussion on lipolysis. However, the changes are not very relevant, and since the cheese can present a high variability among the different cheese factories, such changes should be considered within the "normal variations" of Parmigiano Reggiano chemical characteristics.

• Journal of The Korean Society of Inherited Metabolic disease
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• 제2권1호
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• pp.15-19
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• 2002

Disorders resulting from defects in peroxisomal biogenesis include Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease. The three diseases are now considered as a continuum of clinical features. Neonatal adrenoleukodystrophy is intermediate between Zellweger syndrome and infantile Refsum disease in severity, and is characterized by profound hypotonia, intractable seizures and premature death. We report a cases of neonatal adrenoleukodystrophy presenting with neonatal seizure and hypotonia. At the age of 43 months, she had clinical evidence of adrenal insufficiency with skin hyperpigmentation and electrolyte imbalance. She was diagnosed having neonatal adrenoleukodystrophy based on abnormally high levels of plasma very long-chain fatty acids, pipecolic acid and phytanic acid.

• Asian-Australasian Journal of Animal Sciences
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• 제33권12호
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• pp.1957-1964
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• 2020

Objective: The aim of this study was to compare overfeeding performance, fatty acid composition, blood chemistry, enzymes and genes expression overfed Xupu and Landes geese. Methods: Sixty male Xupu geese (80 d) and Landes geese (80 d) were selected. After a period of one-week of pre-overfeeding, Xupu and Landes geese were overfed three meals of 550 and 350 g/d, respectively, of a high-carbohydrate diet in the first week of the overfeeding period. The next week, geese were given four meals of 1,200 and 850 g/d, respectively, over 8 to 14 d. Finally, geese were given five meals of 1,600 and 1,350 g/d, respectively, for the last two weeks. Results: After overfeeding for 28 d: Compared with Landes geese, Xupu geese liver weight and liver-to-body weight ratio decreased (p<0.05), while final weight, slaughter weight, total weight gain, abdominal fat weight, and feed-to-liver weight ratio increased (p<0.05). The levels of elaidic acid (C18:1t9), oleic acid (C18:1n-9), eicosenoic acid, and arachidonic acid in the liver of Xupu geese significantly increased (p<0.05), and the levels of myristic acid and stearic acid significantly decreased (p<0.05), while methyleicosanoate acid significantly increased (p<0.05). Xupu geese had higher plasma concentrations of triglyceride and very low density lipoprotein cholesterol (p<0.05), and decreased activities of alanine aminotransferase, aspartate aminotransferase, and lipase (LPS) (p<0.05). Landes geese had higher LPS activity (p<0.05), but lower cholinesterase activity (p<0.05) when compared with Xupu geese. The mRNA expression levels of fatty acid dehydrogenase (FADS) gene, elongase of long-chain fatty acid 1 (ELOVL1) gene, ELOVL5, and acyl-Co A: cholesterol acyltransferase 2 (ACAT2) gene were significantly upregulated (p<0.05) in Landes goose when compared with Xupu geese. Conclusion: This study demonstrates that the liver production performance of Landes geese was better than that of Xupu geese to some extent, which may be closely related to LPS activity, as well as the expression of FADS, ELOVL1, ELOVL5, and ACAT2.