• 대한유전성대사질환학회지
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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.

• 대한유전성대사질환학회지
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• 제19권1호
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• pp.20-25
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• 2019

Very-long-chain acyl-CoA dehydrogenase (VLCAD) 결핍증은 상염색체 열성으로 유전되는 유전성대사질환으로 미토콘드리아에서 장쇄지방산의 산화 장애이다. VLCAD 결핍증의 임상증상은 중증도 및 발현 시기에 따라 심각한 심장 이상을 동반하는 신생아기 발현형, 소아기 발현형, 지발형의 세 가지로 분류할 수 있다. 저자들은 혈장 아실카르니틴 분석과 유전자패널 염기서열분석 방법으로 확진된 성인기 발현형 VLCAD 결핍증 1례를 경험하였기에 보고하고자 한다. 34세 여자가 반복되는 근육통증과 간헐적 횡문근융해증의 병력을 주소로 내원하였다. 환자는 12세에 처음으로 운동 후 횡문근융해증으로 급성 신부전이 발생하여 혈액 투석을 받고 회복하였다. 이후 환자는 장시간의 운동이나 금식 후에 반복적으로 근육통증과 횡문근융해증이 발생하였다. 내원 시 신체 검진과 신경학적 검진은 정상이었다. 내원시 혈장 AST/ALT, Creatinine kinase (CK)는 약간 상승해있었으나, 이전 의무기록에 의하면 횡문근융해증이 있을 당시 AST/ALT, CK는 매우 상승하였다. 환자의 병력을 토대로 지방산대사장애 의심하에 감별진단을 위하여, 유전자 패널 염기서열 분석과 혈장 아실카르니틴 분석을 시행하였다. 혈장 아실카르니틴 분석결과 C14:1 ($1.453{\mu}mol/L$; 참고치, 0.044-0.285)와 C14:2 ($0.323{\mu}mol/L$; 0.032-0.301)가 증가였고, C14 ($0.841{\mu}mol/L$; 0.065-0.920)는 높은 정상이었다. 유전자패널 염기서열분석에서는 ACADVL 유전자에서 두 개의 병원성변이가 이형접합으로 발견되었으며, 이는 Sanger 염기서열 분석으로 확진되었다: c.[1202G>A(;)1349G>A] (p.[(Ser401Asn)(;)(Arg 450His)]). 환자는 생화학적, 유전학적 검사결과를 바탕으로 지발형 VLCAD 결핍증으로 확진되어 저지방식이와 급성 대사장애를 예방하기 위한 영양 교육을 받았다. 경증의 지발형 지방산 대사장애는 임상증상과 생화학적 검사 이상이 간헐적으로 발생하기 때문에 진단이 어렵다. 유전자패널 염기서열 분석은 지방산대사 장애와 같이 임상증상과 원인 유전자 이상이 다양한 대사 이상질환에서 유용한 진단법이 될 수 있다.

• 대한유전성대사질환학회지
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• 제12권1호
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• pp.49-53
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• 2012

X 연관 부신백질이영양증(adrenoleukodystrophy, ALD)은 과산화소체베타산화과정(peroxisomal ${\beta}$-oxidation)의 장애로 매우긴사슬지방산(very long chain fatty acids, VLCFA)이 신경계의 백질과 부신피질 및 고환에 축척된다. 이 질환은 과산화소체막단백질(peroxisomal membrane protein)을 형성하는 Xq28에 위치하는 ATP-binding cassette, subfamily D, member 1 (ABCD1) 유전자 돌연변이에 의해 주로 발생한다. X 연관 ALD는 다양한 임상양상을 보이는데 전형적인 소아대뇌형 부신백질이영양증은 10세 이전의 남아에서 대뇌백질에 빠르게 진행하는 탈수초현상을 보인다. 8세 된 남자 환아로 정상발달과정을 보이던 중 초등학교 입학 후에 집중장애와 산만한 모습으로 인해 주의력결핍과다활동장애로 진단받고 치료를 받았었다. 환아는 내원 8개월 전부터 말이 어눌해 지고 걸을 때 오른 발을 끌며 자주 넘어지는 모습을 보여 내원하였고 오른쪽 상, 하지의 근력이 떨어지는 양상이 관찰되었다. 검사상 부신기능저하증 소견을 보였으며 혈청 지방산 분석검사에서는 C26:0, C42:0/C22:0, C26:0/C22:0가 증가하였다. 뇌 자기공명영상에서는 T2와 FLAIR 강조영상에서 양측의 두정후두부의 백질과 소뇌의 백질에서 대칭적으로 고신호강도를 보였다. 환아는 부신백질이영양증로 진단하였고 ABCD1 유전자 분석 검사에서 새로운 c.983delT (p.Met329CysfsX7) 돌연변이가 확인되었다. X 연관 ALD는 유전자형과 표현형에 연관성이 없으며 다양한 임상양상을 보이기 때문에 환자들마다 임상증상을 잘 관찰해야 하며 향후 유전자 기능을 좀 더 파악하고 임상증상에 영향을 주는 다른 요소에 대한 연구가 필요할 것이라 사료된다.

• 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.

• 대한유전성대사질환학회지
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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.