• 제목/요약/키워드: Fatty acid metabolism

검색결과 562건 처리시간 0.027초

Improved Production of Long-Chain Fatty Acid in Escherichia coli by an Engineering Elongation Cycle During Fatty Acid Synthesis (FAS) Through Genetic Manipulation

  • Jeon, Eunyoung;Lee, Sunhee;Lee, Seunghan;Han, Sung Ok;Yoon, Yeo Joon;Lee, Jinwon
    • Journal of Microbiology and Biotechnology
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    • 제22권7호
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    • pp.990-999
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    • 2012
  • The microbial biosynthesis of fatty acid of lipid metabolism, which can be used as precursors for the production of fuels of chemicals from renewable carbon sources, has attracted significant attention in recent years. The regulation of fatty acid biosynthesis pathways has been mainly studied in a model prokaryote, Escherichia coli. During the recent period, global regulation of fatty acid metabolic pathways has been demonstrated in another model prokaryote, Bacillus subtilis, as well as in Streptococcus pneumonia. The goal of this study was to increase the production of long-chain fatty acids by developing recombinant E. coli strains that were improved by an elongation cycle of fatty acid synthesis (FAS). The fabB, fabG, fabZ, and fabI genes, all homologous of E. coli, were induced to improve the enzymatic activities for the purpose of overexpressing components of the elongation cycle in the FAS pathway through metabolic engineering. The ${\beta}$-oxoacyl-ACP synthase enzyme catalyzed the addition of acyl-ACP to malonyl-ACP to generate ${\beta}$-oxoacyl-ACP. The enzyme encoded by the fabG gene converted ${\beta}$-oxoacyl-ACP to ${\beta}$-hydroxyacyl-ACP, the fabZ catalyzed the dehydration of ${\beta}$-3-hydroxyacyl-ACP to trans-2-acyl-ACP, and the fabI gene converted trans-2-acyl-ACP to acyl-ACP for long-chain fatty acids. In vivo productivity of total lipids and fatty acids was analyzed to confirm the changes and effects of the inserted genes in E. coli. As a result, lipid was increased 2.16-fold higher and hexadecanoic acid was produced 2.77-fold higher in E. coli JES1030, one of the developed recombinants through this study, than those from the wild-type E. coli.

Gene Expression Profiling of Liver and Mammary Tissues of Lactating Dairy Cows

  • Baik, M.;Etchebarne, B.E.;Bong, J.;VandeHaar, M.J.
    • Asian-Australasian Journal of Animal Sciences
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    • 제22권6호
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    • pp.871-884
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    • 2009
  • Gene expression profiling is a useful tool for identifying critical genes and pathways in metabolism. The objective of this study was to determine the major differences in the expression of genes associated with metabolism and metabolic regulation in liver and mammary tissues of lactating cows. We used the Michigan State University bovine metabolism (BMET) microarray; previously, we have designed a bovine metabolism-focused microarray containing known genes of metabolic interest using publicly available genomic internet database resources. This is a high-density array of 70mer oligonucleotides representing 2,349 bovine genes. The expression of 922 genes was different at p<0.05, and 398 genes (17%) were differentially expressed by two-fold or more with 222 higher in liver and 176 higher in mammary tissue. Gene ontology categories with a high percentage of genes more highly expressed in liver than mammary tissues included carbohydrate metabolism (glycolysis, glucoenogenesis, propanoate metabolism, butanoate metabolism, electron carrier and donor activity), lipid metabolism (fatty acid oxidation, chylomicron/lipid transport, bile acid metabolism, cholesterol metabolism, steroid metabolism, ketone body formation), and amino acid/nitrogen metabolism (amino acid biosynthetic process, amino acid catabolic process, urea cycle, and glutathione metabolic process). Categories with more genes highly expressed in mammary than liver tissue included amino acid and sugar transporters and MAPK, Wnt, and JAK-STAT signaling pathways. Real-time PCR analysis showed consistent results with those of microarray analysis for all 12 genes tested. In conclusion, microarray analyses clearly identified differential gene expression profiles between hepatic and mammary tissues that are consistent with the differences in metabolism of these two tissues. This study enables understanding of the molecular basis of metabolic adaptation of the liver and mammary gland during lactation in bovine species.

Effects of Dietary Fat Levels on Lipid Parameters and Eicosanoids Production of Rats under Fixed N-6/N-3 and P/S Fatty Acid Ratios

  • Lee, Joon-Ho;Ikuo Ikeda;Michihiro Sugano
    • Nutritional Sciences
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    • 제5권4호
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    • pp.184-189
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    • 2002
  • The effects of dietary Int levels on lipid metabolism under fixed P/S (1.3) and n-6/n-3 (5.1) fatty acid ratios were examined in rats using palm oil, soybean oil and perilla oil. These ratios correspond to the recommended composition of dietary fat for humans. The range of dietary fat levels was 5-20% by weight (11.8-39.3% of total energy). The levels of dietary fat did not influence the concentrations of serum and liver cholesterol, whereas the level of triglycerides was gradually elevated with increasing levels of dietary fat, especially in the liver. The fatty acid composition of tissue phosphatidylcholine seemed to vary with the different levels of fat. The ratio of linoleic acid to arachidonic acid was increased more significantly in the heart than in the liver. In adipose tissue total lipids, the percentages of saturated and monounsaturated fatty acids decreased, whereas the percentage of polyunsaturated fatty acid increased, with increasing dietary Int levels. In addition, though the level of aortic prostacyclin was not uniformly affected by increasing dietary fat levels, thromboxane A2 production by platelets tended to increase with higher levels of dietary fat, suggesting an increased risk of thrombosis in this situation. Thus, even though dietary fat may have desirable compositions of fatty acids, these excessive consumption can produce unfavorable metabolic responses.

Effects of Dietary Fatty Acids on Serum Lipids and Fatty Acid Composition of Serum Phospholipids in Men

  • Joo, Oh-Eun;Sook, Kwon-Jong;Kyung, Chang-Yu
    • Journal of Nutrition and Health
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    • 제30권4호
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    • pp.415-424
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    • 1997
  • Serum lipid levels and fatty acid composition of serum phospholipids(PL) were investigated in 24 healthy male subjects who consumed either corn oil(CO) rich In linoleic acid(LA), perilla oil(PO) rich in $\alpha$-linolenic acid($\alpha$-LNA), or canola oil acid(OA) as a major fat source fir 5 weeks. The PO and the CNO groups showed significant(P <0.05) increases in serum high density lipoprotein-cholesterol(HDL-C) levels and in ratios of HDL- C/total cholesterol(TC) compared with initial values measured at the beginning of the study. Significantly(p <0.05) increased concentrations of serum triglycerides(TG) ware observed after 5 weeks of the CO based diet compared with both its intial value and the concentration observed after 5 weeks with the PO-based diet. fatty acid composition of serum PL reflected changes in dietary fatty acid composition and metabolism. Compared with the initial levels, significandy increased contents of eicosapentaenoic acid(EPA) and docosahexaenoic acid(DHA) were observed in serum PL of the PO group and significantly increased contents of $\alpha$-LNA and EPA were observed in the CNO group. Arachidonic acid(AA) content of serum PL did not change in the CO group during the study period, although, the increase in LA was significant(P <0.05). Compared with the CO-based diet, both the PO and the CNO-based diets seem to have beneficial effects on atherosclerosis by influencing the serum lipid profile and fatty acid composition of serum PL.

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Dietary Fatty Acids and Blood Cholesterol

  • Hayes, K.C.;Khosla, Pramod;Pronczuk, Andrzej;Lindsey, Saralyn
    • Journal of Nutrition and Health
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    • 제24권4호
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    • pp.378-392
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    • 1991
  • A series of studies in monkeys and hamsters, and reevaluation of published human data, indicate that dietary saturated fatty acids exert a dissimilar metabolic impact on cholesterol metabolism. Myristic acid(14 : 0) appears to have a major cholesterol-raising effect by means of decreasing LDL receptor activity and by increasing the direct production of LDL (from sources other than VLDL-catabolism) Palmitic acid (16 : 0) appears neutral in most cases (plasma cholesterol<200mg/dl) or until the LDL receptor is down-regulated, as with high cholesterol intake or obesity. In such cases. the down-regulated LDL receptors coupled with an increased VLDL production (induced by 16 : 0 and 18 : 1) can divert VLDL remnants to LDL and expand the LDL pool. Furthermore. the cholesterolemic impact of any saturated fatty acid can be countered up to a saturable 'threshold' level by dietary linoleic acid (18 : 2) which up-regulates the LDL receptor. Once above this 'threshold' the major fatty acids (16 : 0, 18 : 0, 18 : 1, 18 : 2, 18 : 3) appear to exert an equal impact on the circulating cholesterol concentration.

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버터, 정어리유 및 홍화유를 혼합 급이한 흰쥐의 혈청 및 간장의 지방산 대사에 미치는 영향 (Effects of the Feeding Mixed Oils of the Butter, Sardine and Safflower Oils on Fatty Acid Metabolism of Serum and Liver in Rats)

  • 김한수;김성희;정승용
    • 한국식품영양과학회지
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    • 제21권6호
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    • pp.617-626
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    • 1992
  • n-3계 EPA와 DHA의 함유 비율이 높은 정어리유와 n-6계 linoleic acid의 함유비율이 높은 홍화유의 혼합급여가 고지질 식이 흰쥐의 혈청 및 간장의 지방산 대사에 미치는 영향을 구명하기 위해 Sprague Dawley계 숫 흰쥐에게 버터 식이를 대조군으로 하고 정어리유 및 홍화유의 혼합 비율을 달리한 유지를 급여하여 4주간 실험 사육한 후 혈청 및 간장의 지방산 조성을 분석 검토한 결과, 혈청 인지질, 중성지질 및 콜레스테롤 에스테르의 지방산 조성은 홍화유의 혼합 비율이 증가함에 따라 n-3계 지방산 및 EPA/AA 비율은 감소되는 반면, n-6계 지방산 및 AA/PUFA 비율은 증가되는 경향을 보였다. 간장 지질중 중성지질의 조성 지방산 중 DHA 함유 비율이 가장 높았고, 콜레스테롤 에스테르에서는 linoleic acid의 함유 비율이 높았다. 혈청 및 간장 지질의 지방산 조성은 시험유지의 지방산 조성에 영향을 받는 것으로 나타났다.

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Dietary carnosic acid suppresses hepatic steatosis formation via regulation of hepatic fatty acid metabolism in high-fat diet-fed mice

  • Park, Mi-Young;Mun, Seong Taek
    • Nutrition Research and Practice
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    • 제7권4호
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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.

Elevated thyroid hormones caused by high concentrate diets participate in hepatic metabolic disorders in dairy cows

  • Chen, Qu;Wu, Chen;Yao, Zhihao;Cai, Liuping;Ni, Yingdong;Mao, Shengyong
    • Animal Bioscience
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    • 제35권8호
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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.

CRISPR/Cas9-mediated knockout of the Vanin-1 gene in the Leghorn Male Hepatoma cell line and its effects on lipid metabolism

  • Lu Xu;Zhongliang Wang;Shihao Liu;Zhiheng Wei;Jianfeng Yu;Jun Li;Jie Li;Wen Yao;Zhiliang Gu
    • Animal Bioscience
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    • 제37권3호
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    • pp.437-450
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    • 2024
  • Objective: Vanin-1 (VNN1) is a pantetheinase that catalyses the hydrolysis of pantetheine to produce pantothenic acid and cysteamine. Our previous studies have shown that the VNN1 is specifically expressed in chicken liver which negatively regulated by microRNA-122. However, the functions of the VNN1 in lipid metabolism in chicken liver haven't been elucidated. Methods: First, we detected the VNN1 mRNA expression in 4-week chickens which were fasted 24 hours. Next, knocked out VNN1 via CRISPR/Cas9 system in the chicken Leghorn Male Hepatoma cell line. Detected the lipid deposition via oil red staining and analysis the content of triglycerides (TG), low-density lipoprotein-C (LDL-C), and high-density lipoprotein-C (HDL-C) after VNN1 knockout in Leghorn Male Hepatoma cell line. Then we captured various differentially expressed genes (DEGs) between VNN1-modified LMH cells and original LMH cells by RNA-seq. Results: Firstly, fasting-induced expression of VNN1. Meanwhile, we successfully used the CRISPR/Cas9 system to achieve targeted mutations of the VNN1 in the chicken LMH cell line. Moreover, the expression level of VNN1 mRNA in LMH-KO-VNN1 cells decreased compared with that in the wild-type LMH cells (p<0.0001). Compared with control, lipid deposition was decreased after knockout VNN1 via oil red staining, meanwhile, the contents of TG and LDL-C were significantly reduced, and the content of HDL-C was increased in LMH-KO-VNN1 cells. Transcriptome sequencing showed that there were 1,335 DEGs between LMH-KO-VNN1 cells and original LMH cells. Of these DEGs, 431 were upregulated, and 904 were downregulated. Gene ontology analyses of all DEGs showed that the lipid metabolism-related pathways, such as fatty acid biosynthesis and long-chain fatty acid biosynthesis, were enriched. KEGG pathway analyses showed that "lipid metabolism pathway", "energy metabolism", and "carbohydrate metabolism" were enriched. A total of 76 DEGs were involved in these pathways, of which 29 genes were upregulated (such as cytochrome P450 family 7 subfamily A member 1, ELOVL fatty acid elongase 2, and apolipoprotein A4) and 47 genes were downregulated (such as phosphoenolpyruvate carboxykinase 1) by VNN1 knockout in the LMH cells. Conclusion: These results suggest that VNN1 plays an important role in coordinating lipid metabolism in the chicken liver.

Renal replacement therapy in neonates with an inborn error of metabolism

  • Cho, Heeyeon
    • Clinical and Experimental Pediatrics
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    • 제62권2호
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    • pp.43-47
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    • 2019
  • Hyperammonemia can be caused by several genetic inborn errors of metabolism including urea cycle defects, organic acidemias, fatty acid oxidation defects, and certain disorders of amino acid metabolism. High levels of ammonia are extremely neurotoxic, leading to astrocyte swelling, brain edema, coma, severe disability, and even death. Thus, emergency treatment for hyperammonemia must be initiated before a precise diagnosis is established. In neonates with hyperammonemia caused by an inborn error of metabolism, a few studies have suggested that peritoneal dialysis, intermittent hemodialysis, and continuous renal replacement therapy (RRT) are effective modalities for decreasing the plasma level of ammonia. In this review, we discuss the current literature related to the use of RRT for treating neonates with hyperammonemia caused by an inborn error of metabolism, including optimal prescriptions, prognosis, and outcomes. We also review the literature on new technologies and instrumentation for RRT in neonates.