• Title/Summary/Keyword: ELOVL

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Rapamycin Inhibits Expression of Elongation of Very-long-chain Fatty Acids 1 and Synthesis of Docosahexaenoic Acid in Bovine Mammary Epithelial Cells

  • Guo, Zhixin;Wang, Yanfeng;Feng, Xue;Bao, Chaogetu;He, Qiburi;Bao, Lili;Hao, Huifang;Wang, Zhigang
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.11
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    • pp.1646-1652
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    • 2016
  • Mammalian target of rapamycin complex 1 (mTORC1) is a central regulator of cell growth and metabolism and is sufficient to induce specific metabolic processes, including de novo lipid biosynthesis. Elongation of very-long-chain fatty acids 1 (ELOVL1) is a ubiquitously expressed gene and the product of which was thought to be associated with elongation of carbon (C) chain in fatty acids. In the present study, we examined the effects of rapamycin, a specific inhibitor of mTORC1, on ELOVL1 expression and docosahexaenoic acid (DHA, C22:6 n-3) synthesis in bovine mammary epithelial cells (BMECs). We found that rapamycin decreased the relative abundance of ELOVL1 mRNA, ELOVL1 expression and the level of DHA in a time-dependent manner. These data indicate that ELOVL1 expression and DHA synthesis are regulated by mTORC1 in BMECs.

Apolipoprotein H: a novel regulator of fat accumulation in duck myoblasts

  • Ziyi, Pan;Guoqing, Du;Guoyu, Li;Dongsheng, Wu;Xingyong, Chen;Zhaoyu, Geng
    • Journal of Animal Science and Technology
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    • v.64 no.6
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    • pp.1199-1214
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    • 2022
  • Apolipoprotein H (APOH) primarily engages in fat metabolism and inflammatory disease response. This study aimed to investigate the effects of APOH on fat synthesis in duck myoblasts (CS2s) by APOH overexpression and knockdown. CS2s overexpressing APOH showed enhanced triglyceride (TG) and cholesterol (CHOL) contents and elevated the mRNA and protein expression of AKT serine/threonine kinase 1 (AKT1), ELOVL fatty acid elongase 6 (ELOVL6), and acetyl-CoA carboxylase 1 (ACC1) while reducing the expression of protein kinase AMP-activated catalytic subunit alpha 1 (AMPK), peroxisome proliferator activated receptor gamma (PPARG), acyl-CoA synthetase long chain family member 1 (ACSL1), and lipoprotein lipase (LPL). The results showed that knockdown of APOH in CS2s reduced the content of TG and CHOL, reduced the expression of ACC1, ELOVL6, and AKT1, and increased the gene and protein expression of PPARG, LPL, ACSL1, and AMPK. Our results showed that APOH affected lipid deposition in myoblasts by inhibiting fatty acid beta-oxidation and promoting fatty acid biosynthesis by regulating the expression of the AKT/AMPK pathway. This study provides the necessary basic information for the role of APOH in fat accumulation in duck myoblasts for the first time and enables researchers to study the genes related to fat deposition in meat ducks in a new direction.

Comparison of overfed Xupu and Landes geese in performance, fatty acid composition, enzymes and gene expression related to lipid metabolism

  • Liu, Xu;Li, Peng;He, Changqing;Qu, Xiangyong;Guo, Songchang
    • Asian-Australasian Journal of Animal Sciences
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    • v.33 no.12
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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.

Sexual Maturation May Affect the Levels of n-6 PUFA in Muscle Tissues of Male Mice

  • Park, Chang Seok;Choi, Inho;Park, Young Sik
    • Journal of Animal Science and Technology
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    • v.55 no.2
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    • pp.147-153
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    • 2013
  • Lipid metabolism in mature male mice may be different from immature male mice, but the relationship of lipid metabolism, especially n-6 fatty acid metabolism, and sexual maturation is not clearly established. This study was carried out to elucidate whether sexual maturation may affect the metabolism of functional n-6 fatty acids of lipid components by investigating the composition of fatty acids in the longissimus muscle tissues of mature and immature male mice with GC and analyzing the expression of genes and proteins for synthesis of n-6 fatty acids with real-time PCR and western blotting, respectively. Mature male mice showed significantly higher testosterone level in the sera. Similarly, n-6 fatty acids, levels of linoleic acid (LA 18:2n-6) and total n-6 PUFA (Polyunsaturated fatty acids) were increased, but the levels of ${\gamma}$-linolenic acid (GLA; 18:3n-6), dihomo-${\gamma}$-linolenic acid (DGLA; 20:3n-6) and arachidonic acid (AA; 20:4 n-6) were decreased in the mature male mice. mRNA levels of ${\Delta}5$-desaturase (FASD1) and elongase (ELOVL5) genes related to n-6 fatty acid metabolism increased. However, the level of FADS1 protein only increased in mature male mice. In conclusion, this study suggested that sexual maturation of male mice affected n-6 fatty acid metabolism by stimulating the expression of enzyme FADS1 of n-6 PUFA metabolism.

Genome wide association study of fatty acid composition in Duroc swine

  • Viterbo, Vanessa S.;Lopez, Bryan Irvine M.;Kang, Hyunsung;Kim, Hoonseop;Song, Choul-won;Seo, Kang Seok
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.8
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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.

Epistatic Effects of Six Candidate Genes on Fatty Acid Composition in Korean Native Chicken

  • Jin, Shil;Lee, Seung Hwan;Lee, Doo Ho;Lee, Jun Heon
    • Korean Journal of Poultry Science
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    • v.48 no.2
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    • pp.51-58
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    • 2021
  • Fatty acid composition is an important economic trait that affects meat flavor. Several genes that influence fatty acid composition in meat have been investigated. In a previous study, we identified 51 significant SNP × SNP interactions (P≤0.05) between nine SNPs of six candidate genes (DEGS1, ELOVL6, FABP3, FABP4, FASN, and SCD) on meat fatty acid composition in Korean native chicken. This study further investigated the patterns of the SNP × SNP interactions to understand how they affect the fatty acid content in thigh and breast meat of Korean native chicken. The significant epistatic effects of SNP combinations showed various patterns for each fatty acid trait. The results of this study suggest that the respective additive effects of each SNP on polygenic traits, such as fatty acid composition, should be considered in combination with the epistatic effect of SNP combinations in animal breeding programs. The findings of this study have provided new genetic information for improving meat quality, especially the fatty acid composition, of Korean native chicken.

Metabolism of Very Long-Chain Fatty Acids: Genes and Pathophysiology

  • Sassa, Takayuki;Kihara, Akio
    • Biomolecules & Therapeutics
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    • v.22 no.2
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    • pp.83-92
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    • 2014
  • Fatty acids (FAs) are highly diverse in terms of carbon (C) chain-length and number of double bonds. FAs with C>20 are called very long-chain fatty acids (VLCFAs). VLCFAs are found not only as constituents of cellular lipids such as sphingolipids and glycerophospholipids but also as precursors of lipid mediators. Our understanding on the function of VLCFAs is growing in parallel with the identification of enzymes involved in VLCFA synthesis or degradation. A variety of inherited diseases, such as ichthyosis, macular degeneration, myopathy, mental retardation, and demyelination, are caused by mutations in the genes encoding VLCFA metabolizing enzymes. In this review, we describe mammalian VLCFAs by highlighting their tissue distribution and metabolic pathways, and we discuss responsible genes and enzymes with reference to their roles in pathophysiology.

Molecular Prognostic Profile of Egyptian HCC Cases Infected with Hepatitis C Virus

  • Zekri, Abdel-Rahman N.;Hassan, Zeinab K.;Bahnassy, Abeer A.;Sherif, Ghada M.;ELdahshan, Dina;Abouelhoda, Mohamed;Ali, Ahmed;Hafez, Mohamed M.
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5433-5438
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    • 2012
  • Background: Hepatocellular carcinoma (HCC) is a common and aggressive malignancy. Despite of the improvements in its treatment, HCC prognosis remains poor due to its recurrence after resection. This study provides complete genetic profile for Egyptian HCC. Genome-wide analyses were performed to identify the predictive signatures. Patients and Methods: Liver tissue was collected from 31 patients with diagnosis of HCC and gene expression levels in the tumours and their adjacent non-neoplastic tissues samples were studied by analyzing changes by microarray then correlate these with the clinico-pathological parameters. Genes were validated in an independent set by qPCR. The genomic profile was associated with genetic disorders and cancer focused on gene expression, cell cycle and cell death. Molecular profile analysis revealed cell cycle progression and arrest at G2/M, but progression to mitosis; unregulated DNA damage check-points, and apoptosis. Result: Nine hundred fifty eight transcripts out of the 25,000 studied cDNAs were differentially expressed; 503 were up-regulated and 455 were down-regulated. A total of 19 pathways were up-regulated through 27 genes and 13 pathways were down-regulated through 19 genes. Thirty-seven genes showed significant differences in their expression between HCC cases with high and low Alpha Feto Protein ($AFP{\geq}600$ IU/ml). The validation for the microarray was done by real time PCR assay in which PPP3CA, ATG-5, BACE genes showed down-regulation and ABCG2, RXRA, ELOVL2, CXR3 genes showed up-regulation. cDNA microarrays showed that among the major upregulated genes in HCC are sets. Conclusion: The identified genes could provide a panel of new diagnostic and prognostic aids for HCC.

t10,c12 Conjugated Linoleic Acid Upregulates Hepatic De Novo Lipogenesis and Triglyceride Synthesis via mTOR Pathway Activation

  • Go, Gwang-Woong;Oh, Sangnam;Park, Miri;Gang, Gyoungok;McLean, Danielle;Yang, Han-Sul;Song, Min-Ho;Kim, Younghoon
    • Journal of Microbiology and Biotechnology
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    • v.23 no.11
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    • pp.1569-1576
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    • 2013
  • In mice, supplementation of t10,c12 conjugated linoleic acid (CLA) increases liver mass and hepatic steatosis via increasing uptake of fatty acids released from adipose tissues. However, the effects of t10,c12 CLA on hepatic lipid synthesis and the associated mechanisms are largely unknown. Thus, we tested the hypothesis that gut microbiota-producing t10,c12 CLA would induce de novo lipogenesis and triglyceride (TG) synthesis in HepG2 cells, promoting lipid accumulation. It was found that treatment with t10,c12 CLA ($100{\mu}M$) for 72 h increased neutral lipid accumulation via enhanced incorporation of acetate, palmitate, oleate, and 2-deoxyglucose into TG. Furthermore, treatment with t10,c12 CLA led to increased mRNA expression and protein levels of lipogenic genes including SREBP1, ACC1, FASN, ELOVL6, GPAT1, and DGAT1, presenting potential mechanisms by which CLA may increase lipid deposition. Most strikingly, t10,c12 CLA treatment for 3 h increased phosphorylation of mTOR, S6K, and S6. Taken together, gut microbiota-producing t10,c12 CLA activates hepatic de novo lipogenesis and TG synthesis through activation of the mTOR/SREBP1 pathway, with consequent lipid accumulation in HepG2 cells.

Deficiency or activation of peroxisome proliferator-activated receptor α reduces the tissue concentrations of endogenously synthesized docosahexaenoic acid in C57BL/6J mice

  • Hsiao, Wen-Ting;Su, Hui-Min;Su, Kuan-Pin;Chen, Szu-Han;Wu, Hai-Ping;You, Yi-Ling;Fu, Ru-Huei;Chao, Pei-Min
    • Nutrition Research and Practice
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    • v.13 no.4
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    • pp.286-294
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    • 2019
  • BACKGROUND/OBJECTIVES: Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LCPUFA), is acquired by dietary intake or the in vivo conversion of ${\alpha}$-linolenic acid. Many enzymes participating in LCPUFA synthesis are regulated by peroxisome proliferator-activated receptor alpha ($PPAR{\alpha}$). Therefore, it was hypothesized that the tissue accretion of endogenously synthesized DHA could be modified by $PPAR{\alpha}$. MATERIALS/METHODS: The tissue DHA concentrations and mRNA levels of genes participating in DHA biosynthesis were compared among $PPAR{\alpha}$ homozygous (KO), heterozygous (HZ), and wild type (WT) mice (Exp I), and between WT mice treated with clofibrate ($PPAR{\alpha}$ agonist) or those not treated (Exp II). In ExpII, the expression levels of the proteins associated with DHA function in the brain cortex and retina were also measured. An n3-PUFA depleted/replenished regimen was applied to mitigate the confounding effects of maternal DHA. RESULTS: $PPAR{\alpha}$ ablation reduced the hepatic Acox, Fads1, and Fads2 mRNA levels, as well as the DHA concentration in the liver, but not in the brain cortex. In contrast, $PPAR{\alpha}$ activation increased hepatic Acox, Fads1, Fads2, and Elovl5 mRNA levels, but reduced the DHA concentrations in the liver, retina, and phospholipid of brain cortex, and decreased mRNA and protein levels of the brain-derived neurotrophic factor in brain cortex. CONCLUSIONS: LCPUFA enzyme expression was altered by $PPAR{\alpha}$. Either $PPAR{\alpha}$ deficiency or activation-decreased tissue DHA concentration is a stimulus for further studies to determine the functional significance.