lipid synthesis

脂质合成
  • 文章类型: Journal Article
    近年来,微塑料(MPs)和纳米塑料(NPs)及其对人体健康影响的研究得到了广泛的关注。NPs对脂质代谢的影响和所涉及的具体机制仍然知之甚少。为了解决这个问题,我们利用高通量测序和分子生物学技术研究了在聚苯乙烯纳米塑料(PS-NP)存在下内质网(ER)应激如何影响肝脂质代谢.我们的研究结果表明,PS-NP激活PERK-ATF4信号通路,进而通过ATF4-PPARγ/SREBP-1途径上调与脂质合成相关的基因的表达。这种激活导致脂滴在肝脏中的异常积累。4-PBA,一种已知的ER应激抑制剂,被发现可减轻PS-NP诱导的脂质代谢紊乱。这些结果证明了PS-NP的肝毒性作用,并阐明了PS-NP诱导的异常脂质代谢的机制。
    In recent years, the study of microplastics (MPs) and nanoplastics (NPs) and their effects on human health has gained significant attention. The impacts of NPs on lipid metabolism and the specific mechanisms involved remain poorly understood. To address this, we utilized high-throughput sequencing and molecular biology techniques to investigate how endoplasmic reticulum (ER) stress might affect hepatic lipid metabolism in the presence of polystyrene nanoplastics (PS-NPs). Our findings suggest that PS-NPs activate the PERK-ATF4 signaling pathway, which in turn upregulates the expression of genes related to lipid synthesis via the ATF4-PPARγ/SREBP-1 pathway. This activation leads to an abnormal accumulation of lipid droplets in the liver. 4-PBA, a known ER stress inhibitor, was found to mitigate the PS-NPs-induced lipid metabolism disorder. These results demonstrate the hepatotoxic effects of PS-NPs and clarify the mechanisms of abnormal lipid metabolism induced by PS-NPs.
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  • 文章类型: Journal Article
    细胞因子信号传导抑制因子3(SOCS3)是调节乳畜乳合成的关键信号分子。然而,SOCS3调节羊奶中脂质合成的分子机制尚不清楚。本研究旨在使用RNA测序(RNA-seq)筛选山羊乳腺上皮细胞(GMEC)中与SOCS3调节的脂质合成相关的关键下游基因。将山羊SOCS3过表达载体(PC-SOCS3)和阴性对照(PCDNA3.1)转染到GMEC中。SOCS3过表达后细胞的总RNA用于RNA-seq,然后进行差异表达基因(DEG)分析,功能富集分析,和网络预测。SOCS3过表达显著抑制三酰甘油的合成,总胆固醇,非酯化脂肪酸,和积累的脂滴。总的来说,确定了430个DEG,包括226个下调基因和204个上调基因,SOCS3过表达后。功能注释显示DEGs主要与脂质代谢有关,细胞增殖,和凋亡。我们发现与脂质合成相关的基因,STAT2和FOXO6下调。此外,增殖相关基因BCL2,MMP11和MMP13上调,凋亡相关基因CD40下调。总之,在GMEC中过表达SOCS3后,六个DEGs被确定为乳脂合成的关键调节剂。我们的结果提供了新的候选基因和对山羊中SOCS3调节的乳脂合成的分子机制的见解。
    The suppressor of cytokine signaling 3 (SOCS3) is a key signaling molecule that regulates milk synthesis in dairy livestock. However, the molecular mechanism by which SOCS3 regulates lipid synthesis in goat milk remains unclear. This study aimed to screen for key downstream genes associated with lipid synthesis regulated by SOCS3 in goat mammary epithelial cells (GMECs) using RNA sequencing (RNA-seq). Goat SOCS3 overexpression vector (PC-SOCS3) and negative control (PCDNA3.1) were transfected into GMECs. Total RNA from cells after SOCS3 overexpression was used for RNA-seq, followed by differentially expressed gene (DEG) analysis, functional enrichment analysis, and network prediction. SOCS3 overexpression significantly inhibited the synthesis of triacylglycerol, total cholesterol, non-esterified fatty acids, and accumulated lipid droplets. In total, 430 DEGs were identified, including 226 downregulated and 204 upregulated genes, following SOCS3 overexpression. Functional annotation revealed that the DEGs were mainly associated with lipid metabolism, cell proliferation, and apoptosis. We found that the lipid synthesis-related genes, STAT2 and FOXO6, were downregulated. In addition, the proliferation-related genes BCL2, MMP11, and MMP13 were upregulated, and the apoptosis-related gene CD40 was downregulated. In conclusion, six DEGs were identified as key regulators of milk lipid synthesis following SOCS3 overexpression in GMECs. Our results provide new candidate genes and insights into the molecular mechanisms involved in milk lipid synthesis regulated by SOCS3 in goats.
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  • 文章类型: Journal Article
    不健康的生活方式(高脂肪饮食,吸烟,酒精消费,运动太少,等。)在当前社会中容易引起脂质代谢紊乱,影响机体的健康,诱发疾病的发生。皂甙,作为植物中存在的生物活性物质,有降脂作用,减少炎症,和抗动脉粥样硬化作用。皂苷被认为参与体内脂质代谢的调节;它抑制食欲,因此,通过调节下丘脑中的pro-opiomelanocortin/可卡因苯丙胺调节转录本(POMC/CART)神经元和神经肽Y/agouti相关肽(NPY/AGRP)神经元来减少能量摄入,食欲控制中心.皂苷直接激活AMP激活蛋白激酶(AMPK)信号通路和相关转录调节因子,如过氧化物酶体增殖物激活受体(PPAR),CCAAT/增强子结合蛋白(C/EBP),和固醇调节元件结合蛋白(SREBP)增加脂肪酸氧化并抑制脂质合成。它还通过调节肠道微生物及其代谢物和衍生物-短链脂肪酸(SCFA)来调节肠道-肝脏相互作用以改善脂质代谢,胆汁酸(BAs),三甲胺(TMA),脂多糖(LPS),etal.本文综述了不同皂苷对脂质代谢紊乱的积极作用,提示肠-肝轴在改善脂质代谢过程中起着至关重要的作用,可作为治疗靶点,为脂质代谢紊乱的治疗提供新策略。
    Unhealthy lifestyles (high-fat diet, smoking, alcohol consumption, too little exercise, etc.) in the current society are prone to cause lipid metabolism disorders affecting the health of the organism and inducing the occurrence of diseases. Saponins, as biologically active substances present in plants, have lipid-lowering, inflammation-reducing, and anti-atherosclerotic effects. Saponins are thought to be involved in the regulation of lipid metabolism in the body; it suppresses the appetite and, thus, reduces energy intake by modulating pro-opiomelanocortin/Cocaine amphetamine regulated transcript (POMC/CART) neurons and neuropeptide Y/agouti-related peptide (NPY/AGRP) neurons in the hypothalamus, the appetite control center. Saponins directly activate the AMP-activated protein kinase (AMPK) signaling pathway and related transcriptional regulators such as peroxisome-proliferator-activated-receptors (PPAR), CCAAT/enhancer-binding proteins (C/EBP), and sterol-regulatory element binding proteins (SREBP) increase fatty acid oxidation and inhibit lipid synthesis. It also modulates gut-liver interactions to improve lipid metabolism by regulating gut microbes and their metabolites and derivatives-short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine (TMA), lipopolysaccharide (LPS), et al. This paper reviews the positive effects of different saponins on lipid metabolism disorders, suggesting that the gut-liver axis plays a crucial role in improving lipid metabolism processes and may be used as a therapeutic target to provide new strategies for treating lipid metabolism disorders.
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  • 文章类型: Journal Article
    伪狂犬病病毒(PRV)被认为是导致Aujeszky病的双螺旋DNA病毒,这导致了全球相当大的经济影响。色氨酸-tRNA合成酶2(WARS2),参与蛋白质合成的线粒体蛋白质,其广泛的表达和在翻译过程中的重要作用是公认的。我们的研究结果表明,在细胞培养和动物模型中,PRV感染后WARS2的mRNA和蛋白质水平均增加。通过RNA干扰抑制PK-15细胞中的WARS2表达导致PRV感染率降低,而增强WARS2表达导致感染率增加。此外,发现响应PRV的WARS2激活依赖于cGAS/STING/TBK1/IRF3信号通路和干扰素-α受体-1,突出了其通过I型干扰素信号通路的调节.进一步的分析表明,降低WARS2水平阻碍了PRV促进蛋白质和脂质合成的能力。我们的研究提供了新的证据,表明WARS2通过其蛋白质和脂质水平的管理促进PRV感染,为开发针对PRV感染的预防和治疗措施提供了新的途径。
    The pseudorabies virus (PRV) is identified as a double-helical DNA virus responsible for causing Aujeszky\'s disease, which results in considerable economic impacts globally. The enzyme tryptophanyl-tRNA synthetase 2 (WARS2), a mitochondrial protein involved in protein synthesis, is recognized for its broad expression and vital role in the translation process. The findings of our study showed an increase in both mRNA and protein levels of WARS2 following PRV infection in both cell cultures and animal models. Suppressing WARS2 expression via RNA interference in PK-15 ​cells led to a reduction in PRV infection rates, whereas enhancing WARS2 expression resulted in increased infection rates. Furthermore, the activation of WARS2 in response to PRV was found to be reliant on the cGAS/STING/TBK1/IRF3 signaling pathway and the interferon-alpha receptor-1, highlighting its regulation via the type I interferon signaling pathway. Further analysis revealed that reducing WARS2 levels hindered PRV\'s ability to promote protein and lipid synthesis. Our research provides novel evidence that WARS2 facilitates PRV infection through its management of protein and lipid levels, presenting new avenues for developing preventative and therapeutic measures against PRV infections.
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  • 文章类型: Journal Article
    结论:EgMADS3,一个关键的转录因子,通过与EgLPAAT启动子结合正向调节MCFA的积累,提高油棕中果皮的脂质含量。脂质作为细胞膜的结构成分,作为细胞外部环境的渗透屏障。植物储存脂类中的中链脂肪酸是一种重要的可再生能源。植物脂质合成中MCFA生产的研究大多基于生化方法,转录调控在MCFA合成中的重要性及其在TAG中的掺入需要进一步研究。油棕是世界上产量最高的油料作物,在主要油料作物中产量最高。在这项研究中,表征了油棕中果皮中的MADS转录因子(EgMADS3)。通过VIGS病毒诱导的基因沉默,确定EgMADS3的潜在靶基因与中链脂肪酸(MCFA)的生物合成有关。原生质体瞬时转化和qRT-PCR分析表明EgMADS3正调控EgLPAAT的表达。酵母单杂交测定和EMSA的结果表明EgMADS3和EgLPAAT启动子之间的相互作用。通过遗传转化和脂肪酸分析,结论EgMADS3直接调控潜在靶基因EgLPAAT的中链脂肪酸合成途径,从而促进MCFA的积累并提高总脂质含量。本研究在油棕中链脂肪酸(MCFA)代谢中MADS家族转录因子的功能分析中具有创新性,为改善油棕中链状脂肪酸的代谢途径提供了一定的研究依据,并提高了植物中MCFA的合成。本研究结果将为进一步研究利用生物技术提高油棕油品质提供参考方向。
    CONCLUSIONS: EgMADS3, a pivotal transcription factor, positively regulates MCFA accumulation via binding to the EgLPAAT promoter, advancing lipid content in mesocarp of oil palm. Lipids function as the structural components of cell membranes, which serve as permeable barriers to the external environment of cells. The medium-chain fatty acid in the stored lipids of plants is an important renewable energy. Most research on MCFA production in plant lipid synthesis is based on biochemical methods, and the importance of transcriptional regulation in MCFA synthesis and its incorporation into TAGs needs further research. Oil palm is the most productive oil crop in the world and has the highest productivity among the main oil crops. In this study, the MADS transcription factor (EgMADS3) in the mesocarp of oil palm was characterized. Through the VIGS-virus induced gene silencing, it was determined that the potential target gene of EgMADS3 was related to the biosynthesis of medium-chain fatty acid (MCFA). Transient transformation in protoplasts and qRT-PCR analysis showed that EgMADS3 positively regulated the expression of EgLPAAT. The results of the yeast one-hybrid assays and EMSA indicated the interaction between EgMADS3 and EgLPAAT promoter. Through genetic transformation and fatty acid analysis, it is concluded that EgMADS3 directly regulates the mid-chain fatty acid synthesis pathway of the potential target gene EgLPAAT, thus promotes the accumulation of MCFA and improves the total lipid content. This study is innovative in the functional analysis of the MADS family transcription factor in the metabolism of medium-chain fatty acids (MCFA) of oil palm, provides a certain research basis for improving the metabolic pathway of chain fatty acids in oil palm, and improves the synthesis of MCFA in plants. Our results will provide a reference direction for further research on improving the oil quality through biotechnology of oil palm.
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  • 文章类型: Journal Article
    MORF4(染色体4上的死亡率因子)相关基因15(MRG15)是一种色域蛋白,存在于参与转录的各种多蛋白复合物中,DNA修复,和发展。在这里,我们总结了MRG15在调节肝脏代谢方面的最新进展,无论是通过它的染色质结合能力,还是独立于它,强调MRG15是肝脏代谢性疾病的潜在治疗靶点。
    MORF4 (mortality factor on chromosome 4)-related gene 15 (MRG15) is a chromodomain protein that exists in various multiprotein complexes involved in transcription, DNA repair, and development. Here we summarize the recent advances involving MRG15 in modulating liver metabolism, both through its chromatin-binding capability and independently of it, highlighting MRG15 as a potential therapeutic target for liver metabolic diseases.
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  • 文章类型: Journal Article
    在这项研究中,外部农业植物激素(混合植物激素)添加(1.0、5.0、10.0和20.0mgL-1)对生长性能的影响,脂质生产率,研究了在含盐废水中培养的蛋白核小球藻的沉降效率。在评估的不同浓度中,添加10.0mgL-1农业植物激素时,微藻的生物量(1.00gL-1)和脂质生产率(11.11mgL-1d-1)最高。此外,外源农业植物激素也改善了蛋白核芽孢杆菌的沉降性能,这有利于微藻资源的收获,沉降性能的改善与农业植物激素用量呈正相关。微藻细胞中植物激素促进胞外聚合物合成可以认为是其促进微藻沉降的原因。转录组分析表明,植物激素的添加上调了丝裂原活化蛋白激酶(MAPK)介导的植物激素信号通路和脂质合成相关基因的表达,从而提高了蛋白核梭菌的盐度耐受性和脂质生产。总的来说,农业植物激素提供了一种有效且廉价的策略,用于提高在盐水废水中培养的微藻的脂质生产率和沉降效率。
    In this study, the effect of external agricultural phytohormones (mixed phytohormones) addition (1.0, 5.0, 10.0, and 20.0 mg L-1) on the growth performance, lipid productivity, and sedimentation efficiency of Chlorella pyrenoidosa cultivated in saline wastewater was investigated. Among the different concentrations evaluated, the highest biomass (1.00 g L-1) and lipid productivity (11.11 mg L-1 d-1) of microalgae were obtained at 10.0 mg L-1 agricultural phytohormones addition. Moreover, exogenous agricultural phytohormones also improved the sedimentation performance of C. pyrenoidosa, which was conducive to the harvest of microalgae resources, and the improvement of sedimentation performance was positively correlated with the amount of agricultural phytohormones used. The promotion of extracellular polymeric substances synthesis by phytohormones in microalgal cells could be considered as the reason for its promotion of microalgal sedimentation. Transcriptome analysis revealed that the addition of phytohormones upregulated the expression of genes related to the mitogen-activated protein kinase (MAPK)-mediated phytohormone signaling pathway and lipid synthesis, thereby improving salinity tolerance and lipid production in C. pyrenoidosa. Overall, agricultural phytohormones provide an effective and inexpensive strategy for increasing the lipid productivity and sedimentation efficiency of microalgae cultured in saline wastewater.
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  • 文章类型: Journal Article
    肝细胞癌(HCC)是一种严重的恶性肿瘤,对整体健康有深远的影响。常伴有不良预后。尽管这种疾病的诊断和治疗取得了一些进展,改善HCC的预后仍然是一个巨大的挑战。值得注意的是,脂质代谢在发病中起着关键作用,发展,和肿瘤细胞的进展。现有研究表明靶向脂质代谢在HCC治疗中的潜在应用。这篇综述旨在深入探索肝癌中脂质代谢的变化。详细介绍了与针对脂质代谢的创新治疗策略相关的潜在优势。靶向脂质代谢有望潜在地增强HCC的预后。
    Hepatocellular carcinoma (HCC) stands as a severe malignant tumor with a profound impact on overall health, often accompanied by an unfavorable prognosis. Despite some advancements in the diagnosis and treatment of this disease, improving the prognosis of HCC remains a formidable challenge. It is noteworthy that lipid metabolism plays a pivotal role in the onset, development, and progression of tumor cells. Existing research indicates the potential application of targeting lipid metabolism in the treatment of HCC. This review aims to thoroughly explore the alterations in lipid metabolism in HCC, offering a detailed account of the potential advantages associated with innovative therapeutic strategies targeting lipid metabolism. Targeting lipid metabolism holds promise for potentially enhancing the prognosis of HCC.
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  • 文章类型: Journal Article
    背景:断奶通常会导致仔猪的低采食量和体重减轻,动员脂质以激发能量。微生物来源的抗氧化剂(MA)在抗氧化方面表现出巨大的潜力,抗炎和代谢调节。
    目的:研究断奶仔猪断奶后脂代谢的变化及MA对断奶仔猪生长性能和肝脏脂代谢的影响。
    方法:在第一个实验中,断奶21日龄的仔猪在断奶日(d0)宰杀,断奶后4(d4)和14(d14)天(每天6只仔猪)。在第二个实验中,仔猪分为两组,接受MA(MA)和盐水灌胃(CON),分别。所有仔猪在21日龄时断奶,每组6只仔猪在25日龄时屠宰。
    结果:在实验1中,血清TG,与d0相比,d4和d14的TC和LDL-C明显下降(P<0.05)。d0时血清瘦素高于d4和d14时(P<0.05)。血清ghrelin从d0到d14持续升高(P<0.05)。肝脏HSL和ATGL从d0到d4先升高,然后从d4到d14下降(P<0.05)。实验2中,与CON组相比,MA组21-25日龄的ADG和ADFI升高(P<0.05)。血清TC,与CON组相比,MA组肝组织TC和血糖明显升高(P<0.05)。MA组SCD1、ACAT2和PPARγ表达上调(P<0.05)。与p-AMPKα(Thr172)表达降低相反,核SREBP1c,MA组FASN、PPARγ较CON组升高(P<0.05)。
    结论:断奶促进肝脏脂解,MA可通过调节AMPKα-SREBP1c通路促进脂质合成,从而提高断奶仔猪的生长性能。
    Weaning usually causes low feed intake and weight loss in piglets, which mobilizes lipid to energize. The microbe-derived antioxidants (MAs) exhibit great potential in antioxidation, anti-inflammation, and metabolic regulation.
    We aimed to investigate the changes of lipid metabolism postweaning and effects of MA on growth performance and hepatic lipid metabolism in weanling piglets.
    In the first experiment, piglets weaned at 21 d of age were slaughtered on weaning day (d0), 4 (d4), and 14 (d14) postweaning (6 piglets per day). In the second experiment, piglets were divided into 2 groups, receiving MA (MA) and saline gavage (CON), respectively. All piglets were weaned at 21 d of age and 6 piglets from each group were slaughtered at 25 d of age.
    In experiment 1, the serum triglyceride, total cholesterol (TC), and LDL cholesterol on d4 and d14 declined significantly compared with d0 (P < 0.05). The serum leptin on d0 was higher than that on d4 and d14 (P < 0.05). The serum ghrelin kept increasing from d0 to d14 (P < 0.05). The hepatic hormone-sensitive lipase and adipose triglyceride lipase first increased from d0 to d4 and then decreased from d4 to d14 (P < 0.05). In experiment 2, the average daily gain and average daily feed intake from 21 to 25 d of age increased in the MA group compared with the CON group (P < 0.05). The serum TC, hepatic TC, and glucose of MA group showed a significant increase than that of the CON group (P < 0.05). The expression of SCD1, ACAT2, and PPARγ were upregulated in the MA group (P < 0.05). Contrary to the decreased expression of phosphorylation of adenosine 5\'-monophosphate-activated protein kinase alfa subunit (Thr172), the nuclear sterol regulatory element-binding protein 1c, fatty acid synthase, and peroxisome proliferator-activated receptor gamma of MA group increased than that of CON group (P < 0.05).
    Weaning promoted hepatic lipolysis and MA could enhance lipid synthesis by regulating adenosine 5\'-monophosphate-activated protein kinase alfa subunit-sterol regulatory element-binding protein 1c pathway, thus improving growth performance of weanling piglets.
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  • 文章类型: Journal Article
    油棕,热带木本油料作物,广泛用于食品中,化妆品,和药品由于其高的生产效率和经济价值。棕榈油富含游离脂肪酸,多酚,维生素E,和其他营养素,适当食用对人体健康有益。因此,研究不同发育阶段游离脂肪酸含量的动态变化,并假设调节基因对游离脂肪酸代谢的影响,对于提高棕榈油质量和加速产业增长至关重要。LC-MS/MS用于分析95天后肉中游离脂肪酸的组成和含量(MS1和MT1),125天(MS2和MT2),和185天(MS3和MT3)无核(MS)和Tenera(MT)油棕物种果实授粉。RNA-Seq用于分析调节游离脂肪酸合成和积累的基因的表达,使用KEGG(京都基因和基因组百科全书)富集分析方法将基因和代谢物的差异映射到KEGG途径图。代谢组学研究在MS和MT的发展过程中确定了17种类型的饱和脂肪酸和13种类型的不饱和游离脂肪酸。转录组学研究表明,在MS和MT之间设定的差异基因阈值中,获得了10,804个显着不同的表达基因。结果表明,FabB与三种主要游离脂肪酸(硬脂酸,肉豆蔻酸,和棕榈酸),并与MS和MT的肉中游离棕榈酸的含量呈负相关。ACSL和FATB与三种主要游离脂肪酸含量呈正相关,与游离肉豆蔻酸含量呈负相关。研究揭示了关键酶基因的表达,FabB和FabF,可以改善油棕果肉中游离肉豆蔻酸的合成,而FabF,ACSL,和FATB基因可以促进游离棕榈油酸的产生。这些基因还可能促进油棕果肉中游离硬脂酸和棕榈油酸的合成。然而,FabB基因可能抑制硬脂酸合成,而ACSL和FATB基因可能会阻碍肉豆蔻酸的产生。本研究为提高棕榈油品质提供了理论依据。
    Oil palm, a tropical woody oil crop, is widely used in food, cosmetics, and pharmaceuticals due to its high production efficiency and economic value. Palm oil is rich in free fatty acids, polyphenols, vitamin E, and other nutrients, which are beneficial for human health when consumed appropriately. Therefore, investigating the dynamic changes in free fatty acid content at different stages of development and hypothesizing the influence of regulatory genes on free fatty acid metabolism is crucial for improving palm oil quality and accelerating industry growth. LC-MS/MS is used to analyze the composition and content of free fatty acids in the flesh after 95 days (MS1 and MT1), 125 days (MS2 and MT2), and 185 days (MS3 and MT3) of Seedless (MS) and Tenera (MT) oil palm species fruit pollination. RNA-Seq was used to analyze the expression of genes regulating free fatty acid synthesis and accumulation, with differences in genes and metabolites mapped to the KEGG pathway map using the KEGG (Kyoto encyclopedia of genes and genomes) enrichment analysis method. A metabolomics study identified 17 types of saturated and 13 types of unsaturated free fatty acids during the development of MS and MT. Transcriptomic research revealed that 10,804 significantly different expression genes were acquired in the set differential gene threshold between MS and MT. The results showed that FabB was positively correlated with the contents of three main free fatty acids (stearic acid, myristate acid, and palmitic acid) and negatively correlated with the contents of free palmitic acid in the flesh of MS and MT. ACSL and FATB were positively correlated with the contents of three main free fatty acids and negatively correlated with free myristate acid. The study reveals that the expression of key enzyme genes, FabB and FabF, may improve the synthesis of free myristate in oil palm flesh, while FabF, ACSL, and FATB genes may facilitate the production of free palmitoleic acid. These genes may also promote the synthesis of free stearic acid and palmitoleic acid in oil palm flesh. However, the FabB gene may inhibit stearic acid synthesis, while ACSL and FATB genes may hinder myristate acid production. This study provides a theoretical basis for improving palm oil quality.
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