The Role of Omega 3 Fatty Acids in Regulating Gene Expression - Coursework Example

The Role of Omega 3 Fatty Acids in Regulating Gene Expression Inserts His/Her Inserts Grade Inserts s Name> 11, April, 2013 Contents Introduction 3 Expression system 3 Omega - fatty acids (n – 3 FA) and gene expression 4 The means by which Gene-Expression is Regulated by PUFA 6 Metabolic pathways of omega – 6 and omega – 3 7 Animal experiments 8 Role of rat hippocampus on gene expression 8 Role of Omega-3 fatty acid in regulating inflammatory cytokine 9 Conclusion 10 References 11 The Role of Omega 3 Fatty Acids in Regulating Gene Expression Introduction Gene expression is the process that leads to synthesis of a functional gene product by use of information from a gene. These products are mostly non-protein coding genes such as small nuclear RNA (snRNA) genes, transfer RNA (tRNA) and ribosomal RNA (rRNA) - their product is a functional RNA (Weiner, 2004). Gene expression is used by eukaryotes, probably induced by viruses in order to produce the macromolecular mechanism for life. A number of gene expression procedures can be modulated, including post-translational modification, RNA splicing, translation and transcription. Gene regulation has the capacity of giving the cell control over function and structure, which is the foundation of adaptability, versatility, morphogenesis, and cellular differentiation of any creature. In addition, gene regulation is charged with the function of acting as a substrate for evolutionary change, given that control of location, timing, and the quantity of gene expression can have significant impact on the roles of the gene in a multicellular creature or a cell itself (Brueckner , et al., 2009). Expression system An expression system is particularly designed for the production of a suitable gene product. This system is usually in form of a protein, but it is sometimes manifested in form of RNA such as ribozyme or tRNA. The system is also made of a gene, which is often encoded by DNA. As shown in Figure 1, there is also the molecular mechanism that is used in transcribing the DNA into mRNA and converts the mRNA into protein - this is achieved using the reagents that are available. Essentially, this system incorporates every living cell though, and a virus is a very good example where host cell is used the replication in the form of expression system (Amaral et al., 2008). Figure 1: Protein expression system Omega - fatty acids (n – 3 FA) and gene expression Fat has for a long time been known to be rich in calorie as well essential fatty acids. Due to their regulating property, fatty acids play important role in modifying the structure and functions of cell membrane (Prescott and Calder, 2004). Fatty acids are capable of regulating gene expression due to their successful downstream events and effects such as transformation of blood coagulation pathways and vascular resistance. Ideally, the most potent group of fatty acids in these paths is called omega-3 fatty acids or n – 3 (Clandinin et al., 1991). The n – 3 fatty acids are unique from the more common fatty acids because of their double bonds, their longer chain length, and the presence of 3 carbon atoms from the methyl terminal, which is the reason for its being referred as n – 3 (Seo, Blaner and Deckelbaum, 2005). As shown in figure 2, n – 3 fatty acids are regulators of many gene families. As shown, n – 3 influence the expression of quite a number of major proteins that play important role in lipid metabolism, inflammation, and energy consumption ( Deckelbaum, Worgall and Seo, 2006). As such, the effect of n – 3 includes promotion of lipid oxidation and reduction in inflammation, which improve energy consumption. However, regulation of expression of different proteins by n – 3 fatty acids can be done upwards or downwards (Lee and Hwang, 2002). Figure 2: a variety of gene families that are regulated by omega – 3 fatty acids (n – 3). Fatty acids with long chain are not soluble in water, but they are transmitted in plasma. They can either be arranged in complex structures of esterified in triacylglycerols as shown in Figure 2. Following absorptions and re-esterification in the chylomicrons or very low density lipoproteins, blood lipoproteins are manufactured from dietary lipids. Non-esterified form (NEFAs) is produced by plasma lipoproteins, which are hydrolyzed by lipoprotein lipase or by hepatic lipase. Subsequently, NEFAs are locally consumed by adipose tissue and muscles or by the liver. However, white adipose tissue (WAT) is involved in exclusive production of NEFAs, which happens during starvation as a result of lipolysis from the stored triacyglycerols. In white adipose tissue and liver, among other lipogenic tissues, fatty acids can also be manufactured from esterified and glucose (Duplus, Glorian, and Forest, 2000). Figure 2: Key pathways of fatty acids synthesis, transport and manufacture. Adipose tissue is the one that releases Fatty acids, by lipoproteins originating from the liver or from a lipid-rich meal or after lipolysis. While located across plasma membrane with the aid of fatty acids transporter (FAT) and loosely attached to albumin (ALB), fatty acids are circulated in the plasma (Berk and Cate, 2007). The means by which Gene-Expression is Regulated by PUFA A number of studies have shown that gene expression alteration can be straightforwardly achieved through definite transcriptional regulators and FABPs. There are four types of transcriptional factor whose profusion or activity is regulated by PUFA. These includes liver X receptors (LXRs) (α and β), PPARs (α, β, and γ), PPARs (α, β, and γ) and hepatic nuclear factor 4 α (HNF-4) (Ahmad, 2002). Both α and β LXRs have been proved to execute essential functions in brain, particularly performing homeostasis - neurodegenerative disorders can result if their fail to function properly (Kitajka et al., 2004). Metabolic pathways of omega – 6 and omega – 3 The metabolic pathways of omega – 6 and omega – 3 is as shown in figure 3. The most essential enzymes in this pathway include delta – 6 desaturases and delta – 5, which are predetermined by FADS2 and fatty acids desaturase (FADS1) in that order (Simopoulos, 2010). These enzymes use their dietary precursors ALA and LA to limit the rate of synthesis of arachidonic acid (AA), DHA, LC – PUFA and EPA. EPA and AA are the originating fatty acids, which are involved in synthesis of DHA for docosanoids and eicosanoids. Fig. 2: Metabolic pathways of omega – 6 and omega – 3 Animal experiments Role of rat hippocampus on gene expression An experiments carried out by Hajjar et al. (2012) studied the hippocampus of a rat in order to establish the impacts of dietary polyunsaturated fatty acids (PUFA) on gene expression of peroxisome – proliferator - activated receptors (PPARs). In this experiment, 30 male Sprague – Dawley rats were arbitrary assigned into 3 groups of 10 animals each, which were fed with food containing rations of 65:1, 22:1 or 4.5:1 of n – 3 and n – 6 PUFA. The spatial memory of the rats was then examined using the Morris Water Maze test, after 10 weeks. Real-time PCR was then used to determine the expression of PPARγ and PPARα. In their results, Hajjar et al. (2012) found that decreasing PUFA rations of n – 6: n – 3 diets improved the brain performance of the rats in the up regulation of PPARγ and PPARα gene expression along the Morris water maze test. The rats that had the lowest ratios of n – 6: n – 3 of PUFA exhibited the highest PPAR gene expression and spatial learning improvements. From this experiment, it can be concluded that if n – 6: n – 3 PUFA ratios is modulated in a certain diet, it may lead to increased hippocampal PPAR gene expression. This in turn enhances memory capacity and spatial learning of the rats (Hajjar et al., 2012). The anti-apoptotic and anti-inflammatory function of PPAR could play crucial roles in the enhancement of the mental capacity of the rat’s brain (Moreno, Farioli-Vecchioli and Ceru, 2004). The connections between adjustments between the learning process and PPARs expression can also be explained by their transcriptional function in long-term potentiation (LTP) and synaptic plasticity. The roles played by these transcription factors in manufacture of proteins are pertinent to the synaptic process, which play important role in the formation of long-term memory. Transcription is an important process that leads to long-term synaptic plasticity (Hiramatsu and Arimori, 1988). Role of Omega-3 fatty acid in regulating inflammatory cytokine Porphyromonas gingivalis is significantly involved in the etiology of adult periodontitis by stimulating inflammatory cytokines, which leads to alveolar bone resorption, periodontal tissue inflammation and gingival. This study, which was conducted by Kesavalu et al. (2007), was aimed at testing whether enriching a diet with omega – 3 fatty acid would put forth inflammatory impacts in the gingival tissue of rats infected with P. gingivalis. To test this, Kesavalu et al. (2007) fed rats with corn oil or fish oil as well as libitum for 22 weeks, which led to infection with P. gingivalis. After this procedures, the RNA in of the rats was examined for proinflammatory mediators, T helper type 1 and type 2 cytokines, tumor necrosis factor-alpha, antioxidant enzymes, 5-lipoxygenese and other related qualities (Selkoe, 2003). The results revealed that the rats that were fed with omega – 3 fatty acids experienced reduced proinflammatory cytokine gene expression and imporved IFN – gamma. Also improved was SOD and CAT messager RNA expression, which was an indication of a diet – induced modulation of host inflammatory response. Examination of alveolar bone resorption in the rats in comparison with gene expression character established negative rlatiohsips with SOD and CAT and a strong positive relationship with COX – 2, IL – 6, and IL – 1beta. These results imply that diets supplemented with omega – 3 fatty acids are involved in modulation of the host and local gingival inflammatory, as a result of infection with P. gingivalis, which has impacts on the alverolar bone resorption in rats (Kesavalu et al., 2007). Conclusion In reality, the role of transcription factor PPARs in the strengthening of memory capacity in the hippocampus of a rat enhances the performance of spatial memory. The PPARs plays specific roles in regulation of the expression of genes that perform neurotransmission, hence it is essential in performing difficult tasks such as memory formation and learning (Kameda et al., 2003). Their essential functions include regulation of genes encoding for neurotransmitter receptors among others. The effect of n – 3 PUFA on brain role is enhanced through stimulation of PPAR target gene expression such as fatty acid transport protein (FTTP), lipoprotein lipase (LPL), and acyl-CoA synthase (ACS) (Harris and von, 2004). References Ahmad, A., Murthy, M., Greiner, R. S., Moriguchi, T. and Salem, N., 2002. Nutr. Neurosci. 5, pp. 103–113. Amaral, P.P., Dinger, M.E., Mercer, T.R. and Mattick, J.S., 2008. The eukaryotic genome as an RNA machine. Science 319 (5871), pp. 1787–9 Berk, V. and Cate J.H., 2007. Insights into protein biosynthesis from structures of bacterial ribosomes. Curr. Opin. Struct. Biol. 17 (3), pp. 302–9. Brueckner, F. et al., 2009. 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