Genetic Determinants of Nutrient Processing
Emmanuel C. Opara, Sam Dagogo-Jack in Nutrition and Diabetes, 2019
Polyunsaturated fatty acid composition of phospholipids is associated with several common diseases, including the metabolic syndrome [50], CVD [51], psychiatric disorders [52,53], and immune-related disease [54]. Polyunsaturated fatty acid levels in phospholipids are determined by both nutrition and metabolism, with desaturases and elongases catalyzing their conversion. Human desaturases were first cloned and characterized in 1999, owing to their critical role in the availability of polyunsaturated fatty acids, which are important for a number of biological functions including brain development, inflammation, and hemostasis [55,56]. The fatty acid desaturase 1 gene (FADS1) encodes the Δ-5 desaturase, while the fatty acid desaturase 2 gene (FADS2) gene encodes the Δ-6 desaturase. Both the FADS1 and FADS2 genes are located on chromosome 11q12.2 in a head-to-head configuration. The Δ-5 desaturase is expressed at highest levels in the liver, with lower but comparable expression levels in the heart, brain, and lung, and low but detectable levels of expression in placenta, skeletal muscle, kidney, and pancreas. In comparison, the Δ-6 desaturase had a similar expression profile but with a greater overall abundance [55]. As depicted in Figure 2.2, these enzymes catalyze rate-limiting steps in the production of long chain fatty acids, including arachidonic acid (20:4(n-6)) and eicosapentaenoic acid (20:5(n-3)), which are precursors of eicosanoids, which mediate inflammatory processes [57,58].
Omega-3 Fatty Acids in the Prevention of Maternal and Offspring Metabolic Disorders
Nilanjana Maulik in Personalized Nutrition as Medical Therapy for High-Risk Diseases, 2020
An understanding of genetic variations has posed a big question on the appropriateness of the one-size-fits-all recommended dietary allowance. Recent studies on SNPs revealed that the differences from one person to another may be greater than previously thought. SNPs in the genes encoding the fatty acid desaturase and elongase enzymes affect longer chain PUFA production. As such, what is adequate for some may be deficient for others; it is therefore pertinent to consider individual genetic variations and move towards personalized nutrition, especially during pregnancy. Nutritional intervention has been suggested as a tool for improving virtually any condition. Information about person’s SNPs status would proffer a platform for designing a nutritional intervention strategy that can improve the maternal health status. For instance, DHA intake during pregnancy may prevent inflammation-inclined adverse pregnancy outcomes in mothers with low ALA to DHA conversion efficiency.
The Zone Diet
Caroline Apovian, Elizabeth Brouillard, Lorraine Young in Clinical Guide to Popular Diets, 2018
Sears helped to pioneer research proposing that the enzymes required for the synthesis of the eicosanoid precursors (DGLA, AA, and EPA) are common to both the ω-6 and ω-3 fatty acid metabolic pathways, which suggested the potential for manipulation of their enzymatic activity through dietary means. As both DGLA and EPA are substrates for the delta-5 desaturase enzyme, Sears posited that supplementation with EPA would act as a feedback inhibition, suppressing the delta-5 desaturase pathway, thereby reducing the production of AA from DGLA.9,16,17 Alterations in plasma AA:EPA ratio have been cited as causative of dysfunction in the metabolism of obese individuals, cautiously affirming the observation that fatty acid desaturase activity serves as a biomarker for the development of obesity and its related disorders.16,17
Changes in Serum, Red Blood Cell, and Colonic Fatty Acids in a Personalized Omega-3 Fatty Acid Supplementation Trial
Published in Nutrition and Cancer, 2022
Yifan Shen, Ananda Sen, D. Kim Turgeon, Jianwei Ren, Gillian Graifman, Mack T. Ruffin, William L. Smith, Dean E. Brenner, Zora Djuric
Fatty acids in serum, red blood cells, and colon were expressed as a mole percent of total fatty acids, and the ratio of EPA to AA was calculated using the mole percent values. This trial utilized doses of ω-3 fatty acid supplementation that were higher than in many other studies. We therefore calculated several published indices of ω-3 fatty acid status (Table 1). The Omega-3 index was calculated as the relative content of the sum of EPA and DHA in RBC membranes, expressed as a percent of total fatty acids by weight using the calculation method of Harris et al. (32). The ω-3 highly unsaturated fatty acids (HUFA) and ω-6 HUFA represent percentages of total HUFAs present as either ω-3 or ω-6, respectively; HUFAs are fatty acids with 20–22 carbons and more than three double bonds as described by Lands et al. (33). The HUFA quantified were 20:3 ω-6, 20:4 ω-6, 22-4 ω-6, 20:5 ω-3, 22:5 ω-3, and 22:6 ω-3. EPA percent was percentage of EPA in RBC total fatty acids, which has been suggested to serve as a biomarker of colon tumor EPA content by Watson et al. (34). Finally, we calculated fatty acid ratios that represent desaturase activities. These were the ratios of 18:1 to 18:0 and 16:1 to 16:0 to assess stearoyl CoA desaturase (SCD-1, δ-9 desaturase), and ratio of 20:4, ω-6 to 18:2, ω-6 to assess fatty acid desaturase activity (FADS, δ-5 desaturase).
Discovery of differentially expressed genes in the intestines of Pelteobagrus vachellii within a light/dark cycle
Published in Chronobiology International, 2020
Chuanjie Qin, Jiaxian Sun, Jun Wang, Yongwang Han, He Yang, Qingchao Shi, Yunyun Lv, Peng Hu
On the basis of the DEG annotation, more than 36 unigenes associated with the digestive system were noted, which showed significantly different expression in both groups (Table 3). Among them, 15 DEGs were related to amino acid metabolism, 2 DEGs were related to the biosynthesis of amino acids (including those encoding gastricsin, trypsin-3, chymotrypsin, pepsin A, excitatory amino acid transporter, and amino-acid oxidase). Nineteen DEGs were related to carbohydrate metabolism, including those encoding gastricsin, trypsin-3, chymotrypsin, pepsin A, excitatory amino acid transporter, and amino-acid oxidase (Table 3). Twenty-fur DEGs were related to lipid metabolism, and the biosynthesis of fatty acids, including those encoding adipose triglyceride lipase, lipoprotein lipase, phospholipase, fatty acid desaturase, fatty acid synthase, fatty acid-binding protein, and apolipoprotein (Table 3). Moreover, eight rhythm genes showed significantly different expression in both groups. For example, brain-muscle-Arnt-like 1, cryptochrome, circadian locomoter output cycles protein kaput, and period circadian protein homolog (Table 3).
EPA’s pleiotropic mechanisms of action: a narrative review
Published in Postgraduate Medicine, 2021
John R. Nelson, Matthew J. Budoff, Omar R. Wani, Viet Le, Dhiren K. Patel, Ashley Nelson, Richard L. Nemiroff
Omega-3 fatty acids may have a role in preventing severe outcomes of COVID-19 in certain populations. A case series of three patients with severe COVID-19 treated with icosapent ethyl gives some preliminary support to this contention [159]. In these patients, inflammatory markers decreased substantially after administration of icosapent ethyl and was associated with clinical improvement. Resolvins, protectins, and maresins derived from EPA and DHA have been shown to have antiviral activity in influenza, and have a role in resolution of inflammation [160]. However, resolvins have been shown to be reduced in patients with obesity, an important independent risk factor for morbidity and mortality due to SARS-CoV-2 infection [160]. As a result, it has been speculated that patients with obesity and a low level of pro-resolving mediators may be at higher risk for adverse outcomes. In addition, genetic variations in fatty acid desaturase and elongase genes, more frequent in African American and Hispanics, results in more efficient endogenous synthesis of arachidonic acid, shifting the EPA:arachidonic acid ratio toward a proinflammatory state and possibly greater susceptibility to COVID-19 [161]. Additional research is required to establish such a link between omega-3 fatty acid status and risk of severe COVID-19.
Related Knowledge Centers
- Carboxylic Acid
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- Polyunsaturated Fat
- Α-Linolenic Acid
- Gamma-Linolenic Acid
- Stearoyl-Coa 9-Desaturase