Importance of Dietary γ-Linolenic Acid in Human Health and Nutrition

Yang, Fan; Chapkin, Robert S.

doi:10.1093/jn/128.9.1411

Cited by 321 publications

(255 citation statements)

References 32 publications

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“…Despite the accumulation of 18:2n6, only a very small amount of 20:2n6 is produced, demonstrating that C18 fatty acids with a ⌬6 double bond are the preferred substrate for elongation. In humans, the ⌬6 desaturation step is thought to be the rate-limiting step in the conversion of the essential fatty acids to long-chain PUFAs, and reduced ⌬6 desaturase activity has been associated with diabetes, aging, atopic dermatitis, premenstrual syndrome, and rheumatoid arthritis (39).…”

Section: Discussionmentioning

confidence: 99%

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Genetic dissection of polyunsaturated fatty acid synthesis in Caenorhabditis elegans

Watts

Browse

2002

Proc. Natl. Acad. Sci. U.S.A.

358

411

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Polyunsaturated fatty acids (PUFAs) are important membrane components and precursors of signaling molecules. To investigate the roles of these fatty acids in growth, development, and neurological function in an animal system, we isolated Caenorhabditis elegans mutants deficient in PUFA synthesis by direct analysis of fatty acid composition. C. elegans possesses all the desaturase and elongase activities to synthesize arachidonic acid and eicosapentaenoic acid from saturated fatty acid precursors. In our screen we identified mutants with defects in each fatty acid desaturation and elongation step of the PUFA biosynthetic pathway. The fatty acid compositions of the mutants reveal the substrate preferences of the desaturase and elongase enzymes and clearly demarcate the steps of this pathway. The mutants show that C. elegans does not require n3 or ⌬5-unsaturated PUFAs for normal development under laboratory conditions. However, mutants with more severe PUFA deficiencies display growth and neurological defects. The mutants provide tools for investigating the roles of PUFAs in membrane biology and cell function in this animal model. P olyunsaturated fatty acid (PUFA) components of phospholipids are necessary to create a fluid membrane environment. In mammals, specific PUFA composition affects many cellular processes including modulation of ion channels (1, 2), endocytosis͞exocytosis (3), and activities of membrane-associated enzymes that are sensitive to the biophysical properties of lipid membranes (4). In addition, certain classes of PUFAs are precursors of powerful eicosanoid effectors such as prostaglandins and leukotrienes (5). Disruptions in proper PUFA intake and metabolism are associated with certain human disease states such as coronary artery disease, hypertension, diabetes, inflammatory disorders, and cancer (6). In most cases the mechanisms through which fatty acid composition affects these conditions are not well understood.Mammals require the essential fatty acids linoleic acid (18:2n6) and linolenic acid (18:3n3) in their diet. Desaturation and elongation of these fatty acids produce the C20 PUFAs that become membrane components and precursors for eicosanoids. Plants produce these essential n6 and n3 PUFAs by desaturating oleic acid (18:1n9) at C12 and C15 positions to produce 18:2n6 and 18:3n3 but rarely possess the enzymes necessary to desaturate and elongate them further into C20 PUFAs. The free-living nematode Caenorhabditis elegans synthesizes a wide range of PUFAs including arachidonic acid (20:4n6) and eicosapentaenoic acid (20:5n3) by using saturated fatty acids obtained from their Escherichia coli diet (7). To this end, C. elegans expresses the full range of desaturase activities found in plants (⌬12 and n3 desaturase) and animals (⌬5 and ⌬6 desaturase) as well as n6 and n3 PUFA elongase activities found in animals. cDNAs corresponding to C. elegans n3, ⌬12, ⌬6, and ⌬5 desaturase genes have been expressed in Arabidopsis and yeast to confirm their desaturase activity (8-11). Another C. elegans ...

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Section: Discussionmentioning

confidence: 99%

“…In humans, specific eicosanoid classes are derived from distinct C20 PUFA precursors (39). For example, series 1, 2, and 3 of prostaglandins are derived from 20:3n6, 20:4n6, and 20:5n3, respectively.…”

Section: Discussionmentioning

confidence: 99%

Genetic dissection of polyunsaturated fatty acid synthesis in Caenorhabditis elegans

Watts

Browse

2002

Proc. Natl. Acad. Sci. U.S.A.

358

411

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“…It is contains 60.0-70.0 % crude protein and is a rich source of vitamins (especially vitamin B 12 ), minerals, chlorophyll, carotenoids, carbohydrates, sterols, the pigments phycocyanin and allophycocyanin, which are mainly responsible for the antioxidant activities (Belay et al, 1996;Henrikson, 1997;Miranda et al, 1998) and some fatty acids, such as γ-linolenic acid (GLA, C18:3 n-6). This fatty acid (FA) has been shown to have important effects on several aspects of human health and nutrition (Fan and Chapkin, 1998).…”

Section: Introductionmentioning

confidence: 99%

Effects of diets with increasing levels of Spirulina platensis on the carcass characteristics, meat quality and fatty acid composition of growing rabbits

Peiretti

Meineri

2011

Livestock Science

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“…For example, they have been reported as having profound in¯uences in the CNS [25,64,69,99,159]. In addition, n-6 and n-3 PUFAs such as dihomo-gamma-linolenic acid (DGLAH20:3n-6), arachidonic acid (AAH20:4n-6) and eicosapentaenoic acid (EPA H 20:5n-3) are precursors for eicosanoids biosynthesis [35,108], which can exert a wide range of biological actions [53]. Whilst EPA content of membranes is a source for eicosanoid synthesis, DHA content may also play a contributory role, both directly and indirectly.…”

Section: Introductionmentioning

confidence: 99%

Essential fatty acids and the brain: possible health implications

Youdim

Martín

Joseph

2000

Intl J of Devlp Neuroscience

417

272

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Linoleic and a-linolenic acid are essential for normal cellular function, and act as precursors for the synthesis of longer chained polyunsaturated fatty acids (PUFAs) such as arachidonic (AA), eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), which have been shown to partake in numerous cellular functions aecting membrane¯uidity, membrane enzyme activities and eicosanoid synthesis. The brain is particularly rich in PUFAs such as DHA, and changes in tissue membrane composition of these PUFAs re¯ect that of the dietary source. The decline in structural and functional integrity of this tissue appears to correlate with loss in membrane DHA concentrations. Arachidonic acid, also predominant in this tissue, is a major precursor for the synthesis of eicosanoids, that serve as intracellular or extracellular signals. With aging comes a likely increase in reactive oxygen species and hence a concomitant decline in membrane PUFA concentrations, and with it, cognitive impairment. Neurodegenerative disorders such as Parkinson's and Alzheimer's disease also appear to exhibit membrane loss of PUFAs. Thus it may be that an optimal diet with a balance of n-6 and n-3 fatty acids may help to delay their onset or reduce the insult to brain functions which these diseases elicit. Published by Elsevier Science Ltd.

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Importance of Dietary γ-Linolenic Acid in Human Health and Nutrition

Cited by 321 publications

References 32 publications

Genetic dissection of polyunsaturated fatty acid synthesis in Caenorhabditis elegans

Genetic dissection of polyunsaturated fatty acid synthesis in Caenorhabditis elegans

Effects of diets with increasing levels of Spirulina platensis on the carcass characteristics, meat quality and fatty acid composition of growing rabbits

Essential fatty acids and the brain: possible health implications

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