The metabolism of dihomo‐γ‐linolenic acid in man

Stone, K. J.; Willis, A.L.; Hart, Mia van der; Kirtland, Stephen J.; Kernoff, P. B. A.; McNicol, G. P.

doi:10.1007/bf02533869

Cited by 131 publications

(37 citation statements)

References 14 publications

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“…In murine models, DGLA levels range from 0.2 to 5.8 pg/gm of tissue (29). In our studies, DGLA produced a statistically significant reduction of synovial cell growth at concentrations as low as 2 f l (0.6 pglml).…”

Section: Discussionmentioning

confidence: 52%

Suppression of human synovial cell proliferation by dihomo‐γ‐linolenic acid

Baker¹,

Krakauer²,

Tate³

et al. 1989

Arthritis & Rheumatism

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Prostaglandin E1 (PGE1) and oils enriched in its precursor fatty acids suppress inflammation and joint tissue injury in several animal models. Since synovial cell proliferation is a hallmark of rheumatoid arthritis, we studied the effect of dihomo‐γ‐linolenic acid (DGLA), an immediate precursor of PGE1, on the growth of human adherent synovial cells (ASC) in tissue culture. When stimulated by appropriate concentrations of recombinant interleukin‐1β (rIL‐1β), ASC proliferate and produce PGE. DGLA‐enriched medium suppressed both baseline and rIL‐1β–stimulated ASC growth fivefold, compared with medium supplemented with arachidonic acid. Indomethacin reduced the effect of the DGLA. Synovial cells incorporated the DGLA, and rIL‐1β–stimulated cells that were incubated with DGLA exhibited a 14‐fold increase in PGE1 (to 25.2 ± 6.0 ng/ml, mean ± SD) and a 70% decrease in PGE2 (to 25.2 ± 4.2 ng/ml) compared with cells in control medium. At equivalent concentrations (5 × 10−7M), PGE1 increased the level of cellular cAMP to a greater extent than did PGE2 (16.8 ± 2.0 pmoles versus 4.3 ± 1.9 pmoles, mean ± SEM). Exogenous PGE1 was also a more effective inhibitor of cell growth. Similarly, cAMP concentrations in cells exposed to DGLA for 6 hours were greater than concentrations in arachidonic acidenriched cultures (17.8 ± 3.3 pmoles versus 2.1 ± 2.0 pmoles). These observations suggest that DGLA can restrain ASC growth, an effect which may be due to its capacity to increase PGE1 production and subsequent cellular cAMP concentration.

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Section: Discussionmentioning

confidence: 52%

Suppression of human synovial cell proliferation by dihomo‐γ‐linolenic acid

Baker¹,

Krakauer²,

Tate³

et al. 1989

Arthritis & Rheumatism

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“…50 Finally and importantly, especially for investigating the role of n-6 and n-3 PUFA and their long chain derived products (ARA and DHA/EPA), desaturase activities are quite limited in the guinea-pig, and humans, while very active in other rodents. 51,52 Therefore, the guineapig appears to be a more relevant animal model than mice or rats for studying the effect of early nutrition, especially maternal nutrition, on adipose tissue development and the metabolic consequences later in life. Nevertheless, some limitations exist since few molecular and biochemical tools are available for this animal model.…”

Section: The Need For More Relevant Animal Modelsmentioning

confidence: 99%

Dietary fat and fat types as early determinants of childhood obesity: a reappraisal

et al. 2006

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Background: The growing prevalence of childhood overweight and obesity has renewed interest in determining the influence of the maternal and infant diet on the risk of developing excess fat mass later in life. Approach: Review of available human and animal data reporting the effects of dietary fat and fat types early in life on adipose development. Results: Rodent studies tend to show that maternal high-fat feeding during pregnancy and lactation results in increased adiposity of the offspring. Nevertheless, today there is a lack of population-based studies investigating this potential detrimental effect of maternal high-fat intake. Most epidemiological studies, performed so far, do not find any association between the level of dietary fat intake of infants and children and body weight and/or fatness. Regarding fat types exposure to high levels of dietary n-6 fatty acids during gestation and post-natal life, has been shown to promote obesity in mice. Nevertheless, other rodent studies do not demonstrate such an effect. Conclusion: There is no evidence supporting a restriction of fat intake during the first two post-natal years but the potential detrimental effects of maternal high-fat intake during gestation should be further investigated. The role of dietary fat types as early determinants of childhood obesity has so far been poorly studied. Robust evidence to support the adipogenic effects of n-6 fatty acids enriched-diets is currently lacking but this hypothesis is of importance and should be further evaluated in different animal models as well as in longitudinal human studies.

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“…Recently, a C 20 PUFA with three double bonds, dihomo-␥-linolenic acid (DGLA) (20:3n-6), has attracted great interest because it has unique biological activities in addition to its importance as a precursor of a large family of anti-inflammatory eicosanoids, such as series 1 prostaglandins and thromboxanes (6,9,12,17,18,20,34,39,41,45). C 20 fatty acids such as DGLA (20:3n-6) are synthesized by sequential desaturation and elongation of dietary LA (18:2n-6) (3,14,24,33).…”

mentioning

confidence: 99%

Heterologous Production of Dihomo-γ-Linolenic Acid in Saccharomyces cerevisiae

Yazawa

Iwahashi

Kamisaka

et al. 2007

Appl Environ Microbiol

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To make dihomo-␥-linolenic acid (DGLA) (20:3n-6) in Saccharomyces cerevisiae, we introduced Kluyveromyces lactis ⌬12 fatty acid desaturase, rat ⌬6 fatty acid desaturase, and rat elongase genes. Because Fad2p is able to convert the endogenous oleic acid to linoleic acid, this allowed DGLA biosynthesis without the need to supply exogenous fatty acids on the media. Medium composition, cultivation temperature, and incubation time were examined to improve the yield of DGLA. Fatty acid content was increased by changing the medium from a standard synthetic dropout medium to a nitrogen-limited minimal medium (NSD). Production of DGLA was higher in the cells grown at 15°C than in those grown at 20°C, and no DGLA production was observed in the cells grown at 30°C. In NSD at 15°C, fatty acid content increased up until day 7 and decreased after day 10. When the cells were grown in NSD for 7 days at 15°C, the yield of DGLA reached 2.19 g/mg of cells (dry weight) and the composition of DGLA to total fatty acids was 2.74%. To our knowledge, this is the first report describing the production of polyunsaturated fatty acids in S. cerevisiae without supplying the exogenous fatty acids.

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The metabolism of dihomo‐γ‐linolenic acid in man

Cited by 131 publications

References 14 publications

Suppression of human synovial cell proliferation by dihomo‐γ‐linolenic acid

Suppression of human synovial cell proliferation by dihomo‐γ‐linolenic acid

Dietary fat and fat types as early determinants of childhood obesity: a reappraisal

Heterologous Production of Dihomo-γ-Linolenic Acid in Saccharomyces cerevisiae

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