The hydrogenation of gamma-linolenic acid by pure cultures of two rumen bacteria.
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ABSTRACT:
SUBMITTER: Kemp P
PROVIDER: S-EPMC1152535 | biostudies-other | 1983 Nov
REPOSITORIES: biostudies-other
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Project description:Gamma-linolenic acid (GLA, 18:3n-6) is an omega-6 (n-6), 18 carbon (18C-) polyunsaturated fatty acid (PUFA) found in human milk and several botanical seed oils and is typically consumed as part of a dietary supplement. While there have been numerous in vitro and in vivo animal models which illustrate that GLA-supplemented diets attenuate inflammatory responses, clinical studies utilizing GLA or GLA in combination with omega-3 (n-3) PUFAs have been much less conclusive. A central premise of this review is that there are critical metabolic and genetic factors that affect the conversion of GLA to dihommo-gamma linolenic acid (DGLA, 20:3n-6) and arachidonic acid (AA, 20:4n-6), which consequently affects the balance of DGLA- and AA- derived metabolites. As a result, these factors impact the clinical effectiveness of GLA or GLA/(n-3) PUFA supplementations in treating inflammatory conditions. Specifically, these factors include: 1) the capacity for different human cells and tissues to convert GLA to DGLA and AA and to metabolize DGLA and AA to bioactive metabolites; 2) the opposing effects of DGLA and AA metabolites on inflammatory processes and diseases; and 3) the impact of genetic variations within the fatty acid desaturase (FADS) gene cluster, in particular, on AA/DGLA ratios and bioactive metabolites. We postulate that these factors influence the heterogeneity of results observed in GLA supplement-based clinical trials and suggest that "one-size fits all" approaches utilizing PUFA-based supplements may no longer be appropriate for the prevention and treatment of complex human diseases.
| S-EPMC4975646 | biostudies-literature
Project description:Gut microbiota regulate physiological functions in various hosts, such as energy metabolism and immunity. Lactic acid bacteria, including Lactobacillus plantarum, have a specific polyunsaturated fatty acid saturation metabolism that generates multiple fatty acid species, such as hydroxy fatty acids, oxo fatty acids, conjugated fatty acids, and trans-fatty acids. How these bacterial metabolites impact host physiology is not fully understood. Here, we investigated the ligand activity of lactic acid bacteria-produced fatty acids in relation to nuclear hormone receptors expressed in the small intestine. Our reporter assays revealed two bacterial metabolites of γ-linolenic acid (GLA), 13-hydroxy-cis-6,cis-9-octadecadienoic acid (γHYD), and 13-oxo-cis-6,cis-9-octadecadienoic acid (γKetoD) activated peroxisome proliferator-activated receptor delta (PPARδ) more potently than GLA. We demonstrate that both γHYD and γKetoD bound directly to the ligand-binding domain of human PPARδ. A docking simulation indicated that four polar residues (T289, H323, H449, and Y473) of PPARδ donate hydrogen bonds to these fatty acids. Interestingly, T289 does not donate a hydrogen bond to GLA, suggesting that bacterial modification of GLA introducing hydroxy and oxo group determines ligand selectivity. In human intestinal organoids, we determined γHYD and γKetoD increased the expression of PPARδ target genes, enhanced fatty acid β-oxidation, and reduced intracellular triglyceride accumulation. These findings suggest that γHYD and γKetoD, which gut lactic acid bacteria could generate, are naturally occurring PPARδ ligands in the intestinal tract and may improve lipid metabolism in the human intestine.
| S-EPMC9636582 | biostudies-literature
Project description:This study presents a first report on ruthenium-catalyzed asymmetric transfer hydrogenation (ATH) of levulinic acid (LA) to chiral γ-valerolactone (GVL). ATH of LA has been explored with Noyori's chiral catalyst (Ru-TsDPEN) in methanol solvent. Efficacy of ATH reaction of LA was investigated under different reactions conditions such as temperature, catalyst, and hydrogen donor concentration. The effect of various organic tertiary bases along with formic acid (FA) as a hydrogen donor was studied, and N-methylpiperidine with FA (1:1 molar ratio) was revealed as an efficient hydrogen donor for ATH of LA to GVL furnishing chiral GVL with complete conversion and 93% enantiomeric excess (ee). This operationally simple and mild ATH protocol was tested for practical applicability of ATH of LA obtained from biomass waste (rice husk and wheat straw) and furnished chiral GVL with 82% ee.
| S-EPMC6868911 | biostudies-literature
Project description:1. alpha-[U-(14)C]Linolenic acid was incubated with the rumen contents of sheep and the metabolic products were characterized by thin-layer chromatography, gas-liquid chromatography and absorption spectroscopy in the ultraviolet and infrared. 2. A tentative scheme for the biohydrogenation route to stearic acid is presented. The main pathway is through diconjugated cis-cis-cis-octadecatrienoic acid, non-conjugated trans-cis (cis-trans)-octadecadienoic acid and trans-octadecenoic acid, but other pathways are apparent. 3. Washed rumen micro-organisms possessed only a limited capacity to hydrogenate alpha-linolenic acid and oleic acid but the rate was greatly stimulated by a factor(s) present in the supernatant rumen liquor. 4. Pure cultures of Clostridium perfringens, Streptococcus faecalis, Escherichia coli and a coliform organism isolated from sheep faeces possessed negligible ability to hydrogenate unsaturated fatty acids compared with a mixed population of rumen micro-organisms. Butyrivibrio fibrisolvens slowly converted linoleic acid into octadecenoic acid.
| S-EPMC1264865 | biostudies-other
Project description:Mixed rumen micro-organisms, maintained in continuous culture readily incorporated labelled HCO3- and acetate into amino acids. Labelled propionate, in contrast, was utilized only for isoleucine biosynthesis, but failed to label other amino acids to any significant extent. Evidence was obtained showing that in these mixed, i.e. symbiotic, cultures foward tricarboxylic acid-cycle reactions only proceed to 2-oxoglutarate. 14C distribution in amino acids clearly shows that 2-oxoglutarate is not oxidized further by tricarboxylic acid-cycle enzymes. Instead, acetate is carboxylated to pyruvate which is then carboxylated to oxaloacetate. Oxaloacetate equilibrates with fumarate and thereby carbon atoms 1 and 4 as well as carbon atoms 2 and 3 are randomized. Evidence was also obtained for the carboxylation of propionate to 2-oxobutyrate, isovalerate to 4-methyl-2-oxopentanoate, phenylacetate and hydroxyphentlacetate to the corresponding phenyl- and hydroxyphenyl-pyruvic acids and succinate to 2-oxoglutarate. Of the amino acid precursors investigated, only 3-hydroxypyruvate, the precursor of serine, appeared to be synthesized via an oxidative step, i.e. 3-phosphoglyceric acid to 3-phosphohydroxypyruvic acid. Most 2-oxo precursors of amino acids in these organisms appear to be formed via reductive carboxylation of the precursor acid.
| S-EPMC1165750 | biostudies-other
Project description:The t9,c12,c15-C18:3 as an isomer of α-linolenic acid (c9,c12,c15-C18:3; ALA), has been recently detected in milk, but has not been found in the rumen. This study hypothesized that it may be a biohydrogenation product of ALA in rumen and aimed to explore whether it was present in the rumen and help to understand the rumen biohydrogenation mechanisms of ALA. The in vitro experiment included two treatments, a control check (CK group) with 50 µL ethanol added, and ALA group with 50 µL ethanol and 2.6 mg ALA (ALA addition calculated by 1.30% of dry matter base of diet); each sample of fermentation fluid had the composition of C18 fatty acids analyzed at 0, 0.5, 1, 2, 3, 4, 5, and 6 h. The results showed that no t9,c12,c15-C18:3 was detected in the CK group, but ALA addition increased the concentration of t9,c12,c15-C18:3 in fermentation fluid. The content of t9,c12,c15-C18:3 peaked 1 h after fermentation, then declined gradually. At 1 h, no t9c12c15-C18:3 was detected in the fermentation fluid of the CK treatment. The results suggested that ALA converted to the isomer t9,c12,c15-C18:3 through biohydrogenation in the rumen. The addition of ALA can also increase the concentration of t9,c12-C18:2, c9,t11-C18:2, c12-C18:1, t11-C18:1, t9-C18:1, and c6-C18:1 in fermentation fluid. It was concluded using an in vitro experiment that t9,c12,c15-C18:3 was a product of rumen biohydrogenation of ALA.
| S-EPMC8868468 | biostudies-literature
Project description:Contextγ-Linolenic acid (GLA) is an important constituent of anti-ageing supplements.ObjectiveThe current study investigates the anti-ageing effect of GLA in Sprague-Dawley rats.Materials and methodsGLA (0.1, 0.2, 0.4, 2, 10, 20 and 24 μM) was initially evaluated for its effect on the formation of advanced glycation end products (AGEs) in vitro. For in vivo assessment (1, 5 or 15 mg/kg), the rat model of accelerated ageing was developed using d-fructose (1000 mg/kg (i.p.) plus 10% in drinking water for 40 days). Morris water maze was used to evaluate impairment in learning and memory. The blood of treated animals was used to measure glycosylated haemoglobin (HbA1c) levels. The interaction of GLA with active residues of receptor of AGE (RAGE) was analyzed using AutoDock Vina.ResultsOur data showed that GLA inhibited the production of AGEs (IC50 = 1.12 ± 0.05 μM). However, this effect was more significant at lower tested doses. A similar pattern was also observed in in vivo experiments, where the effect of fructose was reversed by GLA only at lowest tested dose of 1 mg/kg. The HbA1c levels also revealed significant reduction at lower doses (1 and 5 mg/kg). The in silico data exhibited promising interaction of GLA with active residues (Try72, Arg77 and Gln67) of RAGE.ConclusionThe GLA, at lower doses, possesses therapeutic potential against glycation-induced memory decline.
| S-EPMC7012036 | biostudies-literature
Project description:The goal of this study was to compare the transcriptome profile (RNA-seq) of perinatal hearts of cardiomyocyte-specific RXRab-deficient (edKO) and WT mice, to identify genes that are controlled by the expression of the TF RXRa and RXRb.
2023-02-15 | GSE188991 | GEO
Project description:The aim of this study was to investigate the effect and the mechanism of gamma linolenic acid (GLA) treatment on human hepatocellular (HCC) cell lines. The human HCC cell line HuH7 was exposed to GLA. Cell proliferation and reactive oxygen species (ROS) generation including lipid peroxidation and apoptosis were compared. We then used a cDNA microarray analysis to investigate the molecular changes induced by GLA. GLA treatment significantly reduced cell proliferation, generated ROS, and induced apoptosis. After 24 h exposure of Huh7 cells to GLA, we identified several genes encoding the antioxidant proteins to be upregulated: heme oxygenase-1 (HO-1), aldo-keto reductase 1 family C1 (AKR1C1), C4 (AKR1C4), and thioredoxin (Trx). The HO-1 protein levels were overexpressed in Huh7 cells after GLA exposure using a Western blot analysis. Furthermore, chromium mesoporphyrin (CrMP), an inhibitor of HO activity, significantly potentiated GLA cytotoxicity. GLA treatment has induced cell growth inhibition, ROS generation including lipid peroxidation, and HO-1 production for antioxidant protection against oxidative stress caused by GLA in Huh7 cells. GLA treatment should be considered as a therapeutic modality in patients with advanced HCC.
| S-EPMC2901768 | biostudies-literature
Project description:Even after decades of research, the mechanism of neurodegeneration remains understudied, hindering the discovery of effective treatments for neurodegenerative diseases. Recent reports suggest that ferroptosis could be a novel therapeutic target for neurodegenerative diseases. While polyunsaturated fatty acid (PUFA) plays an important role in neurodegeneration and ferroptosis, how PUFAs may trigger these processes remains largely unknown. PUFA metabolites from cytochrome P450 and epoxide hydrolase metabolic pathways may modulate neurodegeneration. Here, we test the hypothesis that specific PUFAs regulate neurodegeneration through the action of their downstream metabolites by affecting ferroptosis. We find that the PUFA dihomo-γ-linolenic acid (DGLA) specifically induces ferroptosis-mediated neurodegeneration in dopaminergic neurons. Using synthetic chemical probes, targeted metabolomics, and genetic mutants, we show that DGLA triggers neurodegeneration upon conversion to dihydroxyeicosadienoic acid through the action of CYP-EH (CYP, cytochrome P450; EH, epoxide hydrolase), representing a new class of lipid metabolites that induce neurodegeneration via ferroptosis.
| S-EPMC10214511 | biostudies-literature