linoleic-acid and 10-hydroxy-12-octadecenoic-acid

10-hydroxy-cis-12 octadecenoic acid (10-HOE) is a type of octadecenoic acid with a hydroxyl on the C

Topics: Bacterial Proteins; Bifidobacterium; Biotransformation; Hydro-Lyases; Linoleic Acid; Linoleic Acids, Conjugated; Oleic Acids; Species Specificity

10-oxo-trans-11-octadecenoic acid (KetoC) and 10-hydroxy-cis-12-octadecenoic acid (HYA) are long-chain fatty acids generated from linoleic acid by the gut lactic acid bacterium Lactobacillus plantarum. These fatty acids have been reported to have anti-inflammatory activity in the intestine. However, little is known about their effects in the brain. In this study, we aimed to investigate the effects of these fatty acids on lipopolysaccharide (LPS)-induced inflammatory processes in mouse microglial cells (BV-2 cells). KetoC and HYA inhibited LPS-induced nitric oxide (NO) production and suppressed the expression of inducible NO synthase in BV-2 cells. NO changes in these inhibitory effects were observed with AH7614, a G-protein coupled receptor 120 antagonist, or the peroxisome proliferator-activated receptors antagonists, GW6471 and GW9662. In addition, KetoC and HYA did not inhibit translocation of p65, a subunit of NF-κB, or IκB degradation. Similarly, no effect on p38 or JNK phosphorylation was observed. However, KetoC and HYA were found to inhibit ERK phosphorylation induced by LPS, suggesting that these fatty acids may exert their anti-inflammatory effects through the inhibition of ERK activation in microglial cells.

Topics: Animals; Anti-Inflammatory Agents; Cells, Cultured; Depression, Chemical; Extracellular Signal-Regulated MAP Kinases; Fatty Acids, Unsaturated; Gastrointestinal Microbiome; Lactobacillus plantarum; Linoleic Acid; Lipopolysaccharides; Mice; Microglia; Nitric Oxide; Nitric Oxide Synthase Type II; Oleic Acids; Phosphorylation

The present study investigated the antiallergic and anti-inflammatory effects of 10-hydroxy-cis-12-octadecenoic acid (HYA), a novel gut microbial metabolite of linoleic acid, in NC/Nga mice, a model of atopic dermatitis (AD). Feeding HYA decreased the plasma immunoglobulin E level and skin infiltration of mast cells with a concomitant decrease in dermatitis score. HYA feeding decreased TNF-α and increased claudin-1, a tight junction protein, levels in the mouse skin. Cytokine expression levels in the skin and intestinal Peyer's patches cells suggested that HYA improved the Th1/Th2 balance in mice. Immunoglobulin A concentration in the feces of the HYA-fed mice was approximately four times higher than that in the control mice. Finally, denaturing gradient gel electrophoresis of the PCR-amplified 16 S rRNA gene of fecal microbes indicated the modification of microbiota by HYA. Taken together, the alterations in the intestinal microbiota might be, at least in part, associated with the antiallergic effect of HYA.

Topics: Animal Feed; Animals; Behavior, Animal; Cytokines; Dermatitis, Atopic; Diet; Dietary Supplements; Feces; Gastrointestinal Microbiome; Gene Expression Regulation; Immunoglobulin A; Inflammation; Linoleic Acid; Mice; Molecular Structure; Oleic Acids; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction

Linoleic acid Δ9 hydratase, which is involved in linoleic acid saturation metabolism of Lactobacillus plantarum AKU 1009a, was cloned, expressed as a his-tagged recombinant enzyme, purified with an affinity column, and characterized. The enzyme required FAD as a cofactor and its activity was enhanced by NADH. The maximal activities for the hydration of linoleic acid and for the dehydration of 10-hydroxy-cis-12-octadecenoic acid (HYA) were observed at 37 °C in buffer at pH 5.5 containing 0.5 M NaCl. Free C16 and C18 fatty acids with cis-9 double bonds and 10-hydroxy fatty acids served as substrates for the hydration and dehydration reactions, respectively. The apparent Km value for linoleic acid was estimated to be 92 μM, with a kcat of 2.6∙10(-2) s(-1) and a Hill factor of 3.3. The apparent Km value for HYA was estimated to be 98 μM, with a kcat of 1.2∙10(-3) s(-1).

Topics: Biocatalysis; Flavin-Adenine Dinucleotide; Hydrogen-Ion Concentration; Hydrolases; Kinetics; Lactobacillus plantarum; Linoleic Acid; Lipid Metabolism; NAD; Oleic Acids; Substrate Specificity; Temperature

Gut microbial metabolites of polyunsaturated fatty acids have attracted much attention because of their various physiological properties. Dysfunction of tight junction (TJ) in the intestine contributes to the pathogenesis of many disorders such as inflammatory bowel disease. We evaluated the effects of five novel gut microbial metabolites on tumor necrosis factor (TNF)-α-induced barrier impairment in Caco-2 cells and dextran sulfate sodium-induced colitis in mice. 10-Hydroxy-cis-12-octadecenoic acid (HYA), a gut microbial metabolite of linoleic acid, suppressed TNF-α and dextran sulfate sodium-induced changes in the expression of TJ-related molecules, occludin, zonula occludens-1, and myosin light chain kinase. HYA also suppressed the expression of TNF receptor 2 (TNFR2) mRNA and protein expression in Caco-2 cells and colonic tissue. In addition, HYA suppressed the protein expression of TNFR2 in murine intestinal epithelial cells. Furthermore, HYA significantly up-regulated G protein-coupled receptor (GPR) 40 expression in Caco-2 cells. It also induced [Ca(2+)]i responses in HEK293 cells expressing human GPR40 with higher sensitivity than linoleic acid, its metabolic precursor. The barrier-recovering effects of HYA were abrogated by a GPR40 antagonist and MEK inhibitor in Caco-2 cells. Conversely, 10-hydroxyoctadacanoic acid, which is a gut microbial metabolite of oleic acid and lacks a carbon-carbon double bond at Δ12 position, did not show these TJ-restoring activities and down-regulated GPR40 expression. Therefore, HYA modulates TNFR2 expression, at least partially, via the GPR40-MEK-ERK pathway and may be useful in the treatment of TJ-related disorders such as inflammatory bowel disease.

Topics: Animals; Caco-2 Cells; Colitis; Epithelial Cells; Female; Flow Cytometry; Humans; Immunohistochemistry; Intestines; Linoleic Acid; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; Oleic Acids; Receptors, G-Protein-Coupled

Specific isomers of conjugated linoleic acid (CLA), a fatty acid with potentially beneficial physiological and anticarcinogenic effects, were efficiently produced from linoleic acid by washed cells of Lactobacillus acidophilus AKU 1137 under microaerobic conditions, and the metabolic pathway of CLA production from linoleic acid is explained for the first time. The CLA isomers produced were identified as cis-9, trans-11- or trans-9, cis-11-octadecadienoic acid and trans-9, trans-11-octadecadienoic acid. Preceding the production of CLA, hydroxy fatty acids identified as 10-hydroxy-cis-12-octadecaenoic acid and 10-hydroxy-trans-12-octadecaenoic acid had accumulated. The isolated 10-hydroxy-cis-12-octadecaenoic acid was transformed into CLA during incubation with washed cells of L. acidophilus, suggesting that this hydroxy fatty acid is one of the intermediates of CLA production from linoleic acid. The washed cells of L. acidophilus producing high levels of CLA were obtained by cultivation in a medium containing linoleic acid, indicating that the enzyme system for CLA production is induced by linoleic acid. After 4 days of reaction with these washed cells, more than 95% of the added linoleic acid (5 mg/ml) was transformed into CLA, and the CLA content in total fatty acids recovered exceeded 80% (wt/wt). Almost all of the CLA produced was in the cells or was associated with the cells as free fatty acid.

Topics: Aerobiosis; Gas Chromatography-Mass Spectrometry; Lactobacillus acidophilus; Linoleic Acid; Magnetic Resonance Spectroscopy; Oleic Acids

Two strains of Enterococcus faecalis isolated from the ovine rumen and known to hydrate oleic acid were shown to transform linoleic acid by hydration into two products. The products, identified as 10-hydroxy-12-octadecenoic acid and 13-hydroxy-9-octadecenoic acid, were formed during stationary phase in yields of 13% and 6% respectively. Yields increased to 22% and 14% when culture conditions were optimised. To our knowledge, this is the first report of 13-hydroxy-9-octadecenoic acid production by bacteria. During a search for further linoleic-acid-hydrating bacteria, a strain of Streptococcus bovis isolated from bovine faeces and the ruminal strain S. bovis JB1 were found to hydrate linoleic acid. Both strains formed only one product and the most rapid appearance occurred during exponential growth. The S. bovis product, identified as 13-hydroxy-9-octadecenoic acid, formed in a yield of 28%. This study provides the first information on linoleic acid hydration by ruminal bacteria.

Topics: Animals; Cattle; Chromatography, High Pressure Liquid; Colony Count, Microbial; Enterococcus faecalis; Linoleic Acid; Oleic Acid; Oleic Acids; Ruminants; Sheep; Stearic Acids; Streptococcaceae; Streptococcus bovis

Lactobacillus plantarum produced 10-hydroxy-12(Z)-octadecenoic acid (10-OHODA) from linoleic acid. It was suspected that 10-OHODA might be closely related to leukotoxin (9,10-epoxy-12-octa-decenoic acid (LTx)) which was regarded as a toxic and/or defensive substance in living beings. The cardiac effect of 10-OHODA, which was biosynthesized by Lactobacillus plantarum, on an isolated guinea-pig papillary muscle was determined. Its effect on the contractile force of the tissue preparations was examined both in terms of its concentration and the time of exposure. A decrease in muscular tension was observed immediately after administration of 10-OHODA at concentrations of 30, 100, and 300 microM. We also compared the effect of 10-OHODA on muscle tension with that of LTx and its isomer 12,13-epoxy-9-octadecenoic acid (LTx'). Each inhibitory effect on the contractile force of the papillary muscle was statistically significant in the concentration of 300 microM 5 min after administration compared to the control in the absence of each fatty acid, suggesting that 10-OHODA is likely to exert some influence on the circulatory system together with LTx and LTx'.

Topics: Animals; Chromatography, Gas; Chromatography, Thin Layer; Female; Gas Chromatography-Mass Spectrometry; Guinea Pigs; Heart; In Vitro Techniques; Lactobacillus; Linoleic Acid; Linoleic Acids; Oleic Acids