linoleic-acid and 10-12-octadecadienoic-acid

We have previously demonstrated that oral administration of a metabolically active Bifidobacterium breve strain, with ability to form cis-9, trans-11 conjugated linoleic acid (CLA), resulted in modulation of the fatty acid composition of the host, including significantly elevated concentrations of c9, t11 CLA and omega-3 (n-3) fatty acids in liver and adipose tissue. In this study, we investigated whether a recombinant lactobacillus expressing linoleic acid isomerase (responsible for production of t10, c12 CLA) from Propionibacterium acnes (PAI) could influence the fatty acid composition of different tissues in a mouse model. Linoleic-acid-supplemented diets (2 %, w/w) were fed in combination with either a recombinant t10, c12 CLA-producing Lactobacillus paracasei NFBC 338 (Lb338), or an isogenic (vector-containing) control strain, to BALB/c mice for 8 weeks. A third group of mice received linoleic acid alone (2 %, w/w). Tissue fatty acid composition was assessed by GLC at the end of the trial. Ingestion of the strain expressing linoleic acid isomerase was associated with a 4-fold increase (P<0.001) in t10, c12 CLA in adipose tissues of the mice when compared with mice that received the isogenic non-CLA-producing strain. The livers of the mice that received the recombinant CLA-producing Lb338 also contained a 2.5-fold (albeit not significantly) higher concentration of t10, c12 CLA, compared to the control group. These data demonstrate that a single gene (encoding linoleic acid isomerase) expressed in an intestinal microbe can influence the fatty acid composition of host fat.

Topics: Adipose Tissue; Animals; Bifidobacterium; Diet; Fatty Acids; Feces; Gastrointestinal Transit; Intramolecular Oxidoreductases; Lactobacillus; Linoleic Acid; Linoleic Acids, Conjugated; Liver; Male; Mice; Mice, Inbred BALB C; Probiotics; Propionibacterium acnes; Recombinant Proteins

Conjugated linoleic acid (CLA) isomers are potent inhibitors of mammary tumor cell growth. Evidence suggests that CLA modulates essential fatty acid (EFA) metabolism; however, it is not clear which parts of this pathway are important regulatory points modulated by CLA. Enriched mixtures of D9-cis,11-trans (D9c,11t)- and D10-trans,12-cis (D10t,12c)-18:2 were used to assess outcome measures of EFA metabolism pertaining to membrane phospholipid incorporation, tumor cell growth, and prostaglandin E2 (PGE2) synthesis in the MDA-MB-231 mammary tumor cell line. Tumor cells were treated with linoleic acid (LA), an equal mixture (Mix), or enriched preparations of D9c,11t- or D10t,12c-18:2. Treatment with Mix or the enriched mixture of D10t,12c-18:2 significantly inhibited the synthesis of arachidonic acid (AA) from LA, resulting in increased levels of LA and decreased levels of AA in membrane phosphatidylcholine and phosphatidylethanolamine (P < 0.05). LA and AA levels were not altered in cells treated with enriched D9c,11t-18:2 and were similar to those in LA control treated cells. All CLA treatments reduced [3H]thymidine uptake, an indicator of tumor cell growth, by more than one-half relative to LA controls. MDA-MB-231 cells challenged with AA in the presence of all CLA mixtures resulted in significantly reduced PGE2 synthesis relative to controls treated with LA (P < 0.05). It is evident that individual isomers exert inhibitory effects at specific steps of EFA metabolism, which correspondingly leads to a reduction in PGE2 synthesis and, ultimately, tumor growth.

Topics: Analysis of Variance; Arachidonic Acid; Breast Neoplasms; Dinoprostone; Female; Glycerophospholipids; Humans; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Stereoisomerism; Time Factors; Tumor Cells, Cultured