Metabolic interactions between vitamin A and conjugated linoleic acid

Lipid-soluble molecules share several aspects of their physiology due to their common adaptations to a hydrophilic environment, and may interact to regulate their action in a tissue-specific manner. Dietary conjugated linoleic acid (CLA) is a fatty acid with a conjugated diene structure that is found in low concentrations in ruminant products and available as a nutritional supplement. CLA has been shown to increase tissue levels of retinol (vitamin A alcohol) and its sole specific circulating carrier protein retinol-binding protein (RBP or RBP4). However, the precise mechanism of this action has not been elucidated yet. Here, we provide a summary of the current knowledge in this specific area of research and speculate that retinol and CLA may compete for catabolic pathways modulated by the activity of PPAR- and RXR heterodimer. We also present preliminary data that may position PPAR- at the crossroads between the metabolism of lipids and vitamin

Low Sucrose, Omega-3 Enriched Diet Has Region-Specific Effects on Neuroinflammation and Synaptic Function Markers in a Mouse Model of Doxorubicin-Based Chemotherapy

Chemotherapeutic agents such as doxorubicin may negatively affect long-term brain functioning in cancer survivors; neuroinflammation may play a causal role. Dietary approaches that reduce inflammation, such as lowering sucrose and increasing eicosapentaenoic acid plus docosahexaenoic acid (EPA + DHA), may attenuate chemotherapy-induced neuroinflammation and synaptic damage, thereby improving quality of life. Ovariectomized, C57BL/6 mice were assigned to a chemotherapy (9 mg/kg doxorubicin + 90 mg/kg cyclophosphamide) or vehicle two-injection regimen, with injections two and four weeks after starting diets. In Study 1, mice received low sucrose diets with EPA + DHA or No EPA + DHA for four to six weeks; tissues were collected four, seven, or 14 days after the second injection. Compared to vehicle, chemotherapy increased pro-inflammatory cytokine IL-1β at day seven in the cortex and hippocampus, and reduced gene expression of synaptic marker Shank 3 at all timepoints in cortex, while EPA + DHA increased expression of Shank 3. In Study 2, high or low sucrose/EPA + DHA or No EPA + DHA diets were fed for five weeks; tissues were collected ten days after the second injection. Among chemotherapy-treated mice, brain DHA was higher with low sucrose feeding. Furthermore, low sucrose increased gene expression of Shank 1, while EPA + DHA increased expression of Shank 3 and reduced protein concentrations of pro-inflammatory markers IL-5, IL-6 and KC/GRO in the cortex, but not the hippocampus. Low sucrose, EPA + DHA diets may attenuate neuroinflammation and synaptic damage induced by doxorubicin-based chemotherapy in specific brain regions

Low Sucrose, Omega-3 Enriched Diet Has Region-Specific Effects on Neuroinflammation and Synaptic Function Markers in a Mouse Model of Doxorubicin-Based Chemotherapy

Chemotherapeutic agents such as doxorubicin may negatively affect long-term brain functioning in cancer survivors; neuroinflammation may play a causal role. Dietary approaches that reduce inflammation, such as lowering sucrose and increasing eicosapentaenoic acid plus docosahexaenoic acid (EPA + DHA), may attenuate chemotherapy-induced neuroinflammation and synaptic damage, thereby improving quality of life. Ovariectomized, C57BL/6 mice were assigned to a chemotherapy (9 mg/kg doxorubicin + 90 mg/kg cyclophosphamide) or vehicle two-injection regimen, with injections two and four weeks after starting diets. In Study 1, mice received low sucrose diets with EPA + DHA or No EPA + DHA for four to six weeks; tissues were collected four, seven, or 14 days after the second injection. Compared to vehicle, chemotherapy increased pro-inflammatory cytokine IL-1β at day seven in the cortex and hippocampus, and reduced gene expression of synaptic marker Shank 3 at all timepoints in cortex, while EPA + DHA increased expression of Shank 3. In Study 2, high or low sucrose/EPA + DHA or No EPA + DHA diets were fed for five weeks; tissues were collected ten days after the second injection. Among chemotherapy-treated mice, brain DHA was higher with low sucrose feeding. Furthermore, low sucrose increased gene expression of Shank 1, while EPA + DHA increased expression of Shank 3 and reduced protein concentrations of pro-inflammatory markers IL-5, IL-6 and KC/GRO in the cortex, but not the hippocampus. Low sucrose, EPA + DHA diets may attenuate neuroinflammation and synaptic damage induced by doxorubicin-based chemotherapy in specific brain regions

Three peroxisome proliferator-activated receptor isotypes from each of two species of marine fish

The cloning and characterization of cDNAs and genes encoding three peroxisome proliferator-activated receptor (PPAR) isotypes from two species of marine fish, the plaice (Pleuronectes platessa) and the gilthead sea bream (Sparus aurata), are reported for the first time. Although differences in the genomic organization of the fish PPAR genes compared with their mammalian counterparts are evident, sequence alignments and phylogenetic comparisons show the fish genes to be homologs of mammalian PPARα, PPARβ/δ, and PPARγ. Like their mammalian homologs, fish PPARs bind to a variety of natural PPAR response elements (PPREs) present in the promoters of mammalian or piscine genes. In contrast, the mRNA expression pattern of PPARs in the two fish species differs from that observed in other vertebrates. Thus, PPARγ is expressed more widely in fish tissues than in mammals, whereas PPARα and β are expressed similarly in profile to mammals. Furthermore, nutritional status strongly influences the expression of all three PPAR isotypes in liver, whereas it has no effect on PPAR expression in intestinal and adipose tissues. Fish PPARα and β exhibit an activation profile similar to that of the mammalian PPAR in response to a variety of activators/ligands, whereas PPARγ is not activated by mammalian PPARγ-specific ligands. Amino acid residues shown to be critical for ligand binding in mammalian PPARs are not conserved in fish PPARγ and therefore, together with the distinct tissue expression profile of this receptor, suggest potential differences in the function of PPARγ in fish compared with mammals

Influence of dietary conjugated linoleic acid (CLA) on lipid and fatty acid composition in liver and flesh of Atlantic salmon (Salmo salar)

The aim of the present study was to determine the effects of conjugated linoleic acid (CLA) on lipid and fatty acid metabolism in Atlantic salmon. The overall objective being to test the hypotheses that CLA has beneficial effects in salmon including growth enhancement, improved flesh quality through decreased adiposity and lipid deposition thereby minimising detrimental effects of feeding high fat diets, and increased nutritional quality through increased levels of beneficial fatty acids including n-3 highly unsaturated fatty acids (HUFA) and CLA itself. Salmon smolts were fed diets containing two levels of fish oil (low, ~18% and high, ~34%) containing three levels of CLA (a 1:1 mixture of 9-cis,trans-11 and trans-10,cis-12. at 0, 1 and 2% of diet) for 3 months and the effects on growth performance, liver and muscle (flesh) lipid contents and class compositions, and fatty acid compositions determined. The diets were also specifically formulated to investigate whether the effects of CLA, if any, were more dependent upon absolute content of CLA in the diet (as percentage of total diet) or the relative level of CLA to other fatty acids. Dietary CLA in salmon smolts had no effect on growth parameters or biometric parameters. However, there was a clear trend of increased total lipid and triacylglycerol contents in both liver and flesh in fish fed CLA, particularly in fish fed the high oil diets. Finally, CLA was incorporated into tissue lipids, with levels in flesh being 2-fold higher than in liver, but importantly, incorporation in liver was at the expense of saturated and monounsaturated fatty acids whereas in flesh it was at the expense of n-3HUFA

Influence of Dietary Oil Content and Conjugated Linoleic Acid (CLA) on Lipid Metabolism Enzyme Activities and Gene Expression in Tissues of Atlantic Salmon (Salmo salar L.)

The overall objective is to test the hypothesis that conjugated linoleic acid (CLA) has beneficial effects in Atlantic salmon through affecting lipid and fatty acid metabolism. The specific aims of the present study were to determine the effects of CLA on some key pathways of fatty acid metabolism including fatty acid oxidation and highly unsaturated fatty acid (HUFA) synthesis. Salmon smolts were fed diets containing two levels of fish oil (low, ~18% and high, ~34%) containing three levels of CLA (a 1:1 mixture of 9-cis,trans-11 and trans-10,cis-12 at 0, 1 and 2% of diet) for 3 months. The effects of dietary CLA on HUFA synthesis and β-oxidation were measured and the expression of key genes in the fatty acid oxidation and HUFA synthesis pathways, and potentially important transcription factors, peroxisome proliferators activated receptors (PPARs), determined in selected tissues. Liver HUFA synthesis and desaturase gene expression was increased by dietary CLA and decreased by high dietary oil content. Carnitine palmitoyltransferase-I (CPT-I) activity and gene expression were generally increased by CLA in muscle tissues although dietary oil content had relatively little effect. In general CPT-I activity or gene expression was not correlated with β-oxidation. Dietary CLA tended to increase PPARα and β gene expression in both liver and muscle tissues, and PPARγ in liver. In summary, gene expression and activity of the fatty acid pathways were altered in response to dietary CLA and/or oil content, with data suggesting that PPARs are also regulated in response to CLA. Correlations were observed between dietary CLA, liver HUFA synthesis and desaturase gene expression, and liver PPARα expression, and also between dietary CLA, CPT-I expression and activity, and PPARα expression in muscle tissues. In conclusion, this study suggests that dietary CLA has effects on fatty acid metabolism in Atlantic salmon and on PPAR transcription factors. However, further work is required to assess the potential of CLA as a dietary supplement, and the role of PPARs in the regulation of lipid metabolism in fish

Heterologous expression of linoleic acid isomerase from Propionibacterium acnes and anti-proliferative activity of recombinant trans-10, cis-12 conjugated linoleic acid

The linoleic acid isomerase enzyme from Propionibacterium acnes responsible for bioconversion of linoleic acid to trans-10, cis-12 conjugated linoleic acid (t10, c12 CLA) was cloned and overexpressed in Lactococcus lactis and Escherichia coli, resulting in between 30 and 50 % conversion rates of the substrate linoleic acid to t10, c12 CLA. The anti-proliferative activities of the fatty acids produced following isomerization of linoleic acid by L. lactis and E. coli were assessed using the human SW480 colon cancer cell line. Fatty acids generated from both L. lactis and E. coli contained a mixture of linoleic acid and t10, c12 CLA at a ratio of ∼1.35 : 1. Following 5 days of incubation of SW480 cells with 5–20 μg ml−1 (17.8–71.3 μM) of the t10, c12 CLA, there was a significant (P<0.001) reduction in growth of the SW480 cancer cells compared with the linoleic acid control. Cell viability after treatment with the highest concentration (20 μg ml−1) of the t10, c12 CLA was reduced to 7.9 % (L. lactis CLA) and 19.6 % (E. coli CLA), compared with 95.4 % (control linoleic acid) and 31.7 % (pure t10, c12 CLA). In conclusion, this is believed to represent the first report in which recombinant strains are capable of producing CLA with an anti-proliferative potential

Lipophilic Compound-Mediated Gene Expression and Implication for Intervention in Reactive Oxygen Species (ROS)-Related Diseases: Mini-review

In addition to exhibiting antioxidant properties, conjugated linoleic acid (CLA) and vitamin E may modulate gene expression of endogenous antioxidant enzymes. Depending on cellular microenvironments, such modulation reflects either antioxidant or prooxidant outcomes. Although epidemiological/experimental studies have indicated that CLA and vitamin E have health promoting properties, recent findings from clinical trials have been inconclusive. Discrepancies between the results found from prospective studies and recent clinical trials might be attributed to concentration-dependent cellular microenvironment alterations. We give a perspective of possible molecular mechanisms of actions of these lipophilic compounds and their implications for interventions of reactive oxygen species (ROS)-related diseases