Oleic acid, hydroxytyrosol and n-3 fatty acids collectively modulate colitis through reduction of oxidative stress and IL-8 synthesis; in vitro and in vivo studies.

Our recent study has demonstrated that medium chain triglycerides (MCT) and monounsaturated fatty acids potentiate the beneficial effects of fish oil on risk factors of cardiovascular disease. In the present study, we have investigated the influence of MCT or olive oil on the protective and mucosal healing ability of fish oil in ulcerative colitis using cell simulation and animal models. Caco-2 cells grown in medium chain fatty acids enriched medium has exaggerated t-butyl hydroperoxide induced cell damage, GSH depletion, and IL-1ß induced IL-8 synthesis, compared to the cells grown in oleic acid & hydroxytyrosol (OT) enriched medium. Further, combined treatment of cells with eicosapentaenoic acid, docosahexaenoic acid, and OT has remarkably attenuated the cell damage, and IL-8 synthesis, compared to individual treatments. To evaluate the effect of these lipid formulations in vivo, adult Wistar rats were fed diet enriched with high amount of medium chain triglycerides (MCT), virgin olive oil, or their combination with fish oil. Colitis was induced in rats using dextran sulfate sodium (DSS) for 7days followed by 10-days of recovery period. Rats of MCT group exhibit severe disease activity, higher levels of inflammatory cytokines in the colon compared to the olive oil group. Furthermore, there was persistent body weight loss, loose stools, higher levels of inflammatory cytokines in the rats of MCT group, even after DSS was withdrawn from drinking water. Conversely, fish oil has remarkably attenuated the DSS induced alterations in both MCT and olive oil diet groups with significantly greater effect in the olive oil group. Thus, MCT increase the susceptibility to colitis through oxidative damage and IL-8 synthesis in intestinal epithelial cells. The beneficial effects of virgin olive oil could be partially attributed to hydroxytyrosol. Combined treatment of hydroxytyrosol, oleic acid and n-3 fatty acids exhibit huge therapeutic benefits in colitis.

Maternal and neonatal dietary intake of balanced n-6/n-3 fatty acids modulates experimental colitis in young adult rats.

BACKGROUND: The imbalance of n-6 and n-3 polyunsaturated fatty acids in the maternal diet impairs intestinal barrier development and sensitizes the colon response to inflammatory insults in the young rats. With a view to overcoming this issue, we designed this study to investigate the effect of maternal and neonatal intake of different proportions of n-6/n-3 fatty acids on colon inflammation in the young adult rats. METHODS: Female Wistar rats were assigned into four groups, and each group fed one of four semisynthetic diets, namely n-6, low n-3, n-6/n-3 and n-3 fatty acids for 8 weeks prior to mating, during gestation and lactation periods. At weaning, the pups were separated from the dams and fed diet similar to the mothers. Colitis was induced on postnatal day 35, by administering 2 % dextran sulfate sodium in drinking water for 10 days. Colitis was assessed based on the clinical and inflammatory markers in the colon. Fatty acid analysis was done in liver, RBC, colon and spleen. RESULTS: A balanced n-6/n-3 PUFA diet significantly improved the body weight loss, rectal bleeding and mortality in rats. This was associated with lower myeloperoxidase activity, nitric oxide, prostaglandin E2, TNF-α and IL-6, IL-8, COX-2 and iNOS levels in the colon tissues. Fatty acid analysis has shown that the arachidonic acid/docosahexaenoic acid ratio was significantly lower in liver, RBC, colon and spleen in n-6/n-3 and n-3 diet groups. CONCLUSION: We demonstrate that balanced n-6/n-3 PUFA supplementation in maternal and neonatal diet alters systemic AA/DHA ratio and attenuates colon inflammation in the young adult rats.

Maternal supplementation of α-linolenic acid in normal and protein-restricted diets modulate lipid metabolism, adipose tissue growth and leptin levels in the suckling offspring.

BACKGROUND: Lipid quantity and quality have been shown to affect serum cholesterol, adipose and serum leptin levels during prenatal and postnatal dietary supplementation of adult rats. Maternal protein deficiency during pregnancy and lactation also affects polyunsaturated fatty acid (PUFA) levels in the offspring. The aim of the present study was to analyze the effect of α-linolenic acid (ALA; n-3) on n-3 PUFA accretion, lipid profile, leptin levels and adipose growth in normal and protein-restricted (deficient) dams and their suckling pups. METHODS: Garden cress oil rich in ALA (32%) was supplemented in the normal and protein-restricted (10%) diets and fed to rats for 8 weeks prior to gestation and during lactation. PUFA, cholesterol, triglycerides, leptin levels and retroperitoneal white adipose tissue weight (WAT) of the dams and the pups were analyzed at 3 weeks after delivery. RESULTS: The serum cholesterol levels were remarkably decreased (p < 0.01), and the n-3 PUFA levels were markedly increased (p < 0.05) in the pups of lactating normal and protein-deficient dams supplemented with ALA. Triglycerides were unaltered in the dams and the pups of different dietary groups. Serum leptin levels and relative WAT weights were lower (p < 0.01) in the pups of the ALA-supplemented normal and protein-deficient dams. CONCLUSION: Maternal supplementation of ALA in normal and protein-restricted diets modulates n-3 PUFA levels, cholesterol, leptin levels and also adipose growth in the suckling offspring.