Browsing by Subject "n-3 PUFA"
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Item Effect of HZE radiation and diets rich in fiber and n-3 poly unsaturated fatty acids (n-3 PUFA) on colon cancer in rats(Texas A&M University, 2006-08-16) Glagolenko, Anna AnatolievnaThis study examines the carcinogenic effect of HZE radiation and protective effects of different types of diets against colon carcinogenesis in a rat model. The effect of HZE radiation on health state and colon cancer development was evaluated. HZE radiation was found to suppress food consumption (P<0.0001) leading to lower body weight gain of irradiated rats when compared to the non-irradiated rats (P<0.05). The animals exposed to HZE radiation were found to start dying and/or getting pathologies 11 weeks earlier and at the end of the study had morbidity/mortality rate 14.2% higher (P=0.0005) than non-irradiated rats. There was no significant effect of HZE radiation on colon cancer incidence. The effects of dietary fibers and oils on health state and colon carcinogenesis were evaluated. Morbidity/mortality was found to be delayed in rats fed with pectinbased diets when compared to cellulose-based diet, regardless of radiation treatment. Similarly, fish oil was found to beneficially affect health of the experimental animals when compared to corn oil. Ten- and twenty-week delayed morbidity/mortality for irradiated and non-irradiated groups, respectively, was observed for rats fed with fish oil-based diets when compared to corn oil-based diets. Fish oil was also found to significantly reduce colon tumor incidence and multiplicity in non-irradiated rats (P<0.05). A similar trend was observed for the irradiated animals. No significant effect of fiber on colon cancer incidence was found. Finally, the effect of diets on general health and colon cancer development was investigated. Rats fed with corn oil/cellulose diet started dying and/or getting a disease earlier than rats fed with other diets, regardless of radiation treatment. The effect of diet on colon cancer development was found to depend on radiation treatment. Thus, in the absence of radiation treatment fish oil/cellulose was found to significantly reduce tumor incidence and multiplicity when compared to corn oil/pectin diet (P<0.05). In the presence of radiation treatment fish oil/pectin was found to lower the values of tumor incidence and tumor multiplicity, though the data obtained were not significant.Item Involvement of PFKFB3/iPFK2 in the Effects of Leucine and n-3 PUFA in Adipocytes(2012-02-14) Halim, VeraStudies had shown that leucine supplementation increases insulin sensitivity and it has been studied that n-3 PUFA may have an anti-inflammatory effect in adipocytes. However, the extent to which dietary sources such as leucine and/or n-3 PUFA act through PFKFB3/iPFK2 to suppress adipocyte inflammatory response has not been studied; PFKFB3/iPFK2 is a regulator that links adipocyte metabolism and inflammatory responses. In this study, the involvement of PFKFB3/iPFK2 in the effects of insulin sensitizing and anti-inflammatory effect of leucine and/or n-3 PUFA are explored using cultured 3T3-L1 adipocytes including wild-type cells, PFKFB3-control cells (iPFK2-Ctrl) and PFKFB3-knockdown cells (iPFK2-KD). In iPFK2-Ctrl cells, leucine supplementation appears to have insulin-sensitizing effects through improving p-Akt/Akt insulin signaling, but have no effect on adiponectin expression, and appear to have limited anti-inflammatory effects. n-3 PUFA supplementation appears to have limited effects on both insulin sensitizing and anti-inflammatory effects in iPFK2-Ctrl. In contrast, n-3 PUFA exhibit pro-inflammatory expression in iPFK2-KD. The results of this study support the hypothesis that PFKFB3/iPFK2 is critically involved in insulin-sensitizing effects of leucine. This role of PFKFB3/iPFK2, however, appears to be independent of anti-inflammatory responses. Given this, it is likely that PFKFB3/iPFK2 only account, in part, for the beneficial effects of leucine. n-3 PUFA stimulate PFKFB3/iPFK2 activity in wild-type adipocytes. However, PUFA do not exhibit anti-inflammatory and insulin-sensitizing effects in controls. In contrast, n3-PUFA exhibit proinflammatory effects in iPFK2-KD cells. Taken together, PFKFB3/iPFK2 is involved, at least in part, in the effects of insulin sensitization of leucine and appears to protect adipocytes from inflammatory responses, which could be exacerbated by n-3 PUFA when PFKFB3/iPFK2 is disrupted.Item Molecular mechanisms of immunosuppressive effects of dietary n-3 pufa, curcumin and limonin on murine cd4+ t cells(2009-05-15) Kim, WookiThe molecular mechanisms of putative anti-inflammatory nutrients, i.e., fish oil, curcumin and limonin, were investgated with respect to CD4+ T cell function. Initially, using a DO11.10 mouse model which exhibits a transgenic T cell receptor specific to OVA 323-339 peptide, we demonstrated that dietary fish oil suppresses antigen-specific Th1 clonal expansion in vivo. Following immunization, the accumulation of adoptively transferred transgenic cells in wild type recipient mouse lymph nodes was suppressed. In addition, cell division analysis by carboxyfluorescein succinimidyl ester (CFSE) revealed that both total cell number in lymph nodes as well as cell division were decreased by fish oil. Since n-3 polyunsaturated fatty acids (PUFA), active long chain fatty acids in fish oil, elicit favorable effects on a variety of cell types, e.g., anti-tumor effect on colonocytes, amelioration of coronary heart disease and anti-inflammatory effects involving T cells, B cells, dendritic cells and macrophages, we postulated that a fundamental mechanism of action may explain the multiple effects observed. In a series of experiments described herein, we demonstrated that n-3 PUFA alters the formation/location of membrane subdomains, referenced to as lipid rafts. Specifically, lipid raft formation at the immunological synapse (IS) in CD4+ T cells was suppressed following membrane enrichment with n-3 PUFA. The alteration of lipid rafts down-regulated the localization of select signaling proteins, including F-actin, PKC? and PLC?-1, and phosphorylation of PLC?-1 at the IS. Consequently, CD4+ T cell proliferation was suppressed as assessed by CFSE analysis and radioactive thymidine incorporation. Phytochemicals have been used for chemopreventive and chemotherapeutic purposes. We examined the putative anti-inflammatory effects of curcumin (1%) and limonin (0.02%) with respect to CD4+ T cell function. Dietary curcumin and limonin suppressed NF-?B activation in CD4+ T cells. In addition, CD4+ T cell proliferation was modulated by 2% curcumin. We further investigated the combined therapeutic potential of phytochemicals and fish oil, containing n-3 PUFA. Interestingly, fish oil and limonin together significantly (P<0.05) suppressed T cell proliferation, whereas feeding either fish oil or limonin alone showed little effect. In summary, our data indicated that dietary fish oil alters proximal signaling of T cells by perturbing lipid raft formation. Curcumin and limoin are capable of suppressing NF-?B in T cells, thereby exhibiting a synergistic effect when combined with fish oil. Further studies are required to elucidate the relationship of dietary dose of active compoments with respect to mechanism of actions.Item N-3 Polyunsaturated Fatty Acids Reduce Th17 Differentiation by Decreasing Responsiveness to Interleukin-6 in Mice(2014-05-29) Allen, Marilyn JeanCD4^(+) effector T cell subsets (e.g., Th1, Th17) are implicated in autoimmune and inflammatory disorders such as multiple sclerosis, psoriasis and rheumatoid arthritis. For optimal activation, IL-6 induces Th17 polarization and signals through the membrane-bound signal transducer, gp130. Previously, we have demonstrated that n-3 polyunsaturated fatty acids (PUFA), when supplied in the diet or in fat-1 transgenic mice which generate n-3 PUFA de novo, suppress CD4^(+) T cell activation and differentiation into pathogenic Th17 cells. Here we report that n-3 PUFA alter the response of CD4^(+) T cells to IL-6 in a lipid raft membrane-dependent fashion. Na?ve splenic CD4^(+) T cells from fat-1 mice exhibited significantly lower surface expression of the IL-6 receptor (IL-6R). This membrane bound receptor is known to be shed upon cellular activation in response to antigen; however, the release of soluble IL-6R after treatment with anti-CD3 and anti-CD28 was not changed in fat-1 mice suggesting that the decrease in surface expression is not due to ectodomain release. We observed a significant decrease in the association of gp130 with lipid rafts in activated fat-1 CD4^(+) T cells and a 35% reduction in gp130 homodimerization, an obligate requirement for downstream signaling. The phosphorylation of STAT3, a downstream target of IL-6-dependent signaling, was also decreased in response to exogenous IL-6 in fat-1 CD4^(+) T cells. Our results suggest that n-3 PUFA suppress Th17 cell differentiation, in part, by reducing membrane raft-dependent responsiveness to IL-6, an essential polarizing cytokine.Item n-3 PUFA and Curcumin Modulate the Resolution of Murine Intestinal Inflammtion(2011-07-30) Jia, Qian 1980-Bioactive food components containing n-3 polyunsaturated fatty acids (PUFA) and curcumin modulate multiple determinants that link inflammation to cancer initiation and progression. In this dissertation, both transgenic and dietary mouse models were used to elucidate the effect of n-3 PUFA and curcumin treatment on murine intestinal inflammation. Specifically, fat-1 transgenic mice, which convert endogenous n-6 PUFA to n-3 PUFA in multiple tissues, exhibited a reduced number of colonic adenocarcinomas per mouse (1.05 plus/minus 0.29 versus 2.12 plus/minus 0.51, P = 0.033), elevated apoptosis (P = 0.03), and a decrease in n-6 PUFA?derived eicosanoids compared with wild-type (wt) mice in an azoxymethane (AOM) - dextran sodium sulfate (DSS) model. Following a 2-week recovery period after 5 days of DSS exposure, colonic inflammation and ulceration scores returned to pretreatment levels only in fat-1 mice. In addition, fat-1 vs wt mice exhibited decreased (P < 0.05) levels of CD3 , CD4 T helper, and macrophage cell numbers in the colon. The ability of n-3 PUFA to favorably modulate the resolution of intestinal inflammation in fat-1 mice was linked to an enhancement (P < 0.05) in the percentage of colonic lamina propria (cLP) CD4 FoxP3 cells and a decrease in both splenic and cLP Th17 cells (0.8 vs 1.2 percent in spleen, 1.4 vs 1.7 percent in colon) (P < 0.05) in fat-1 mice compared to wt. These results suggest that the antitumorigenic effect of n-3 PUFA may be mediated via its anti-inflammatory properties. The combined effect of n-3 PUFA and curcumin on DSS induced colitis was assessed in C57BL/6 mice. Addition of fish oil (FO) and/or curcumin to a corn oil (CO) based diet increased animal mortality compared to CO alone (P < 0.05). Consistently, following 1 or 2 cycles of DSS treatment, both dietary FO and curcumin promoted mucosal injury/ulceration compared to CO. However, compared to other diets, FO and curcumin combined feeding enhanced the resolution of chronic inflammation and suppressed (p < 0.05) a key inflammatory mediator, NF-kB, in colon mucosa. Mucosal microarray analysis revealed that dietary FO and curcumin differentially modulated the expression of genes induced by DSS treatment. These results suggest that dietary lipids and curcumin interact to regulate mucosal homeostasis and the resolution of chronic inflammation in the colon.