Progress 02/01/00 to 01/31/05
Outputs
The major objective of our research has been to evaluate the anti-atherogenic potential of dietary gamma-linolenic acid (GLA, 18:3n-6). Natural sources of GLA include plant seed oils of evening primrose oil which contain 8-10% by weight of GLA, blackcurrant (16-17%), borage (24-25%) and fungal oils, such as Mucor javanicus (16-19%). Our previous studies have demonstrated that dietary GLA is rapidly elongated in vitro and in vivo to dihomogamma-linolenic acid (DGLA, 20:3n-6) in murine macrophages. The elongated product, DGLA, is capable of enhancing production of macrophage-derived prostaglandin E1 (PGE1). This is noteworthy because PGE1 is a potent inhibitor of vascular smooth muscle cell (SMC) proliferation. Using a mouse peritoneal macrophage-aortic SMC co-culture model, we have demonstrated that dietary GLA generates a macrophage phenotype that inhibits SMC proliferation. Although GLA has no direct effect on vascular SMC proliferation, a macrophage-derived soluble
factor, PGE1, appears to mediate the growth inhibitory response. Since alteration of SMC proliferation is a pivotal factor implicated in the pathogenesis of atherosclerotic vessel disease, an evaluation of the effect of dietary GLA on lesion development and progression of atherosclerosis in vivo was warranted. We have hypothesized that dietary GLA can favorably modulate the atherogenic process by down modulation of aortic SMC proliferation in vivo. Therefore, we utilized the ApoE null mouse model to evaluate the effect of dietary GLA on aortic vessel wall medial layer thickness, the number of proliferating (PCNA positive) aortic smooth muscle cells in the vessel wall, and aortic lesion progression. Since dietary supplementation with n-3 PUFA has been implicated in the reduction of atherosclerosis in humans and animals, we also examined the combined effects of GLA and n-3 PUFA on these parameters. Our data demonstrate that GLA down-modulates aortic SMC proliferation and retards
atherosclerotic lesion progression in vivo.
Impacts
The elucidation of the mechanisms by which dietary polyunsaturated fatty acids influence chronic disease progression and therapy will lead to the establishment of dietary guidelines designed to reduce the incidence and severity of inflammatory/hyperproliferative diseases. One such preventative/palliative approach may involve the use of gammalinolenic acid supplementation.
Publications
- No publications reported this period
|
Progress 01/01/03 to 12/31/03
Outputs
The underlying mechanisms by which n-3 polyunsaturated fatty acids (PUFA) exert a chemopreventive effect in the colon have not been elucidated. Retinoid X receptors (RXR) are a family of nuclear receptors implicated in cancer chemoprevention. Since docosahexaenoic acid (DHA), an n-3 PUFA enriched in fish oil, reduces colonocyte proliferation and enhances apoptosis relative to n-6 PUFA-treated cells, we determined whether DHA can serve as a specific ligand for RXR alpha activation relative to n-6 PUFA in colonocytes. In a mammalian one-hybrid assay, immortalized mouse colonic (YAMC) cells were cotransfected with a yeast galactose upstream activating sequence (UAS)4-tk-Luciferase (Luc) reporter plasmid, plus either GAL4 DNA binding domain fused to RXRalpha, retinoic acid receptor alpha, or GAL4 alone, followed by an n-3, n-6, or n-9 fatty acid incubation. Luc activity levels were dose-dependently elevated only in n-3 PUFA (DHA)-treated RXRalpha. Since RXR homodimers and
RXR/peroxisome proliferator-activated receptors (PPARs) heterodimers bind consensus direct repeat (DR1) motifs, YAMC and NCM460 (a normal human colonic cell line), were respectively, cotransfected with RXR alpha and DR1-Luc, followed by different PUFA treatment. Luc activity levels were increased (P<0.05) only in DHA groups. The DHA-dependent induction of DR-1-Luc was reduced to basal levels upon RXR alpha antagonist-treatment, with no effect on PPAR gamma antagonist-treatment. A role for select RXR isoforms in colonocyte biology was also determined by examining nuclear receptor mRNA levels in rat colon following dietary lipid and carcinogen exposure over time. RXR alpha, RXR beta, and RXR gamma were detected in rat colonic mucosa, and the levels of RXR alpha and RXR gamma were elevated in fish oil (n-3 PUFA) vs corn oil (n-6 PUFA) fed animals after 16 wk. These data indicate that, RXR alpha, an obligatory component of various nuclear receptors, preferentially binds n-3 PUFA in
colonocytes, and that the nuclear receptor targets for PUFA in the colon are modulated by dietary lipid exposure.
Impacts
We have demonstrated for the first time that RXR, an obligatory component of a large number of nuclear receptors, is preferentially activated by DHA, an n-3 PUFA, in colonocytes. This raises the intriguing possibility that n-3 PUFA mediate growth inhibitory effects in the colon through the RXR subunit of nuclear receptor heterodimers. Additional studies are required in order to identify the genes that are immediate responders to this class of activated receptors.
Publications
- Y.Y. Fan, T.E. Spencer, N. Wang, M.P. Moyer and R.S. Chapkin. Chemopreventive n-3 fatty acids activate RXR alpha in colonocytes. Carcinogenesis 24:1-8, 2003.
|
Progress 01/01/02 to 12/31/02
Outputs
Previous studies showing dietary (n-3) polyunsaturated fatty acids (PUFA) attenuate T cell immune-mediated inflammatory diseases led us to hypothesize that (n-3) PUFA promote activation-induced cell death (AICD)in T cells. Since T cell subsets display a differential resistance to AICD, we compared the effects of (n-3) PUFA feeding on T cells stimulated in vitro to express different cytokine profiles. Mice were fed either diets lacking (n-3) PUFA (control) or (n-3) PUFA-containing diets for 14 days. Splenic T cells were stimulated with aCD3/aCD28, PMA/Ionomycin, or aCD3/PMA for 48 h, followed by reactivation with the same stimuli for 5 h. Apoptosis was measured using AnnexinV/propidium iodide. (n-3) PUFA were selectively incorporated into membrane phospholipid pools. Cytokine analyses revealed that (n-3) PUFA enhanced AICD only in T cells expressing a Th1-like cytokine profile following stimulation with PMA/Ionomycin compared to mice fed the (n-6) PUFA control diet
(p=0.0008). In contrast, no increase in apoptosis was seen in T cells stimulated with aCD3/PMA, which exhibited a Th2 cytokine profile. These data demonstrate that the ability of (n-3) PUFA to promote AICD is dependent upon the activation stimulus. In conclusion, we have identified a novel mechanism by which (n-3) PUFA modulate T cell mediated immunity by selective deletion of Th1-like cells while maintaining or enhancing the Th2 mediated humoral immune response.
Impacts
These results indicate that dietary GLA can suppress SMC proliferation in vivo and retard the development of diet-induced atherosclerosis in Apo E KO mice.
Publications
- R.S. Chapkin, J.L. Arrington, T.V. Apanasovich, R.J. Carroll and D .N. McMurray. Dietary n-3 PUFA affect TcR-mediated activation of purified murine T cells and accessory cell function in co-cultures. Clinical and Experimental Immunology 130:12-18, 2002.
|
Progress 01/01/01 to 12/31/01
Outputs
We have shown that n-3 polyunsaturated fatty acids reduce mitogen-driven lymphoproliferation and IL-2 production in splenic T cells. Since the dietary effect could be mediated directly on the response of the T cells to stimuli, or indirectly on the accessory cells (AC) in the mixed culture, we examined the contribution of the 2 cell types to the dietary suppression of T cell function. Mice were fed diets with various levels of docosahexaenoic acid (DHA), either safflower oil, fish oil at 2% and 4%, or 1% DHA for 2 wk. T cells were obtained from spleens and AC were from peritoneal lavage. T cells and AC from each diet group were co-cultured with the alternative cell type from every other diet group, for a total of 16 co-culture groups. Co-cultures were stimulated with either ConA or antibodies to the T cell receptor (TcR)/CD3 complex and the costimulatory molecule CD28 (aCD3/aCD28). Proliferation was measured 4 d later. Reduction of T cell proliferation in co-culture
was dependent upon DHA dose fed to mice from which the T cells were derived, irrespective of the diet of AC donors. The greatest effect on T cell activation was from the DHA diet (Ptrend=0.005). The effect was seen with direct stimulation of the T cell receptor (aCD3/aCD28), but not with ConA. A significant effect of DHA was also mediated via the source of AC (Ptrend=0.033), indicating that diet was affecting TcR-mediated T cell activation by both direct and indirect mechanisms.
Impacts
These results indicate that dietary GLA can suppress SMC proliferation in vivo and retard the development of diet-induced atherosclerosis in Apo E KO mice.
Publications
- No publications reported this period
|
Progress 01/01/00 to 12/31/00
Outputs
Studies were conducted to evaluate the anti-atherogenic effects of dietary gamma-linolenic acid (GLA) (primrose oil) in ApoE genetic knockout mice. Five wk old male mice were fed cholesterol-free diets containing 10% fat (wt/wt) as corn oil (CO) [control diet, 0 mol% GLA and n-3 PUFA], primrose oil (PO, 10 mol% GLA), fish oil-CO mix (FC; 9:1, wt/wt, 0 mol% GLA and 17 mol% n-3 polyunsaturated fatty acids, PUFA), or fish oil/PO mix (FP, 1:3, wt/wt, 8% GLA and 5 mol% n-3 PUFA) for 15 wk. Subsequently, diets were supplemented with cholesterol (1.25%, w/w) and sodium cholate (0.5%, w/w) and fed for an additional 10 and 16 wk. Plasma cholesterol and triglyceride levels were similar across all dietary groups at 20, 30 and 36 wk of age. Mice fed GLA-containing diets (PO and FP) had significantly (P<0.05) higher systemic levels of dihomogamma-linolenic acid, the elongated product of GLA, relative to CO and FC groups. Consumption of GLA (PO and FP diets) significantly reduced
(P<0.05) aortic vessel wall medial layer thickness at 20 and 30 wks. A parallel GLA-dependent suppression in the number of proliferating (PCNA positive) aortic smooth muscle cells was also observed. Diets containing either GLA or n-3 PUFA reduced (P<0.05) atherosclerotic lesion size.
Impacts
These results indicate that dietary GLA can suppress SMC proliferation in vivo and retard the development of diet-induced atherosclerosis in Apo E KO mice.
Publications
- Y-Y. Fan, K.S. Ramos and R.S. Chapkin. 2000. Dietary Gamma-Linolenic Acid Suppresses Aortic Smooth Muscle Cell Proliferaton and Modifies Atherosclerotic Lesions in ApoE-Knockout Mice.(Submitted for publication)
|
Progress 01/01/99 to 12/31/99
Outputs
We have demonstrated previously that dietary supplementation of mice with gamma-linolenic acid (GLA, 18:3n-6) modulates functional interactions between macrophages and vascular smooth muscle cells (SMCs) and downregulates SMC proliferation in vitro. In this study, we determined the ability of dietary GLA (primrose oil) and n-3 polyunsaturated fatty acids (fish oil) to: 1) ameliorate atherosclerotic aortic lesion development and progression in the apoE genetic knock-out mouse model, and 2) modulate SMC proliferation in the thoracic aorta. Male ApoE knock-out mice (5 wk old) were fed for 15 wk, cholesterol-free diets containing 10% fat (wt/wt) that consisted of corn oil (CO) [control diet, 0 mol% GLA or n-3 fatty acids], primrose oil (PO), fish oil-CO mix (FC; 9:1, wt/wt), or fish oil/PO mix (FP, 1:3, wt/wt). No major lesions were found in the thoracic aortas at any time point for any of the diets examined. Cholesterol (1.25%, wt/wt) and sodium cholate (0.5%, wt/wt)
were then added to the diets from 15 - 25 wk. While cholesterol/sodium cholate supplementation increased serum cholesterol levels, dietary lipids did not further influence plasma cholesterol or triglyceride levels. At 30 wks of age, mice fed the control CO diet developed large atherosclerotic lesions in the thoracic aorta. A reduced number of lesions was found in PO, FC and FP-fed mice. The average medial thickness of the aortic vessel wall in the CO and FC groups was significantly greater (P<0.05) than in PO and FP groups. In addition, mice fed GLA had fewer (P<0.05) proliferating SMCs in the aortic vessel wall. These results indicate that dietary GLA can suppress SMC proliferation in vivo and retard the development of diet-induced atherosclerosis.
Impacts
(N/A)
Publications
- R.S. Chapkin. 2000. Yang-Yi Fan and K.D. Ramos. Dietary GLA retards atherosclerotic progression. To be presented at the American Oil Chemists' Meeting, April 25, 2000, San Diego, CA.
- R.S. Chapkin. 1999. Reappraisal of the essential fatty acids. In: Fatty Acids in Food and Their Health Implications. (Chow, C.K. ed.), Marcel Dekker, Inc., 2nd edition. 557-568.
- Y.Y. Fan, K.S. Ramos and R.S. Chapkin. 1999. Dietary primrose oil containing gammalinolenic acid suppresses smooth muscle proliferation and reduces atheriosclerosis in Apo E knock-out mice. (Submitted for publication).
|
Progress 01/01/98 to 12/31/98
Outputs
Since dietary gammalinolenic acid, GLA, reduces smooth muscle cell, SMC, DNA synthesis and proliferation, Fan et al. Arterio. Throm. Vasc. Biol. 15, 1397 to 1403, 1995, we have hypothesized that this lipid source will favorably modulate the atherogenic process. However, it remains unclear whether dietary GLA affords a protective effect on atherosclerotic lesion progression in vivo. Therefore, apolipoprotein E knock out mice, 4 wk old, n=10 were fed diets containing 10% w,w corn oil, CO, control diet, 0 mol% GLA or primrose oil, PO, 10 mol% GLA with and without cholesterol, 1.25%, w,w for 27 wk. Mice fed the control CO diet developed 10 fold larger atherosclerotic lesions in the thoracic aorta, relative to PO-fed mice at the end of the 27 wk feeding period. The average medial layer thickness of the vessel wall in the CO group was 1.5 fold greater, P<0.05, that PO group. These results indicate that dietary GLA can retard the development of atherosclerosis.
Impacts
(N/A)
Publications
- Fan, Y. Y and R.S. Chapkin. 1998. Significance of dietary gamma-linolenic acid. Journal of Nutrition 128,1411-1414.
- Fan, Y. Y., K.S. Ramos and R.S. Chapkin. 1999. Modulation of atherogenesis by dietary gamma-linolenic acid. In, Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation and Related Diseases, 4. Honn, K.U., ed., Plenum Press, New York. (In press).
|
Progress 01/01/97 to 12/31/97
Outputs
The present studies were conducted to elucidate the mechanisms by which dietary GLA influences the ability of macrophages to modulate SMC growth programs. Resident peritoneal macrophages were isolated from C57BL6 female mice fed diets containing variable GLA compositions at 10 percent wt,wt, treated with various antibodies and co-cultured with cycling naive vascular SMC isolated from nonpurified diet fed mice. SMC proliferation and intracellular cAMP levels were measured after co-culture. In parallel experiments, cycling naive vascular SMC isolated from nonpurified diet fed mice were dosed with exogenous PGE1 for various periods, challenged with cycloheximide for 4 hr, 8-12 hr after PGE1 addition, and intracellular cAMP levels were measured at various time points. Macrophages isolated from mice fed GLA-enriched dietary oils significantly reduced SMC proliferation in co-culture compared to control, corn oil diet containing no GLA. Anti-PGE1 antiserum treatment, 1:50 or
1:100, blocked the ability of GLA-enriched macrophages to down-regulate SMC proliferation, a response reversed by exogenous PGE1 treatment. Macrophages isolated from mice fed GLA-enriched dietary oils elevated SMC intracellular cAMP levels in a biphasic fashion. In addition, exogenous PGE1, 1 nmol per L - 10 umol per L, exerted a similar biphasic cAMP response in SMC, and the second phase of cAMP elevation was antagonized by cycloheximide. In conclusion, dietary GLA enhances mouse macrophage-derived prostaglandin E1 which inhibits vascular smooth muscle cell proliferation.
Impacts
(N/A)
Publications
- C.A. Jolly, J.C. Laurenz, D.N. McMurray and R.S. Chapkin. 1996. Diacylglycerol and ceramide kinetics in primary cultures of activated T-lymphocytes. Immunology Letters 49:43-48.
- T.J. Weber, R.S. Chapkin, L.A. Davidson and K.S. Ramos. 1996. Modulation of protein kinase C-related signal transduction by 2,3,7,8-tetrachlorodibenzo-p-dioxin exhibits cell cycle-dependence. Archives of Biochemistry and Biophysics 328:227-232.
- Y.Y. Fan, K.S. Ramos and R.S. Chapkin. 1997. Dietary gamma-linolenic acid enhances release of macrophage-derived prostaglandin E1 leading to inhibition of mouse vascular smooth muscle cell proliferation. Journal of Nutrition 127:1765-1771.
- T.J. Weber, Y.Y. Fan, R.S. Chapkin and K.S. Ramos. 1997. Growth-related signaling in vascular smooth muscle cells is deregulated by TCDD during G0,G1 transition. Journal of Toxicology and Environmental Health 51:369-386.
- C.A. Jolly, Y.H. Jiang, R.S. Chapkin and D.N. McMurray. 1997. Dietary n-3 polyunsaturated fatty acid modulation of murine lymphoproliferation and interleukin-2 secretion: Correlation with alterations in diacylglycerol and ceramide mass. Journal of Nutrition 127:37-43.
|
Progress 01/01/96 to 12/30/96
Outputs
Macrophages are present in all stages of atherogenesis. It is the principal cellular inflammatory mediator in the atheromatous plaque microenvironment. We have successfully developed an in vitro macrophage-vascular smooth muscle cell co-culture model to examine the atherogenic potential of macrophages following dietary gamma-linolenic acid manipulation. Our data indicate that gamma-linolenic acid-enriched dietary oils enhance the ability of mouse macrophages to secrete prostaglandin E1, which elevates smooth muscle cell intracellular cAMP levels, and down-regulates vascular smooth muscle cell proliferation. Since vascular smooth muscle cell proliferation is a key event in the development of atherosclerotic lesions, our finding is significant in view of the potential role of dietary lipids to favorably modulate disease progression.
Impacts
(N/A)
Publications
- Chapkin, R.S., Fan, Y.Y. and Ramos. 1996. Impact of dietary v-linolenic acid on macrophage-smooth muscle cell interactions. Down-regulation of vascular smooth muscle cell DNA synthesis. In: v-Linolenic acid. Metabolism and its roles in nutr
- Fan, Y.Y., Chapkin, R.S. and Ramos, K.S. 1996. Dietary lipid source alters murine macrophague/vascular smoooth muscle cell interactions in vitro. J. nutr. 126:2083-2088.
- Fan, Y.Y., Ramos, K.S. and Chapkin, R.S. 1996. Cell cycle-related inhibition of mouse vascular smooth muscle cell proliferation by prostaglandin E1: Relationship between prostaglandin E1 and intracellular muscle cAMP levels. Prostaglandins
|
Progress 01/01/95 to 12/30/95
Outputs
We determined how dietary oils containing gamma-linolenic acid (GLA)(primrose oil) and long-chain n-3 fatty acids (fish oil) influence the ability of macrophages to modulate smooth muscle cell (SMC)DNA synthesis in vitro.Mice were fed one of 4 diets containing 10%(w/w) cornoil (CO), primrose oil (PO), fish-corn oil mix ;(FC, 9:1, w/w) or fish-primrose oil mix (FP, 1:3, w/w) for 2 wk. Resident peritoneal macrophages were isolated from these mice and seeded on a semi-permeable membrane with a 30 KDa cut-off. Macrophages were preincubated with or without 50 micromolar indomethacin (a cyclooxygenase inhibitor) or 50 micromolar L655,238 (a 5-lipoxygenase inhibitor) for 30 min, and subsequently co-cultured for 40 h with naive murine aortic SMCs grown on culture dishes. SMC DNA synthesis was inhibited by 28 and 60% in PO and FP diets containing 10.1 and 8.2% GLA, respectively, relative to the control CO diet containing no GLA or long chain n-3 fatty acids. A 4-fold increase
in the levels of PGE1 was observed in PO and FP groups relative to control CO group. Macrophage inhibition of SMC DNA synthesis and proliferation in GLA-enriched dietary groups was inhibited by indomethacin but not L655,238.Therefore, dietary oils containing GLA reduce SMC DNA synthesis and proliferation in a cyclooxygenase-dependent manner and therefore, may favorably modulate the atherogenic process.
Impacts
(N/A)
Publications
|
Progress 01/01/94 to 12/30/94
Outputs
Since vascular smooth muscle cells (SMCs) and macrophages are major reactive cell types in atherosclerosis, we have developed a co-culture system for studying the interactions between these cell types. In addition, our results indicate that the regulatory effects of macrophage-derived soluble factors on SMC DNA synthesis can be modulated by dietary fat source. This model system will be helpful in future studies designed to understand the mechanisms by which diet modulates macrophage atherogenic potential.
Impacts
(N/A)
Publications
|
Progress 01/01/93 to 12/30/93
Outputs
We have demonstrated that dietary gammalinolenic acid (GLA) can enhance macrophage prostaglandin E(subscript 1) (PGE(subscript 1)) biosynthesis. This is noteworthy in view of the anti-proliferative, anti-aggregatory and anti-inflammatory properties of this 20:3n-6-derived cyclooxygenase product. We have also clearly demonstrated the existence of multiple regulatory mechanisms by which macrophages control the release of metabolically elongated GLA, and hence PGE(subscript 1) biosynthesis. Finally, GLA had no prophylactic properties with regard to the zymosan-induced acute inflammation, although the effect on chronic inflammation was not determined. Having successfully addressed the three major aims of the proposal, we are now interested in determining the efficacy of dietary GLA to favorably modulate selected markers and mediators of arterial thrombosis and cardiovascular disease. This focus represents a logical extension of the original proposal's specific aims.
Impacts
(N/A)
Publications
|
Progress 01/01/92 to 12/30/92
Outputs
In order to precisely determine the biological role of fish oil derived constituents (n-3 polyunsaturated fatty acids), it is imperative that information on highly purified n-3 polyunsaturated fatty acids be evolved. Therefore, we studied the effects of a low-dose, short-term dietary supplementation with highly purified (n-3) ethyl esters with regard to murine T lymphocyte function. A 10-day dietary supplementation with low-dose, highly purified (n-3) fatty acid/ethyl esters was examined for effects on murine splenic lymphocyte function and membrane composition. Mice were fed diets containing either 3% safflower oil (SAF) ethyl esters, 2% SAF plus 1% eicosapentaenoic acid ethyl esters (EPA) (99% pure), or 2% SAF plus 1% docosahexaenoic acid ethyl esters (DHA) (97% pure). Fatty acid analysis of the lymphocyte membranes showed that membrane compositions of the EPA and DHA-fed mice were subsequently enriched with these (n-3) fatty acids. Concanavalin A - induced
lymphoproliferative assays (Con A 5 ug/ml and 10 ug/ml) revealed that splenic lymphocytes from the EPA group had significantly higher mitogenic responses relative to lymphocytes from the DHA or SAF groups (p<0.05). Macrophage-lymphocyte co-cultures demonstrated that the dietary effect on proliferation in response to Con A was influenced by lymphocyte source (p<0.05), but not macrophage source.
Impacts
(N/A)
Publications
|
Progress 01/01/91 to 12/30/91
Outputs
To delineate the metabolism of gamalinolenic acid (18:(n-6)) by macrophages, primary cultures of resident mouse peritoneal macrophages were incubated with ?(superscript 14)C18:3(n-6). At 3, 6 or 20 h, the majority (>85%) of the radiolabel was recovered in cell phospholipids. With increasing time of incubation, a relative reduction of (superscript 14)C in glycerphosphocholine (ChoGpl, 58.1% to 46.2%) was noted. This was offset by a corresponding increase in glycerophosphoethanolamine (EtnGpl) labeling (from 8.8% to 18.9%). There was also a time-dependent redistribution of (superscript 14)C from diacyl to ether-containing phospholipid subclasses in ChoGpl and EtnGpl. Analysis of cell extracts by reverse-phase HPLC following transmethylation demonstrated that 18:3(n-6) was extensively elongated (>80%) to dihomogammalinolenic acid (20:3(n-6)) by 3h. The major radiolabeled phospholipid molecular species in the diacyl (PtdCho) and alkylacylglycerophosphocholine (PakCho)
subclasses was 16:0-20:3 (n-6). In contrast, diacyl (PtdEtn) and alkenylacylglycerophosphoethanolamine (PlsEtn) subclasses contained primarily ?(superscript 14)C18:0-20:3(n-6) and 16:0-20:3(n-6), respectively. Macrophages prelabeled with ?(superscript 14)C?18:3(n-6) for 20 h and stimulated with calcium ionophore A23187 or zymosan synthesized ?(superscript 14)C?prostaglandin E(subscript 1) (PGE(subscript 1)).
Impacts
(N/A)
Publications
|
Progress 01/01/90 to 12/30/90
Outputs
The influence of gammalinolenic acid (18:3n-6) feeding on peritoneal macrophage phospholipid profiles was determined. Mice were fed complete diets supplemented with either corn oil, predominantly containing linoleic acid (18:2n-6), borage oil containing 18:2n-6 and 18:3n-6, fish/corn mixture containing 18:2n-6, 20:5n-3 and 22:6n-3, or fish/borage oil mixture containing 18:2n-6, 18:3n-6, 20:5n-3 and 22:6n-3. After two weeks, the fatty acid concentrations of glycerophosphoserine (GPS), glycerophosphoinositol (GPI), sphingomyelin (SPH), and phospholipid subclasses of glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE) were determined. We report for the first time that mouse peritoneal macrophage GPC contains primarily 1-O-alkyl-2-acyl (range from the dietary groups, 24.6-30.5 mol %) and 1,2-diacyl (63.2-67.2 mol %), and GPE contains 1-O-alk-1'-enyl-2-acyl (40.9-47.4 mol %) and 1,2-diacyl (44.2-51.2 mol %) subclasses. In general, fish oil feeding increased
macrophage 20:5n-3, 22:5n-3 and 22:6n-3 levels while simutaneously reducing 20:4n-6 in GPS, GPI, GPE and GPC subclasses except for 1-O-alk-1'-enyl-2-acyl GPC. Administration of 18:3n-6 rich diets (borage and fish/borage mixture) resulted in the accumulation of 20:3n-6 (2-carbon elongation product of 18:3n-6) in most phospholipids. In general, the combination of dietary 18:3n-6 and n-3 polyunsaturated fatty acids produced the highest 20:3n-6/20:4n-6 phospholipid fatty acid rations.
Impacts
(N/A)
Publications
|
Progress 01/01/89 to 12/30/89
Outputs
Research is focusing on the effect of dietary fat on macrophage (white blood cell) phospholipid homeostasis. Experiments currently in progress are focusing on: Chain elongation of eicosapentaenoic acid. Dietary fish oil modulation of macrophage leukotriene E(4) (LTE(4)) production and phagocytosis. Effect of fish oil feeding on macrophage choline and ethanolamine glycerophospholipid subclasses.
Impacts
(N/A)
Publications
|
|