Thesis (Ph. D.)--West Virginia University, 2006. / Title from document title page. Document formatted into pages; contains viii, 123 p. : ill. (some col.). Includes abstract. Includes bibliographical references.

Cod hatcheries rely greatly on wild-caught broodstock as egg quality from farm-reared broodstock tends to be poor. Broodstock diet and levels of essential fatty acids have been linked to fecundity and egg quality in cod. Arachidonic acid (ARA) and astaxanthin (Ax) are important nutrients linked to fish egg quality and differences in levels have ben found between eggs from wild and farmed cod. The aim of this thesis was to investigate the impact of dietary supplementation with ARA and Ax on fecundity and egg quality in cod. The first experiment investigated the effect of feeding a diet supplemented with ARA, for 1, 2 or 3 months prior to peak spawning. Results showed that supplementation increased ARA in eggs and that Groups fed the supplement had improved fecundity and egg quality (though with no correlation between the duration of supplementation and number/quality of eggs). The second experiment investigated the effect of supplementation of Ax in broodstock diets on egg quality in farmed cod and showed that Ax was taken up into eggs and that fish fed supplemented diet had improved fecundity and egg quality. The third experiment compared the effect of diet supplementation with ARA and Ax on egg quality in wild and farmed cod and showed that despite the dietary supplementation, wild origin fish performed better on a number of egg quality and fecundity indices. However, it was not possible to take the greater ages and spawning experience of the wild broodstock into account, which may have influenced the results. The fourth experiment measured lipid and fatty acid profiles of eggs from two UK cod hatcheries. Variation was found between farms and across seasons. Results showed that supplementation of cod broodstock diet with ARA and Ax had a positive impact on egg quality and fecundity, although effects were not consistent across all egg quality parameters.

The major polyunsaturated fatty acid (PUFA) in the western diet is linoleic acid (LA), which is considered to be the major source of tissue arachidonic acid (AA), the principal precursor for the vaso-active eicosanoids via the cyclooxygenase enzymatic pathway. However, dietary AA may contribute significantly to tissue levels of AA in humans, leading to an increase in the production of eicosanoids, particularly the platelet aggregating, vasoconstricting, thromboxane (TXA2), hence increasing thrombosis risk. The aims of this study were to determine the extent to which dietary AA contributed to prostacyclin (PGI2) and TXA2 production in vivo and whether dietary long chain (LC) n-3 PUFA have a modulating influence on the metabolism of AA to these vaso-active eicosanoids. A gas chromatography -mass spectrometry (GCMS) method for urinary PGI2-M determination and a tandem GCMS/MS method for urinary TXA2-M determination were perfected for use within our laboratory (with the assistance of Dr Howard Knapp, University of Iowa and Professor Reinhard Lorenz, Ludwig Maximilian's University, Munich, respectively). An initial animal study compared the in vitro production of PGI2 by aorta segments with the whole body in vivo production of PGI2 in rats fed ethyl arachidonate or the ethyl ester of eicosapentaenoic acid (EPA), at levels many times higher than encountered in human diets. During AA feeding both measures of PGI2 increased, although in vitro TXA2 production was not affected. EPA feeding lowered in vitro TXA2 and in vivo PGI2. Prior to determining the effects of AA and LC n-3 PUFA in humans, a study was carried out to determine the AA and LC n-3 PUFA content of foods and from these, an estimate of the mean daily intake of AA and other LC PUFA. Eggs, organ meats and paté were found to be the richest sources of AA. Of the meat and fish analysed, white meat was found to be relatively rich in AA but poor in LC n-3 PUFA. Lean red meat, particularly kangaroo had similar LC n-3 PUFA and AA content. Fish, although rich in AA, had extremely high levels of LC n-3 PUFA. The calculated mean daily intakes of AA in Australian adults was 130mg (males) and 96mg (females). For total LC n-3 PUFA intake, the mean daily values were 247mg (males) and 197mg (females). Two human pilot studies involving dietary intervention trials examined the effects of dietary AA and AA plus long chain n-3 PUFA on thrombosis risk, gauged by the change in the ratio of PGI2 / TXA2 as well as alterations to other recognised risk factors, such as lipoprotein lipids and platelet aggregation. The desired dietary amounts of AA and LC n-3 PUFA were achieved in the first study by combining food items with known levels of each fatty acid. In the second study, where a diet with approximately equal quantities of AA and LC n-3 PUFA was being examined, kangaroo meat was consumed, following a low-fat vegetarian diet used as a baseline. Diets rich in AA alone (~500mg/day) increased plasma phospholipid (PL) AA levels, PGIi and TXA2 production. When foods containing equal quantities of AA and EPA (∼500mg/day of each) were fed to subjects PGI2 increased, with no change in TXAs production. Low fat vegetarian diets lowered PGI2 production, the level of which was reestablished by an AA rich diet (∼300mg AA/day + ∼260mg/day LC n-3 PUFA) of kangaroo meat. However, TXA2 production was not altered. A final, larger human dietary intervention trial then examined the effects of diets relatively rich in AA alone, AA plus LC n-3 PUFA and LC n-3 PUFA, on the ratio of PGI2/TXA2- The dietary sources of these fatty acids were white meat, red meat and fish, respectively. Each contained a mean level of AA of ∼140mg/day, with varying LC n-3 PUFA levels (59, 161 and 3380mg/day, respectively). Neither meat diet altered PGI2 or TXA2 production significantly, despite increasing serum PL AA levels. The fish diet resulted in a decrease in the serum and platelet PL AA/EPA ratio and TXA2 production, thus increasing the PGI2 / TXA2 ratio. These results would indicate that stores of AA in the body are sufficiently high to have effectively saturated the cyclooxygenase pathway for production of both PGI2 and TXA2, thus making any small change in the plasma level of AA due to 'normal' dietary levels, inconsequential. However, as seen in the rat study and the two pilot studies higher dietary levels of AA can increase both PGI2 and TXA2 production. Increases in platelet levels of EPA and DHA were associated with a decrease in TXA2 production, or the maintenance of a constant TXA2 level, while AA tissue levels and PGI2 production increased. This suggests a possible inhibitory effect of LC n-3 PUFA on the metabolism of AA to TXA2, particularly in platelets. From these short term studies, conducted over 2-3 week periods, it can be concluded that diets rich in lean meats can raise plasma AA levels but do not affect TXA2 or PGI2 production, hence are not pro-thrombotic. Diets rich in long chain n-3 PUFA from fish, raise plasma EPA and DHA levels, lower TXA2 production and are anti-thrombotic. Diets which combine equal quantities of AA and LC n-3 PUFA appear to increase PGI2 production while keeping TXA2 production constant. In order for these LC PUFA to have a significant effect on eicosanoid production the dietary intake of these fatty acids through foods such as red meat or white meat would have to be higher than average current Australian consumption levels.

Thesis (M.S.)--University of North Carolina at Wilmington, 2006. / Includes bibliographical references (leaves: 99-104)

Feline lipid metabolism is a topic for greater exploration due to this specie?s unique characteristics. Cats express limited Delta 6-desaturase activity necessary for conversion of linoleic acid (LA, 18:2n-6) to arachidonic acid (AA, 20:4n-6). The possibility exists that Gamma-linolenic acid (GLA, 18:3n-6) may serve as a precursor of AA in reproductive tissues especially if coupled with chain elongation and a functionally active Delta 5-desaturase. In addition no research has been conducted regarding feline reproductive Delta 8-desaturase activity as an alternate to the production of AA. To investigate desaturation activities, a group of 26 adult female cats were randomly assigned into 1 of 3 groups based on the diet fed: High Linoleic Acid (HL, n=7), Low Linoleic Acid (LL, n=9), and High Gamma-Linolenic Acid (GLA, n=10).The diets were fed for 300 days prior to ovariohysterectomy at which time EDTA plasma and ovarian, uterine, and subcutaneous adipose tissues were collected. Homogenates of each tissue were prepared and frozen in aliquots at -80 degrees C. Total lipids were extracted from the plasma and tissue homogenates followed by phospholipid (PL) fractionation via thin layer chromatography and fatty acid (FA) analyses by gas chromatography. The Shapiro-Wilks test was used to determine normal distribution of FA data followed by One-Way ANOVA and Tukey multiple comparisons (p<0.05). Plasma PLs were significantly increased in both GLA and dihomo-Gamma-linolenic acid (DGLA, 20:3n-6Delta8,11,14) in the GLA group and statistically increased in 20:2n-6 and 20:3n-6(Delta5,11,14) in the HL group. Uterine tissue homogenates had significantly increased amounts of DGLA and AA, however ovarian tissue showed an increase of only DGLA. Adipose tissue FAs showed significantly high amounts of DGLA in the GLA group. It is concluded that a high GLA diet results in increased AA in uterine, but not ovarian, tissues and thus may supply eicosanoid precursors in support of reproduction. The presence of increased amounts of 20:3n-6(Delta5,11,14) and not AA in the plasma and uterine tissues in the HL group suggests that Delta6-desaturase cannot be induced and that Delta8-desaturase is not active when feeding high dietary LA. Furthermore, the increase in DGLA may provide an adipose storage reservoir for additional conversion under times of metabolic need. These data support the presence of a functionally active Delta5-desaturase in uterine, but not ovarian, tissues. The findings also suggest that increased dietary GLA may be used to meet the AA requirements for reproduction in cats in the absence of an animal based pre-formed source of AA.

Thesis (Ph. D.)--University of Texas at Austin, 1999. / Vita. Greek alphabet delta in title. Includes bibliographical references (leaves 136-155). Available also in a digital version from Dissertation Abstracts.

It is widely accepted that prostaglandins (PGs), produced via the cyclooxygenase pathway from arachidonic acid, are essential to the ovulatory process in the pig. In support of this, ovulation is preceded by an increase in follicular fluid (FF) PG concentration, indomethacin (INDO) suppresses both the PG increase and ovulation, and ovulation can be restored by administration of exogenous PGs (Downey and Ainsworth, 1980; Prostaglandins 19: 17-22). Recent studies in the rat have shown that ovulation is also preceded by a rise in ovarian concentrations of 15-hydroxyeicosatetraenoic acid (15-HETE), a product of the lipoxygenase pathway (Tanaka et al., 1989; Endocrinology 15: 1373-1377) and inhibition of this pathway suppresses ovulation (Reich et al., 1983; Prostaglandins 26: 1011-1020). Furthermore, INDO, a cyclooxygenase inhibitor, inhibits 15-lipoxygenase as well as PG synthesis (Tanaka et al., 1989 Endocrinology 15: 1373-1377). The PMSG/hCG prepuberal gilt model was used to investigate the involvement of 15-HETE in the procine ovulatory process, and the effect of INDO on the 15-lipoxygenase pathway. Follicular fluid concentrations of 15-HETE were elevated 40 h post hCG (p $<$ 0.01). The effects of INDO and nordihydroguaiaretic acid (NDGA), an inhibitor of lipoxygenase activity, on ovulation rate, FF 15-HETE and FF PGF$ rm sb{2a}$ were investigated by intraovarian administration of INDO or NDGA. INDO inhibited ovulation rate (p $<$ 0.01) and PGF$ rm sb{2a}$ (p $<$ 0.01) as well as 15-HETE (p $<$ 0.01). NDGA also suppressed ovulation rate (p $<$ 0.01) but did not inhibit 15-HETE or PGF$ rm sb{2a}$ production. In in vitro experiments, 15-HETE production by both granulosa cell (GC) and theca interna cell (TIC) cultures 40 h post hCG was greater (p $<$ 0.01) than at 0 h post hCG. INDO inhibited 15-HETE production in 40 h post hCG TIC cultures (p $<$ 0.01) but not GC cultures, while NDGA inhibited 15-HETE production by both cell types (p $<$ 0.01). These results sugges

The secretory phospholipase A2 (sPLA2) family is a group of enzymes that catalyze the hydrolysis of glycerophospholipids at the sn-2 position, generating free fatty acids and lysophospholipids. The sPLA2 family has been implicated in various physiological and pathological activities. Eleven sPLA2’s have been identified in mammals, and the function of each isoform likely reflects its tissue distribution and substrate specificity. Studies in vitro indicate that Group X (GX) sPLA2 potently releases arachidonic acid (AA) and lysophosphatidylcholine from mammalian cell membranes. Interestingly, some of the biological effects mediated by GX sPLA2 in vitro are independent of its catalytic activity. Despite a wealth of in vitro data, the in vivo function of GX sPLA2 still remains to be elucidated. In order to define the function of GX sPLA2 in vivo, our laboratory recently generated C57BL/6 mice with targeted deletion of GX sPLA2 (GX-/- mice). When fed a normal rodent diet, GX-/- mice gained significantly more weight and had increased adiposity compared to GX+/+ mice, which was not attributable to alterations in food consumption or energy expenditure. When treated with adipogenic stimuli ex vivo, stromal vascular cells isolated from adipose tissue of GX-/- mice accumulated significantly more (20%) triglyceride compared to cells from GX+/+ mice. Conversely, overexpression of GX sPLA2, but not catalytically inactive GX sPLA2, resulted in a significant 50% reduction in triglyceride accumulation in OP9 adipocytes. The induction of adipogenic genes, including PPAR-γ, SREBP-1c, SCD-1 and FAS was also significantly blunted by 50-80% in OP9 cells overexpressing GX sPLA2. Activation of the liver X receptor (LXR), a nuclear receptor known to upregulate adipogenic gene expression, was suppressed in 3T3-L1 and OP9 cells when GX sPLA2 was overexpressed. Thus, hydrolytic products generated by GX sPLA2 negatively regulate adipogenesis, possibly by suppressing LXR activation.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2005. / Härtill 7 uppsatser.

Diss. (sammanfattning) Umeå : Umeå universitet, 2005. / Härtill 4 uppsatser.