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Ovulation is a prostaglandin (PG)-dependent process. Although n-3 polyunsaturated fatty acids (PUFA) and conjugated linoleic acid (CLA) have differing effects in the body, both reduce PG synthesis. We hypothesized that dietary n-3 fatty acids and CLA would differentially alter ovarian PG profiles through reductions in expression of enzymes involved in PG biosynthesis resulting in enhanced ovulation. Our objectives were to determine how dietary stearidonic acid and eicosapentaenoic acid (EPA) at 0.3 g/100 g diet and mixed isomers of CLA at 0.7 g/100 g diet, human achievable levels with daily consumption of fish or beef and dairy products, respectively, would influence ovulation and ovarian cyclooxygenase-1 (COX-1) and COX-2 expression in ovulation-induced rats. After 27 days on diet and ovulation induction, ovaries were isolated and analyzed from 22 pups per diet. Eicosapentaenoic acid ingestion reduced ova release by 16% while increasing PGE(2) and PGF(2alpha) release without altering COX-1 or COX-2 expression. Conversely, ovarian COX-1 expression was increased 135% with stearidonic acid ingestion associated with increased PGF(2alpha) without altering PGE(2) or ova release. Conjugated linoleic acid ingestion reduced COX-2 expression to 65% of that in rats consuming control and EPA diets; however, without affecting ovulation or PGs. Although it is generally believed that the COX-2 is the primary COX involved in ovulation, these results demonstrated that the n-3 PUFA differently affect ovarian COX-1 expression and that this effect differs from CLA, which reduced COX-2 expression. Further, although ovarian PGF(2alpha) is the primary PG altered by dietary n-3 PUFA, n-3 PUFA differentially influence ovarian PG biosynthesis and can decrease ova release, possibly induced through constitutive COX-1 enzyme expression.

Previous studies have not addressed the effect of differing fat intake on the effectiveness of varying (n-3) polyunsaturated fatty acid (PUFA) ingestion in altering tissue composition and eicosanoid production. This study examined (n-3):(n-6) PUFA ratios of 0, 0.1:1, 0.2:1, 0.4:1, and 1:1 with total fat at 5, 10, 15, and 20 g/100 g of diet and (n-6) PUFA fixed at 1.5 g/100 g of diet on tissue composition and peritoneal cell eicosanoid response to an in vivo inflammatory stimulus in 240 mice. Both (n-3) PUFA and total fat intake influenced tissue composition and eicosanoid biosynthesis. Increased (n-3) PUFA intake was associated with an increase in tissue (n-3) PUFA and a decrease in long-chain (n-6) PUFA. Although hepatic tissue linoleic acid (LA) was not altered by (n-3) PUFA intake or changes in total fat, peritoneal cell LA increased in response to increasing total fat but was unaffected by changes in dietary (n-3) PUFA. Four-series leukotrienes (LT) decreased progressively with increased (n-3) PUFA at all fat intake levels. In addition, four-series LT decreased with increased total fat at low (n-3):(n-6) ratios (0 and 0.1). At high (n-3):(n-6) ratios (0.4 and 1.0) increasing dietary fat between the 5 and 15 g/100 g diets increased four-series LT synthesis, which reached a plateau between 15 and 20 g fat/100 g diets. Five-series LT production generally rose with increased (n-3) PUFA intake; this effect was most evident in mice fed the 5 g fat/100 g diet. Increasing total dietary fat at the three highest (n-3):(n-6) ratios (0.2, 0.4, 1.0) decreased five-series LT production. Elevated (n-3) PUFA and total fat intake exerted an additive effect with respect to prostacyclin (PGI(2)) production because it was reduced with increasing intakes of both. Compared with the mice consuming the no (n-3) 5 g/100 g diets, PGI(2) levels were reduced by 88% in mice consuming the highest total fat and (n-3) PUFA diets. At low fat intake (5 and 10 g/100 g diet), increasing the (n-3) PUFA intake was associated with a decrease in PGE(2) synthesis. However, unlike PGI(2), high fat intake reduced PGE(2) to basal levels with no further reduction induced by increased (n-3) PUFA intake.

This study assessed the effect of frequency of consumption of a diet containing 10 g fat/100 g, with a (n-3):(n-6) polyunsaturated fatty acid (PUFA) ratio of 0.5, on tissue fatty acid composition and eicosanoid synthesis in CD-1 mice. With greater (n-3) PUFA consumption frequency, hepatic and peritoneal cell (n-3) PUFA levels changed to 14.4 +/- 1.3 and 12.4 +/- 0.9 mol/100 mol, respectively, from 2.4 +/- 0.3 and 1.9 +/- 0.3 mol/100 mol in control animals consuming a diet without (n-3) PUFA. Hepatic and peritoneal cell (n-6) PUFA levels were reduced to 6.4 +/- 0.5 and 7.6 +/- 0.5 mol/100 mol, respectively, with daily (n-3) PUFA consumption, compared with 23.6 +/- 0.7 and 17.9 +/- 0.7 mol/100 mol in control animals. Prostaglandin E, 6-keto-prostaglandin F1 alpha, and 4-series sulfidopeptide leukotriene biosyntheses reflected frequency of (n-3) PUFA consumption, with daily (n-3) PUFA consumption reducing prostaglandin E, consumption of (n-3) PUFA every other day reducing 6-keto-prostaglandin F1 alpha, and (n-3) PUFA consumption every 3 d reducing leukotriene C4 and leukotriene E4. Leukotriene C5 and leukotriene E5 changed from undetectable in animals consuming the control diet to > 40% of total leukotriene production in animals consuming (n-3) PUFA daily. Daily to biweekly consumption of fish or fish oil [1.26-0.63 g/wk of (n-3) PUFA, 6-3% of energy] may be a means for changing eicosanoid production. Consumption of (n-3) PUFA less often than twice a week may not change eicosanoid synthesis.

Ingestion of modest amounts of n-3 polyunsaturated fatty acids (PUFA) (2.8% w/w) decreased plasma triglyceride levels in Syrian hamsters by 49%. This was associated with a 45% increase in hepatic carnitine palmitoyl transferase activity. Significantly, at this low level of n-3 PUFA intake, hepatic peroxisomal oxidation measured as CN- insensitive palmitoyl-CoA dependent NAD reduction was unaffected. Consumption of increasing amounts of dietary n-3 PUFA up to 2% (w/w) in hamster diets containing 15% fat, gradually decreased plasma triglycerides to 56% of the control levels. The diet induced changes in plasma triglyceride levels were highly correlated (r = -0.97, P less than 0.01) with changes in hepatic carnitine palmitoyl transferase activity. A gradual decrease up to 59% in hepatic phosphatidate phosphohydrolase activity with n-3 fatty acid consumption was also observed. The hypotriglyceridemic effects of moderate intakes of n-3 fatty acids are, therefore, associated with changes in key enzymes in hepatic triglyceride synthesis and mitochondrial oxidation, but not peroxisomal oxidation.

Male Syrian hamsters consumed diets containing incremental increases in dietary n-3 fatty acids from fish oil with either low (0.015% w/w) or moderate (0.1% w/w) dietary cholesterol content. Animals consuming diets containing moderate cholesterol, but not animals consuming diets containing low cholesterol, had increased plasma very low (VLDL)- and low density lipoprotein (LDL)-cholesterol levels with increasing fish oil consumption. The plasma concentration of high density lipoprotein (HDL)-cholesterol decreased by 43 and 32% with the consumption of the highest fish oil diets in the low and moderate dietary cholesterol groups, respectively. Hepatic LDL-receptor binding activity did not change with the consumption of low cholesterol diets, but gradually decreased with fish oil consumption in animals consuming the moderate cholesterol diets. Hepatic LDL-receptor binding and plasma LDL-cholesterol levels of the different dietary fish oil groups were highly correlated (r = -0.91). Fish oil consumption also caused an increase in hepatic free cholesterol but a decreased cholesteryl ester content. Therefore, in the Syrian hamster, the consumption of n-3 fatty acids increases LDL-cholesterol levels which can be partially explained by decreased hepatic LDL-receptor binding and this response to dietary n-3 fatty acids is dependent on the dietary cholesterol content. However, the effects of dietary n-3 fatty acids on HDL-cholesterol are independent of dietary cholesterol content.

An incremental increase in the dietary (n-3):(n-6) polyunsaturated fatty acid (PUFA) ratio from 0 to 1.93 in diets containing 15% fat (wt/wt) decreased the total (n-6) PUFA content of phospholipids of the liver and peritoneal cells (macrophage) in mice from 43.1 and 33.6 mol/100 mol to 16.0 and 12.3 mol/100 mol with a concomitant increase of 27.6 and 16.1 mol/100 mol in (n-3) PUFA, respectively. Consumption of (n-3) PUFA increased hepatic (n-3) PUFA levels without changing total PUFA (46.35 vs. 46.87 mol/100 mol), whereas macrophage PUFA levels were decreased. The synthesis of sulfidopeptide leukotrienes (SP-LT) (LTC4 and LTE4) was progressively reduced by increasing dietary (n-3) PUFA, i.e., there was a reduction of 76% in mice fed a diet containing a (n-3):(n-6) PUFA ratio of 1.93 compared with the control diet. The 5-series SP-LT (LTC5 and LTF5) were produced in all animals consuming (n-3) PUFA and accounted for 62% of all SP-LT synthesized in mice fed the diet containing a 1.93 (n-3):(n-6) PUFA ratio. Synthesis of 6-keto-prostaglandin F1 alpha decreased 81% in mice fed a diet containing a (n-3):(n-6) PUFA ratio of 1.93 whereas prostaglandin E2 synthesis decreased 44% in mice fed diets with (n-3):(n-6) ratios ranging from 0.41 to 1.93.