Menhaden Oil Diet Research Articles

Dietary Fatty Acid Saturation Modulates Sphingosine-1-Phosphate-Mediated Vascular Function

Sphingolipids, modified by dietary fatty acids, are integral components of plasma membrane and caveolae that are also vasoactive compounds. We hypothesized that dietary fatty acid saturation affects vasoconstriction to sphingosine-1-phosphate (S1P) through caveolar regulation of rho kinase. Wild type (WT) and caveolin-1-deficient (cav-1 KO) mice which lack vascular caveolae were fed a low-fat diet (LF), 60% high-saturated fat diet (lard, HF), or 60% fat diet with equal amounts of lard and n-3 polyunsaturated menhaden oil (MO). Weight gain of WT on HF and MO diets was similar while markedly blunted in cav-1 KO. Neither high-fat diet affected the expression of cav-1, rho, or rho kinase in arteries from WT. In cav-1 KO, MO increased the vascular expression of rho but had no effect on rho kinase. HF had no effect on rho or rho kinase expression in cav-1 KO. S1P produced a concentration-dependent constriction of gracilis arteries from WT on LF that was reduced with HF and restored to normal with MO. Constriction to S1P was reduced in cav-1 KO and no longer affected by a high-saturated fat diet. Inhibition of rho kinase which reduced constriction to PE independent of diet in arteries from WT and cav-1 KO only reduced constriction to S1P in arteries from WT fed MO. The data suggest that dietary fatty acids modify vascular responses to S1P by a caveolar-dependent mechanism which is enhanced by dietary n-3 polyunsaturated fats.

Effects of dietary menhaden oil on growth and reproduction in gilts farrowed by sows that consumed diets containing menhaden oil during gestation and lactation

In sows, n-3 fatty acids increase litter sizes, however, effects on gilt reproductive development have not been adequately studied. Moreover, not determined are effects of feeding n-3 fatty acids to sows on reproduction in offspring. The objective here was to determine effects of 4% dietary menhaden oil on growth and puberty in gilts farrowed by sows fed menhaden oil. Sows (n = 44) were assigned to: (1) control gestation and lactation diets, or (2) diets including menhaden oil. For primiparous sows only, total litter size and born alive were greater (P < 0.05) in females fed menhaden oil. Conversely, pigs from primiparous controls were heavier (P < 0.05) than pigs from primiparous sows fed menhaden oil (parity by diet interactions, P < 0.01). Diet did not affect (P > 0.20) other sow and litter characteristics. At weaning, 84 gilts from control- or menhaden oil sows were placed three gilts per pen and provided control diets or diets containing menhaden oil. Nursery and grow-finish feed intake and feed efficiency were similar (P > 0.21) for gilts from the different sows and weight gain was similar (P > 0.24) for gilts fed control or menhaden diets. Gilts fed menhaden oil tended to eat less in the nursery (1.18±0.08 kg v. 0.98±0.08 kg; P = 0.09) and overall (1.83±0.04 kg v. 1.72±0.04 kg; P = 0.06). Thus, overall feed to gain was greater (2.52±0.03 v. 2.33±0.03; P < 0.01) and nursery (2.12±0.04 v. 1.80±0.04; P = 0.10) and grow-finish (3.07±0.19 v. 2.58±0.19; P = 0.08) feed to gain tended to be greater, for control gilts. Age at puberty was greater (P = 0.02) for gilts from menhaden oil-fed sows (205.1±3.2 days) compared to gilts from controls (193.9±3.2 days) and tended to be greater (P = 0.09), for controls (203.5±3.2 days) compared to gilts fed menhaden oil (195.5±3.2 days). A tendency existed (P = 0.09) for greater follicular fluid in gilts fed menhaden oil, however, ovulation rate and ovarian, luteal and uterine weights were not affected by sow diet, gilt diet or the interaction (P > 0.23). Feeding gilts menhaden oil enhanced feed efficiency and hastened puberty onset. Gilts from sows consuming menhaden oil exhibited delayed puberty and retaining females from sows fed this feedstuff may be ill advised.

Dietary Fat Influences the Expression of Genes Related to Sterol Metabolism and the Composition of Cecal Microbiota and Its Metabolites in Rats.

Numerous studies have evaluated the composition of gut microbiota in experimental animals fed high-fat or low-fiber diets. However, few reports have focused on the effects of different fatty acid (FA) compositions on the diversity of gut microbiota and its metabolites. Therefore, the aim of this research was to investigate the effects of different dietary fats on liver mRNA expression levels of genes related to cholesterol and bile acid (BA) metabolism, as well as to investigate cecal microbiota composition and bacterial metabolites composition in rats. Four-week-old male Wistar/ST rats were fed a 15% fat diet for 30 days, including from different sources (soybean oil, lard, menhaden oil, or tuna oil). Then, the rats' cecal microbiota composition was determined by sequencing the 16S ribosomal RNA gene using next-generation sequencing. Lard diet drastically decreased the expression level of liver ATP-binding cassette subfamily G genes (Abcg5 and Abcg8 genes) compared with other diets. Menhaden oil diet increased the fecal BA excretion compared with soybean oil and lard diets. Fecal BA excretion tended to be positively correlated with the relative abundance of Firmicutes, and negatively correlated with the relative abundance of Bacteroidetes. These results have shown that dietary fats with different FA compositions have a different effect on the relative composition of cecal microbiota, and in particular, menhaden oil may have very different effects compared to other experimental fats. The effects of fish oils on the cecal microbiota may differ greatly depending on the ratio of EPA to DHA and the composition of FA other than n-3 polyunsaturated FA. Our results provided new insights on the way different dietary fat sources affect sterol metabolism and alter cecal microbiota composition in rats.

Short-term menhaden oil rich diet changes renal lipid profile in acute kidney injury.

Weanling male Wistar rats fed a choline-deficient diet develop acute kidney injury. Menhaden oil, which is a very important source of omega-3 fatty acids, has a notorious protective effect. The mechanism of this protection is unknown; one possibility could be that menhaden oil changes renal lipid profile, with an impact on the functions of biological membranes. The aim of this work was to study the renal lipid profile in rats fed a choline-deficient diet with menhaden oil or vegetable oil as lipids. Rats were divided into 4 groups and fed four different diets for 7 days: choline-deficient or choline-supplemented diets with corn and hydrogenated oils or menhaden oil. Serum homocysteine, vitamin B12, and folic acid were analyzed. Renal lipid profile, as well as the fatty acid composition of the three oils, was measured. Choline-deficient rats fed vegetable oils showed renal cortical necrosis. Renal omega-6 fatty acids were higher in rats fed a cholinedeficient diet and a choline-supplemented diet with vegetable oils, while renal omega-3 fatty acids were higher in rats fed a choline-deficient diet and a choline-supplemented diet with menhaden oil. Rats fed menhaden oil diets had higher levels of renal eicosapentaenoic and docosahexaenoic acids. Renal myristic acid was increased in rats fed menhaden oil. The lipid renal profile varied quickly according to the type of oil present in the diet.

Marine fish oils are not equivalent with respect to B-cell membrane organization and activation

We previously reported that docosahexaenoic-acid (DHA)-enriched fish oil (DFO) feeding altered B-cell membrane organization and enhanced B-cell function. The purpose of this study was to evaluate whether menhaden oil (MO) and eicosapentaenoic-acid (EPA)-enriched fish oil (EFO) alters B-cell function/phenotype similarly. Mice were fed control (CON), MO, EFO or DFO diets for 5weeks. We evaluated the fatty acid composition of B-cell phospholipids, membrane microdomain organization, ex vivo B-cell functionality and in vivo B-cell subsets. Red blood cells and B cells were found to be strongly (r>0.85) and significantly (P<.001) correlated for major n-3 and n-6 long-chain polyunsaturated fatty acids (LCPUFAs). Compared to CON, MO and DFO resulted in decreased clustering of membrane microdomains, whereas EFO increased clustering. All fish oil treatments had 1.12–1.60 times higher CD40 expression following stimulation; however, we observed 0.86 times lower major histocompatibility complex class II expression and 0.7 times lower interleukin (IL)-6 production from EFO, but 3.25 times higher interferon-γ from MO and 1.5 times higher IL-6 from DFO. By 90min of incubation, MO had 1.11 times higher antigen uptake compared to CON, whereas EFO was 0.86 times lower. All fish oil treatments resulted in decreasingly mature splenic and bone marrow B-cell subsets. We conclude that diets high in n-3 LCPUFAs may elicit similar B-cell phenotypes but different organizational and functional outcomes. More specifically, these data suggest that the EPA and DHA content of a diet influences immunological outcomes, highlighting the importance of understanding how specific n-3 LCPUFAs modulate B-cell development and function.

Effect of replacing dietary menhaden oil with pollock or soybean oil on muscle fatty acid composition and growth performance of juvenile Pacific threadfin (Polydactylus sexfilis)

Abstract This study investigated effect of different dietary lipid sources on juvenile Pacific threadfin (Polydactylus sexfilis), a tropical marine fish, based on growth performance, proximate composition of whole fish and muscle fatty acid composition. The objectives were 1) to compare the nutritional value of menhaden oil to pollock oil, a product generated by the Alaskan fish processing industry; and 2) to evaluate the potential of replacing pollock oil with soybean oil in diets for juvenile Pacific threadfin. Six experimental diets were formulated to contain 42% crude protein and 12% crude lipid including 4% lipid from fishmeal and 8% added oil. The 8% added oil was provided by menhaden oil pollock oil (P) or soybean (S) oil mixed with pollock oil. Diets containing the mixed oil were named as P8S0, P6S2, P4S4, P2S6, and P0S8 to denote the level of pollock oil (decreasing from 8 to 0%) and soybean oil (increasing from 0 to 8%). Pacific threadfin (average body weight of 18.6 g) were fed each of the experimental diets for 8 weeks. Growth performance, proximate composition of whole body and muscle were similar among fish fed with different diets. Pollock oil and menhaden oil were shown to have a similar effect on the nutritional composition of fish or tissue. In contrast, the diet containing 8% soybean oil significantly increased liver lipid content compared to the other test diets. The fatty acid composition of muscle reflected the dietary fatty acids. Fish fed the soybean oil diets exhibited significantly lower levels of n-3 long chain polyunsaturated fatty acid (n-3 LC-PUFA) and higher levels of 18:2n-6 and 18:3n-3 than those fed the fish oil diets. Results of this study suggest that pollock oil can replace menhaden oil without any adverse effect on growth performance or nutritional quality of fish. Total replacement of pollock oil with soybean oil had no detrimental effect on growth performance of juvenile Pacific threadfin but altered the fatty acid composition of fish muscle tissue. These results are useful in formulating practical feeds at reduced cost for Pacific threadfin culture. However, a longer term study will be needed to investigate whether the changes in muscle fatty acid composition will influence the welfare as well as the market value of Pacific threadfin.

Anticancer activity of fish oils against human lung cancer is associated with changes in formation of PGE2 and PGE3 and alteration of Akt phosphorylation

The beneficial effects of omega-3 fatty acids are believed to be due in part to selective alteration of arachidonate metabolism that involves cyclooxygenase (COX) enzymes. Here we investigated the effect of eicosapentaenoic acid (EPA) on the proliferation of human non-small cell lung cancer A549 (COX-2 over-expressing) and H1299 (COX-2 null) cells as well as their xenograft models. While EPA inhibited 50% of proliferation of A549 cells at 6.05 µM, almost 80 µM of EPA was needed to reach similar levels of inhibition of H1299 cells. The formation of prostaglandin (PG)E3 in A549 cells was almost threefold higher than that of H1299 cells when these cells were treated with EPA (25 µM). Intriguingly, when COX-2 expression was reduced by siRNA or shRNA in A549 cells, the antiproliferative activity of EPA was reduced substantially compared to that of control siRNA or shRNA transfected A549 cells. In line with this, dietary menhaden oil significantly inhibited the growth of A549 tumors by reducing tumor weight by 58.8 ± 7.4%. In contrast, a similar diet did not suppress the development of H1299 xenograft. Interestingly, the ratio of PGE3 to PGE2 in A549 was about 0.16 versus only 0.06 in H1299 xenograft tissues. Furthermore, PGE2 up-regulated expression of pAkt, whereas PGE3 downregulated expression of pAkt in A549 cells. Taken together, the results of our study suggest that the ability of EPA to generate PGE3 through the COX-2 enzyme might be critical for EPA-mediated tumor growth inhibition which is at least partly due to down-regulation of Akt phosphorylation by PGE3.

The protective effect of menhaden oil in the oxidative damage and renal necrosis due to dietary choline deficiency

Weanling rats fed a choline-deficient diet develop kidney oxidative damage, tubular and cortical kidney necrosis, renal failure and animal death. The effect of dietary menhaden oil was assayed on the mentioned sequence correlating oxidative stress with renal structure and function. Rats were fed ad libitum 4 different diets: (a) a choline-deficient diet with corn oil and sunflower hydrogenated oil as a source of fatty acids; (b) the same diet supplemented with choline; (c) a choline-deficient diet with menhaden oil as a source of fatty acids; and (d) the previous diet supplemented with choline. Animals were sacrificed at days 0, 2, 4 and 7. The histopathological study of the kidneys showed that renal necrosis was only observed at day 7 in choline-deficient rats receiving the vegetable oil diet, simultaneously with increased creatinine plasma levels. Homogenate chemiluminescence (BOOH-initiated chemiluminescence) and phospholipid oxidation indicate the development of oxidative stress and damage in choline-deficient rats fed vegetable oils as well as the protective effect of menhaden oil. Rats fed with the fish oil diet showed that oxidative stress and damage develop later, as compared with vegetable oil, with no morphological damage during the experimental period.

Menhaden oil administration to dogs treated with radiation for nasal tumors demonstrates lower levels of tissue eicosanoids

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or menhaden oil may reduce inflammatory eicosanoids (prostaglandin E₂, thromboxane B₂, leukotriene B₄, and 11-dehydro thromboxane B₂), matrix metalloproteinases (MMPs), and blood lactate in dogs with nasal carcinomas receiving radiation therapy. We hypothesized that menhaden oil would reduce inflammation from radiation damage and lower blood lactate levels in dogs with nasal carcinoma. In a randomized, double-blind, placebo-controlled clinical study, 12 dogs with malignant carcinomas of the nasal cavity were given dietary menhaden oil (DHA and EPA) or soybean oil (control) and then received radiation therapy. Megavoltage radiation was delivered in 18 fractions to a total dose of 56 Gy. Blood levels of DHA, EPA, insulin, glucose, lactic acid, and MMPs 2 and 9; resting energy expenditure; and inflammatory eicosanoids from nasal biopsies were measured throughout radiation therapy. Samples were obtained from each patient 1 week before the start of radiation therapy, at start of radiation, and 7, 18 (end of radiation therapy), and 42 days after radiation was initiated. Dogs that are fed with menhaden oil had significantly (P < .05) higher plasma concentration of DHA by 500% and EPA by 200% and had significantly lower tissue inflammatory eicosanoids and decreased resting energy expenditure by 20% when compared with controls. Increased plasma DHA was significantly associated (P < .05) with decreased plasma lactic acid and MMPs. These data may suggest that dietary fish oil could reduce some detrimental inflammatory eicosanoids and metabolic consequences of radiation therapy.

Fish oil diets alter the phospholipid balance, fatty acid composition, and steroid hormone concentrations in testes of adult pigs

The objective was to determine the effect of long-term dietary supplementation of two types of fish oil on lipid composition and steroidogenesis in adult pig testis. Twenty-four Duroc boars, aged 204.5 ± 9.4 d (body weight 128.1 ± 16.7 kg) received daily 2.5 kg of an iso-caloric basal diet supplemented with: 1) 62 g of hydrogenated animal fat (AF); 2) 60 g of menhaden oil (MO) containing 16% of eicosapentaenoic acid (EPA) and 18% of docosahexaenoic acid (DHA); or 3) 60 g of tuna oil (TO) containing 7% of EPA and 33% of DHA. After these diets were consumed for 7 mo, testicular hormones, phospholipid content, and fatty acid composition of individual phospholipids in testis were determined. Body and reproductive organ weights were not significantly affected by dietary treatments. Testicular tissue from boars fed a TO diet, followed by those receiving MO and AF diets, had the lowest level of phosphatidylethanolamine (TO < MO < AF; P < 0.01) but the highest sphingomyelin (TO > MO > AF; P < 0.01). For each phospholipid, boars fed either the MO or TO diet had increased total omega-3 fatty acids, particularly DHA (P < 0.01), by reciprocal replacement of total omega-6 fatty acids (20:4n-6, 22:5n-6). The MO diet increased EPA more than the other diets. Testicular concentrations of testosterone and estradiol were lower in boars fed a TO diet than a MO diet (P < 0.02). In conclusion, long-term dietary supplementation of fish oil, regardless of the EPA/DHA ratio, modified the fatty acid compositions in testis and affected steroid production of healthy adult boars, which may represent a promising models for future studies on fertility.

The effects of phase-feeding rainbow trout (Oncorhynchus mykiss) with canola oil and Alaskan pollock fish oil on fillet fatty acid composition and sensory attributes

Rainbow trout (186 g) were fed three test diets where the lipid source (150 g kg−1) was either menhaden oil (MO), pollock oil (PO) or canola oil (CO) for eight weeks to an average weight of 370 g. The CO group was then divided into two groups, one continuing on the CO diet and the other switched to the PO diet (CO–PO). After nine additional weeks of feeding, the average fish weight approximately doubled (719–749 g). No significant differences were found in average final weight or fillet yield among dietary treatment groups. Fatty acid profiles of fillets from trout fed MO, PO or CO-supplemented diets reflected the fatty acid profiles of the added oils, whereas the fatty acid profile of fillet from trout in the CO–PO group exhibited values similar to those of fish fed PO. The ratio of ω3 : ω6 FA was nearly 2.5 times higher in fillets from the CO–PO group compared to the CO group. Sensory analysis showed that panelists preferred CO-fed fillets over those fed MO, PO, or CO–PO. Phase-feeding CO and PO reduced fish oil use and resulted in fillets with double the content of Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) over CO-fed fish, similar to levels in MO-fed fish.

Effects of dietary menhaden oil, soybean oil and soybean lecithin oil at different ratios on growth, body composition and blood chemistry of juvenile Litopenaeus vannamei

A 10-week feeding experiment was conducted to evaluate the nutritional value of menhaden oil (MO), soybean oil (SO) and soybean lecithin oil (SL) at different ratios (MO/SO/SL) in practical diets for juvenile Litopenaeus vannamei by determining their effects on survival, growth, blood chemistry and fatty acid composition of hepatopancreas and muscle tissue. Eight isonitrogenous and isolipidic diets were formulated using 3% MO(3/0/0), 3% SO(0/3/0), 3% SL(0/0/3), 1% MO + 1% SO + 1% SL (1/1/1), 1% SO + 2% SL (0/1/2), 1% MO + 2% SL (1/0/2), 2% SO + 1% SL (0/2/1) and 2% MO +1% SL (2/0/1), respectively. There were no significant differences in body weight gain among all treatments. However, shrimp fed diets with SL supplementation showed significantly (P < 0.05) higher survival than those fed diets without SL supplementation (3% MO and 3% SO diets). The fatty acid (FA) composition of hepatopancreas and muscle tissue reflected, to a certain extent, FA composition of the test diets. Shrimp fed the 3% SL diets showed significantly (P < 0.05) higher triglyceride (TG) concentration in serum than those fed the other experimental diets. Shrimp fed diets containing SL have relatively higher total cholesterol (TC) and phospholipid (PL) concentration in serum than those fed the diets without SL (3% MO and 3% SO). The results of the present investigation are encouraging and confirmed soybean lecithin supplement in shrimp practical diets, when sufficiently high levels of phospholipid are present, survival is enhanced.

Regulation of glucose and protein metabolism in growing steers by long-chain n-3 fatty acids in muscle membrane phospholipids is dose-dependent

A previous study showed that long-chain n-3 polyunsaturated fatty acids (LCn-3PUFA; >18 carbons n-3) exert an anabolic effect on protein metabolism through the upregulation of insulin sensitivity and activation of the insulin signaling pathway. This study further delineates for the first time whether the anabolic effect of LCn-3PUFA on metabolism is dose responsive. Six steers were used to test three graded amounts of menhaden oil rich in LCn-3PUFA (0%, 2% and 4%; enteral infusions) according to a double 3 × 3 Latin square design. Treatment comparisons were made using iso-energetic substitutions of control oil for menhaden oil and using 6-week experimental periods. The LCn-3PUFA in muscle total membrane phospholipids increased from 8%, 14% to 20% as dietary menhaden oil increased. Feeding graded amounts of menhaden oil linearly decreased plasma insulin concentration (49, 35 and 25 μU/ml, P = 0.01). The insulin-stimulated amino acid disposal rates as assessed using hyperinsulinemic–euglycemic–euaminoacidemic clamps (20, 40 and 80 mU/kg per h) were linearly increased by the incremental administrations of menhaden oil from 169, 238 to 375 μmol/kg per h (P = 0.005) during the 40 mU/kg per h clamp, and from 295, 360 and 590 μmol/kg per h (P = 0.02) during the 80 mU/kg per h clamp. Glucose disposal rate responded according to a quadratic relationship with the incremental menhaden oil amounts (P < 0.05). A regression analysis showed that 47% of the amino acid disposal rates elicited during the hyperinsulinemic clamp was related to muscle membrane LCn-3PUFA content (P = 0.003). These results show for the first time that both protein and glucose metabolism respond in a dose-dependent manner to menhaden oil and to muscle membrane LCn-3PUFA.

Improved n-3 fatty acid status does not modulate insulin resistance in fa/fa Zucker rats

The objective was to examine the effect of polyunsaturated fatty acid type (plant vs fish oil-derived n-3, compared to n-6 fatty acids in the presence of constant proportions of saturated, monounsaturated and polyunsaturated fatty acids) on obesity, insulin resistance and tissue fatty acid composition in genetically obese rats. Six-week-old fa/fa and lean Zucker rats were fed with a 10% (w/w) mixed fat diet containing predominantly flax-seed, menhaden or safflower oils for 9 weeks. There was no effect of dietary lipid on obesity, oral glucose tolerance (except t=60 min insulin), pancreatic function or molecular markers related to insulin, glucose and lipid metabolism, despite increased n-3 fatty acids in muscle and adipose tissue. The menhaden oil diet reduced fasting serum free fatty acids in both fa/fa and lean rats. These data suggest that n-3 composition does not alter obesity and insulin resistance in the fa/fa Zucker rat model when dietary lipid classes are balanced.

Dietary menhaden oil and resistant starch interact to increase fermentation in large intestine

Dietary resistant starch (RS) and fish oil (FO) have been shown independently to reduce body fat in rats. RS may produce this effect through mechanisms and hormone secretions related to colonic fermentation pathways. The objective of this study was to determine additive or synergistic effects when combining Hi‐Maize© RS and Novomega© encapsulated menhaden FO (National Starch). Forty, 5‐week old female rats were free fed for a 4 week weight gain period. Prior to the next feeding period, rats were stratified by weight and placed in 4, energy balanced diet treatment groups: FO, RS, RS/FO, and control. Each group was meal fed for a 2 week restricted feeding period followed by an 8 week free feeding rebound period. Analysis was a 2x2 factorial with significance at p&lt;0.05. The FO showed significantly higher food intake, body weight, and retroperitoneal fat pad weight. Menhaden oil is low in DHA and EPA, which may be necessary for FO to be effective at reducing body fat. RS and RS/FO had larger ceca and lower pH levels in cecal contents indicating increased fermentation. RS/FO had the greatest cecal weight and lowest pH indicating a synergistic interaction between RS and FO which enhanced fermentation to higher levels within the large intestine than RS alone. This combination may benefit the health of the colon. Supported by the LSU AgCenter.

Interaction of Fenofibrate and Fish Oil in Relation to Lipid Metabolism in Mice

The aim of our study is to elucidate the interactive effects on lipid metabolism of fenofibrate and two fish oils with EPA and DHA contents in mice. Female C57BL/6J mice were fed purified experimental diets containing safflower oil (SO), EPA-rich menhaden oil (MO) or DHA-rich tuna oil (TO) with or without 0.1% fenofibrate for 8 weeks. At the end of the experiments, we measured plasma lipids and hepatic triglycerides and cholesterol, and the hepatic mRNA expression of lipogenic and lipidolytic genes. Plasma TG levels fell in the group fed MO or TO alone and fell significantly in all fenofibrate-treated groups. Although plasma total cholesterol levels fell significantly in fish oil-fed groups, fenofibrate treatments increased significantly plasma total cholesterol levels in these fish oil groups, but not in the group fed SO alone; however, hepatic triglyceride and total cholesterol levels markedly decreased in MO-or TO-fed mice. In lipid synthesis, the hepatic mRNA level of SREBP-1c was not reduced in either fish oil group; however, Insig-1 mRNA decreased in MO and TO feeding groups by about half and FAS or SCD-1 mRNA decreased significantly in MO and TO feeding groups, compared with the SO feeding group. In both fish oil groups, SREBP-2 mRNA decreased significantly and HMG-CoA reductase mRNA also decreased with/without fenofibrate. On the other hand, fenofibrate supplementation significantly induced the mRNA expression of AOX and UCP-2, which play a role in lipid catabolism, in all diets. CYP7A1 mRNA increased markedly in mice fed MO diet with fenofibrate, compared with TO diet with fenofibrate. These data suggest that differences in dietary contents of EPA and DHA do not influence the inhibition of lipogenesis, and that fenofibrate supplementation stimulates fatty acid oxidation, regardless of the oil type; however, cholesterol catabolism was induced by a combination of EPA-rich fish oil and fenofibrate, which suggests that EPA has a greater synergistic ability for cholesterol catabolism induction by fenofibrate than DHA.

Docosahexaenoic Acid (DHA), a Primary Tumor Suppressive Omega-3 Fatty Acid, Inhibits Growth of Colorectal Cancer Independent of p53 Mutational Status

Human colon carcinoma COLO 205, carrying wild type p53, grown subcutaneously in athymic mice was inhibited 80% by a high fat menhaden oil diet containing a mixture of omega-3 fatty acids compared to the low fat corn oil diet containing omega-6 fatty acids. Feeding a high fat diet of golden algae oil containing docosahexaenoic acid (DHA) as the sole long chain omega-3 fatty acid resulted in 93% growth inhibition. Similar findings were previously reported for WiDr colon carcinoma containing mutated p53 (His237). In vitro, 125 μM DHA inhibited COLO 205 growth by 81%, WiDr by 42%, while eicosapentaenoic acid (EPA) marginally inhibited growth of both lines by approximately 30%. DHA inhibited cell proliferation by 41% in WiDr but did not significantly inhibit proliferation in COLO 205. Cell cycle analysis revealed that DHA arrested cell cycle at Resting/Gap 1 (G0/G1 phase) in WiDr and at Gap 2/Mitosis (G2/M) phase in COLO 205. DHA induced apoptosis in COLO 205 but not in WiDr, and EPA did not induce apoptosis in either line. Taken together, these findings suggest DHA is the primary tumor suppressive ω-3 fatty acid in vivo and in vitro and inhibits cancer growth by p53 dependent and independent pathways, while the marginal inhibition by EPA is p53 independent.

Feeding Channel Catfish, Ictalurus punctatus, Diets Amended with Refined Marine Fish Oil Elevates Omega‐3 Highly Unsaturated Fatty Acids in Fillets

Abstract Channel catfish, Ictalurus punctatus, 88.4 ± 2.6 g/fish, were fed a basal diet amended with 4% of three processed menhaden, Brevoortia tyrannus, oils. These were compared with basal diets amended with 4% corn oil or 4% canola oil. Three replicate aquaria of nine fish each were fed assigned diets twice daily. At 6 wk, fish were group weighed, fillets were collected for sensory evaluation, fatty acid analysis by gas chromatography (GC). In a second study, catfish, 118.8 ± 3.2 g/fish, were stocked into fifteen 0.04‐ha earthen ponds and fed once daily for 16 wk one of four diets containing 2 or 4% of either catfish offal oil or refined (RF) menhaden oil. At harvest, fillets were saved for sensory evaluation and fatty acid analysis. Results showed no significant (P &gt; 0.05) differences among treatments for aquarium study and pond study variables such as weight gain, fillet proximate analysis, or pond production. GC analysis showed that levels of omega‐3 (n‐3) highly unsaturated fatty acids (HUFA) in fillet lipid were significantly (P &lt; 0.05) elevated for fish fed menhaden oil diets. Sensory evaluation revealed that fillets from fish fed RF menhaden oil had satisfactory flavor and could be a source of n‐3 HUFA for humans.

Modification of fillet composition and evidence of differential fatty acid turnover in sunshine bass Morone chrysops × M. saxatilis following change in dietary lipid source

Marine oil-based finishing diets have been used to restore fillet FA profile in several "medium-fat" fleshed aquaculture species, and a simple dilution model describing FA turnover has been established to predict and tailor final fillet composition. We evaluated finishing diet efficacy and suitability of the dilution model to describe patterns of FA change in a lean-fleshed model, sunshine bass. Two practical diets (45% crude protein, 15% crude lipid) were formulated, respectively containing corn oil (CO) or menhaden oil (MO) as the primary lipid sources. Sunshine bass (age 1 [approximately 14 mo], 347 +/- 8.6 g, mean individual weight +/- SEM) were stocked in a recirculating system and fed the diets according to different feeding regimens during the final 28 wk of the production cycle. Control groups were fed the CO or the MO feeds exclusively; whereas, the remaining treatment groups were transitioned from the CO diet to the MO diet at 4-, 8-, or 12-wk intervals. Upon completion of the feeding trial, fish were harvested, and production performance and fillet composition were assessed. Replacing MO with CO as the primary lipid source in sunshine bass diets yielded fillets with distinctly different FA profiles; however, finishing with a MO-based diet offered significant compensation for CO-associated reductions in fillet long-chain highly unsaturated FA (LC-HUFA). Although complete restoration was not observed, we achieved significant augmentation of endogenous n-3 FA within 4 wk of feeding the MO diet, and observed a significant increase in LC-HUFA and a beneficial shift in n-3:n-6 FA ratio after 8 weeks. Simple dilution accurately predicted tissue composition for most FA; however, deviations from the model were noted, suggesting selective retention of n-3, PUFA, and LC-HUFA and preferential catabolism of saturates. We conclude marine oil-based finishing diets can rapidly augment beneficial FA levels in sunshine bass fillets; however, simple dilution models do not fully describe selective FA metabolism observed for this lean-fleshed fish.

Dietary olive oil and menhaden oil mitigate induction of lipogenesis in hyperinsulinemic corpulent JCR:LA-cp rats: microarray analysis of lipid-related gene expression.

In the corpulent James C. Russell corpulent (JCR:LA-cp) rat, hyperinsulinemia leads to induction of lipogenic enzymes via enhanced expression of sterol-regulatory-binding protein (SREBP)-1c. This results in increased hepatic lipid production and hypertriglyceridemia. Information regarding down-regulation of SREBP-1c and lipogenic enzymes by dietary fatty acids in this model is limited. We therefore assessed de novo hepatic lipogenesis and hepatic and plasma lipids in corpulent JCR rats fed diets enriched in olive oil or menhaden oil. Using microarray and Northern analysis, we determined the effect of these diets on expression of mRNA for lipogenic enzymes and other proteins related to lipid metabolism. In corpulent JCR:LA-cp rats, both the olive oil and menhaden oil diets reduced expression of SREBP-1c, with concomitant reductions in hepatic triglyceride content, lipogenesis, and expression of enzymes related to lipid synthesis. Unexpectedly, expression of many peroxisomal proliferator-activated receptor-dependent enzymes mediating fatty acid oxidation was increased in livers of corpulent JCR rats. The menhaden oil diet further increased expression of these enzymes. Induction of SREBP-1c by insulin is dependent on liver x receptor (LXR)alpha. Although hepatic expression of mRNA for LXR itself was not increased in corpulent rats, expression of Cyp7a1, an LXR-responsive gene, was increased, suggesting increased LXR activity. Expression of mRNA encoding fatty acid translocase and ATP-binding cassette subfamily DALD member 3 was also increased in livers of corpulent JCR rats, indicating a potential role for these fatty acid transporters in the pathogenesis of disordered lipid metabolism in obesity. This study clearly demonstrates that substitution of dietary polyunsaturated fatty acid for carbohydrate in the corpulent JCR:LA-cp rat reduces de novo lipogenesis, at least in part, by reducing hepatic expression of SREBP-1c and that strategies directed toward reducing SREBP-1c expression in the liver may mitigate the adverse effects of hyperinsulinemia on hepatic lipid production.