FO Feeding Research Articles

Decreased secretion of very-low-density lipoprotein triacylglycerol and apolipoprotein B is associated with decreased intracellular triacylglycerol lipolysis in hepatocytes derived from rats fed orotic acid or n-3 fatty acids.

Hepatocytes from rats fed a chow (control) diet or from rats fed a chow diet supplemented with either orotic acid (OA; 1%, w/w) or fish oil (FO; 20%, v/w) were maintained in culture for periods up to 48 h. during the first 24 h period, the low rates of output of very-low-density lipoprotein (VLDL)-associated triacylglycerol (TAG) and apolipoprotein B (apoB) in hepatocytes from the FO- and OA-fed animals were associated with significantly lower rates of intracellular TAG lipolysis and re-esterification. Most of the VLDL TAG secreted was mobilized via lipolysis of the intracellular TAG pool, but the proportion of VLDL TAG secreted via this route in cells from the FO-fed and OA-fed animals was decreased compared with that in the control-fed animals' cells. In the presence of exogenous oleate the inhibitory effect of OA feeding on VLDL apoB and TAG secretion persisted in the derived hepatocytes for up to 48 h following isolation. However, when oleate was absent no inhibitory effect on the secretion of TAG and apoB was observed between 24 and 48 h. Under these conditions the rate of intracellular TAG turnover returned to normal. The initial inhibitory effect of FO feeding on VLDL TAG and apoB secretion did not persist in the derived hepatocytes between 24 h and 48 h of culture in the presence of exogenous oleate. Although intracellular TAG lipolysis and VLDL TAG and apoB secretion rates appear to be positively correlated, a causal relationship has not been conclusively established.

Changes in fatty acid metabolism in rat hepatocytes in response to dietary n-3 fatty acids are associated with changes in the intracellular metabolism and secretion of apolipoprotein B-48

Cultured hepatocytes from rats fed a low fat, chow diet (LF) or diets rich in fish oil (FO, 20% v/w) or olive oil (OO, 20%, v/w) were used to determine how the intracellular metabolism and secretion of apolipoproteins (apo)B-100 and B-48 respond to in vivo and in vitro manipulations of fatty acid esterification, storage, secretion, and oxidation. Hepatocytes from the FO- and OO-fed rats had higher initial triacylglycerol (TAG) contents and higher rates of fatty acid oxidation and ketogenesis than hepatocytes from the LF-fed group. However, only in the cells from the FO-fed animals was there any decrease in the rate of TAG synthesis and in the secretion of VLDL TAG. Decreased secretion of TAG by the FO hepatocytes was accompanied by a decreased synthesis and degradation of apoB, particularly apoB-48, and a decreased secretion of apoB-48 VLDL. In all dietary groups a substantial proportion of the apoB-48 and apoB-100 secreted into the medium was associated with small, lipid-poor particles of density > 1.006. FO feeding had no effect on the amounts of apoB-48 and apoB-100 that appeared in this fraction. Dietary composition affected the channelling of exogenous oleate in the culture medium into the oxidative and esterification pathways. While exogenous fatty acid increased the secretion of VLDL TAG in the FO-fed group, VLDL TAG secretion remained lower than that observed in the hepatocytes from the LF- and OO-fed groups cultured under identical conditions. Exogenous oleate did not significantly increase the secretion of either newly-synthesized apoB-48 or apoB-100 by hepatocytes in either of the dietary groups. We conclude that, in rat liver, a decreased capacity to transport TAG out of the hepatocyte after consumption of a diet rich in fish oil is associated with a decreased synthesis and presecretory degradation of apoB-48, and with a decreased secretion of VLDL apoB-48.

Effect of Dietary α-Linolenic Acid on Growth, Metastasis, Fatty Acid Profile and Prostaglandin Production of Two Murine Mammary Adenocarcinomas

The purpose of this study was to determine whether dietary (n-3) fatty acids would affect mammary tumor growth and metastasis. Weanling female BALB/c mice were fed diets that contained 10% corn oil (CO), linseed oil (LO) or a fish oil-corn oil mix (FO) for 3-8 wk prior to receiving subcutaneous injections of one of two syngeneic mammary tumor cell types (410 and 410.4). Tumor growth was assessed by monitoring mean tumor diameter and tumor weight upon removal. Feeding LO, but not FO, reduced the growth (p less than 0.05) of 410.4 mammary tumors compared with growth in those fed CO. Metastasis data paralleled the tumor growth rate. Feeding LO and FO enhanced (p less than 0.005) incorporation of (n-3) fatty acids into tumors. Tumor prostaglandin E (PGE) production was reduced (p less than 0.005) by LO and FO, compared with CO. FO feeding reduced 410.4 tumor PGE synthesis more (p less than 0.05) than LO feeding, yet tumor growth was only inhibited by LO. These data suggest an inhibitory effect of dietary linolenic acid [i.e., 18:3 (n-3)] on mammary tumor growth and metastasis. However, this effect did not directly correlate with diet-induced changes in PGE synthesis.

High Linoleic Acid Diets Ameliorate Diabetic Nephropathy in Rats

The value of high polyunsaturated fatty acid (PUFA) diets in preventing diabetic nephropathy in rats was studied. Diabetes was induced by intravenous injection of streptozotocin (SZ), 65 mg/kg. Rats were divided in four groups fed diets containing 11% fat for 38 weeks. Dietary fat derived from four sources: beef tallow (BT; rich in saturated fatty acids), evening primrose oil (EPO; rich in gamma linolenic [GLA] and linoleic acids [LA]), safflower oil (SO; rich in LA), and fish oil (FO; rich in eicosapentaenoic [EPA] and docosahexaenoic [DHA] acids). Ultralente insulin was administered every other day to maintain the blood glucose levels between 11.1 and 22.2 mmol/L (200 and 400 mg/dL). The diets prepared with EPO and SO had a clear beneficial effect on proteinuria, glomerular sclerosis, and tubular abnormalities, as compared with BT. Both diets also increased the ratio of renal cortical production of 6-keto-PGF1 alpha to thromboxane B2 (TXB2), the stable metabolites of PGI2 and TXA2, respectively. They did not induce significant changes in plasma lipid composition. The FO diet did not have an effect on renal disease, but decreased plasma lipids and inhibited eicosanoid synthesis by platelets and kidney cortex. FO feeding was associated with a lowered 6-keto-PGF1 alpha/TXB2 ratio. It is concluded that high LA diets are protective in this model of diabetic nephropathy. The effect may be secondary to modifications of the eicosanoid balance. Diets containing FO have a beneficial effect on plasma lipids in this model.

IMPROVED SURVIVAL OF HETEROTOPIC CARDIAC ALLOGRAFTS IN RATS WITH DIETARY n-3 POLYUNSATURATED FATTY ACIDS

A heterotopic cardiac transplant model, with male Fischer 344 rats as donors and Long Evans rats as recipients, was utilized to investigate the effect of dietary n-3 polyunsaturated fatty acids on acute rejection. Both donor and recipient rats were fed purified diets high in either n-3 polyunsaturated fatty acids (from concentrated n-3 ethyl esters [EE] or fish oil [FO]) or n-6 polyunsaturated fatty acids (from corn oil [CO]) for either 2-3 or 3-4 weeks before transplant. The recipient rats continued on their diets until rejection. The AIN-76A-based diets (with 30% of calories as fat) had adequate essential fatty acids and were balanced for sterols and antioxidants. Allograft survival was significantly increased by 45% when recipient rats were fed EE as compared to the control (CO diet fed to both donor and recipient), regardless of the diet fed to the donor. There was a slight but significant increase in allograft survival when only donor rats were fed the EE diet 2-3 weeks before transplant. With the FO diet (containing one third of the n-3 fatty acids in the EE diet), only the group fed FO to both donor and recipient (starting 2-3 weeks before transplant) showed a significant increase in allograft survival over the control. However, if the FO diets were fed for 3-4 weeks before transplant, increased survival was seen in groups fed FO to either the donor or recipient alone. In this case, allograft survival with FO feeding to both donor and recipient was not different from recipient treatment alone. In all the studies there was a significant and direct correlation between allograft survival and the donor heart phospholipid n-3/n-6 fatty acid ratio and the n-3 fatty acid content (at rejection). There was an indirect relationship with the n-6 fatty acid content. There was no detectable 20:3 (n-9) in the cardiac phospholipids, indicating the absence of essential fatty acid deficiency. Recipient diets were the strongest determinant of the fatty acid composition in the transplanted donor heart. The data indicate that providing dietary n-3 polyunsaturated fatty acids before and after cardiac transplant to recipient animals provides a significant protection against acute rejection.

Susceptibility of RDM4 lymphoma cells to LAK-mediated lysis is decreased in tumor bearers fed fish oil high fat regimen

RDM4 lymphoma cells were grown intraperitoneally in genetically compatible AKR mice fed either regular mouse chow, or diet supplemented with either saturated fat (hydrogenated beef tallow = HBT) or unsaturated fat (fish oil = FO). It was observed that the lymphoma cells number was significantly greater in FO-fed hosts and lower in HBT-fed hosts, than in the mice fed regular chow. The tumor bearers diet did not dramatically influence the rate of DNA synthesis of RDM4 cells, as measured by [ 3H]thymidine uptake in culture, a few hours after harvesting from the peritoneal cavity. It was repeatedly found that FO feeding of the tumor bearers elicited an increased resistance of RDM4 cells to lysis by LAK effectors, as appraised in vitro by 51Cr release test and in vivo by the “Winn assay”. Different FO percentage of the diet (16%, 8%, 4%) resulted in comparable reduction of susceptibility of RDM4 cells to lysis by LAK effectors. Lipid analysis showed that RDM4 cells grown in mice fed FO diet or HBT diet differed markedly in their fatty acid composition and that their resistance to lysis by LAK cells correlated with the quantity of oxidizable fatty acids especially of the n-6 type.