The effects of hydrogenated coconut oil, safflower oil, and evening primrose oil on development of hypertension and sodium handling in spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) were fed a basal regular diet (BD) or three different fat-supplemented diets which contained 10% hydrogenated coconut oil (HCO), 10% safflower oil (SFO), or 10% evening primrose oil (EPO). The rats received these four different diets from 4 weeks to over 24 weeks of age. The development of hypertension in SHR was significantly retarded in the EPO-supplemented animals. The blood pressure was lower in the SFO group animals as compared with the BD and HCO groups, but this did not reach significance. Sodium excretion rate in young SHR was increased in the EPO group compared with the HCO and SFO groups, and the urinary K/Na ratio was decreased in the EPO group compared with the HCO and EPO groups. Water intake and urine volume were increased in the SFO group as compared with the HCO and EPO groups. Sodium concentration in erythrocytes was decreased in the rats receiving SFO. Pressor responses to norepinephrine and angiotensin II were enhanced in the EPO and SFO groups as compared with the basal chow group. These data suggest that a dietary supplementation of EPO which contains a substantial amount of gamma-linolenic acid consistently lowers blood pressure in SHR. The mechanism is uncertain, but the effects on sodium handling may in part be responsible for the retardation of the development of hypertension. There was a difference between the EPO and the SFO groups in sodium--water handling, and to some extent in the blood pressure development in SHR.     

Effect of dietary fish oil, vitamin E, and probucol on renal injury in the rat

Dietary fish oil, vitamin E, and probucol have been considered in a variety of human and experimental models of kidney disease. Using subtotal nephrectomized cholesterol-fed rats as a model for progressive kidney disease, we examined the effect of 5% dietary fish oil, or a combination of 5% dietary fish oil with 500 IU vitamin E/kg diet or 1% probucol on renal injury. Three-month-old Sprague Dawley rats were fed a control diet (C group) or a cholesterol supplemented (2%) diet (Ch group) containing either fish oil (FO group) or fish oil plus vitamin E (FO+E group) or fish oil plus probucol (FO+P group). After 4 weeks of dietary treatment, the right kidney was electrocoagulated and the left kidney nephrectomized. After 8 weeks, 24-hour urine was collected before sacrifice. No effect of the dietary treatments was noted on serum creatinine, blood urea nitrogen, or proteinuria, except that proteinuria was highest in FO+P group. Rats receiving the cholesterol diets had higher serum low density lipoprotein (LDL) + very low density lipoprotein (VLDL) cholesterol (P < 0.05). In contrast, rats in the FO+P group had the lowest serum total cholesterol and LDL+VLDL cholesterol among all groups. The FO group had 26% lower kidney alpha-tocopherol concentrations than the C group. However, inclusion of vitamin E in the diet (FO+E group) increased the kidney alpha-tocopherol status to a level comparable to that in the C group, whereas inclusion of probucol in fish oil diet (FO+P group) did not improve the kidney alpha-tocopherol status. Rats fed the cholesterol diet had a 2.5-fold higher glomerular segmental sclerosis (GSS) score and 1.5-fold higher glomerular macrophage (GM) subpopulation than the C group. These effects of the cholesterol diet were ameliorated by a fish oil diet (FO group: GSS by 30%, GM by 24%). The inclusion of vitamin E in the fish oil diet (FO+E group) did not further improve the GSS score or GM subpopulation. However, inclusion of probucol in fish oil diet (FO+P group) lowered the GSS score by 73% and reduced GM subpopulation by 83% compared with the Ch group. These remarkable changes can be attributed to the powerful hypocholesterolemic activity of probucol. Our findings indicate that progression of glomerular sclerosis in the rat remnant kidney model of progressive kidney disease can be significantly modulated with fish oil treatment.     

Effect of n-6 and n-3 polyunsaturated fatty acids ingestion on rat liver membrane-associated enzymes and fluidity

The influences of diets having different fatty acid compositions on the fatty-acid content, desaturase activities, and membrane fluidity of rat liver microsomes have been analyzed. Weanling male rats (35–45 g) were fed a fat-free semisynthetic diet supplemented with 10% (by weight) marine fish oil (FO, 12.7% docosahexaenoic acid and 13.8% eicosapentaenoic acid), evening primrose oil (EPO, 7.8% γ-linolenic acid and 70.8% linoleic acid) or a mixture of 5% FO-5% EPO. After 12 weeks on the respective diets, animals fed higher proportions of (n-3) polyunsaturated fatty acids (FO group) consistently contained higher levels of 20:3(n-6), 20:5(n-3), 22:5(n-3), and 22:6(n-3), and lower levels of 18:2(n-6) and 20:4(n-6), than those of the EPO (a rich source of (n-6) polyunsaturated fatty acids) or the FO + EPO groups. Membrane fluidity, as estimated by the reciprocal of the order parameter S_DPH, was higher in the FO than in the EPO or the FO + EPO groups, and the n-6 fatty-acid desaturation system was markedly affected.     

Effects of dietary fish oil supplementation on cellular adhesion molecule expression and tissue myeloperoxidase activity in hypercholesterolemic mice with sepsis

This study investigated the effects of fish oil on adhesion molecule expression and tissue myeloperoxidase (MPO) activity in hypercholesterolemic mice with sepsis. There were one control and two experimental groups in this study. The control group (C) was fed a regular chow diet for 7 weeks, while hypercholesterolemia in the experimental group was induced by feeding a high-fat diet (20%, w/w) with cholesterol (2%, w/w) for 4 weeks. Then the experimental group was divided into two subgroups with identical nutrient distributions except that one subgroup was fed soybean oil (SO), while part of the soybean oil was replaced by fish oil (FO) in the other one for 3 weeks. After feeding the diets for 7 weeks, sepsis was induced in all three groups by cecal and ligation and puncture (CLP), and mice were sacrificed at 0, 6 or 24 h after CLP, respectively. The results showed that the FO group had a higher intracellular interferon-gamma/interleukin-4 ratio and lower tumor necrosis factor-alpha and monocyte chemoattractant protein-1 concentrations in peritoneal lavage fluid at 6 h after CLP than those in the C and SO groups. Lymphocyte CD11a/CD18 expressions were higher at 0 and 6 h and neutrophil CD11b/CD18 were higher at 6 h in the SO group than in the FO and C groups. The SO group had higher plasma intercellular adhesion molecule (ICAM)-1 levels than C group at 0 and 6 h, whereas no difference in ICAM-1 concentrations were observed between the C and FO groups at 0 h after CLP. Hypercholesterolemia resulted in higher tissue MPO activities. There were no differences in MPO activities in various organs between the two experimental groups. These results suggest that hypercholesterolemic mice fed FO did not exhibit immunosuppression when complicated with sepsis. FO administration reduced adhesion molecule expressions and inflammatory-related mediators at the site of injury at an early but not a late stage of sepsis. However, compared with the SO group, the influences of FO on MPO activities in various organs were not obvious in hypercholesterolemic mice with sepsis.     

The influence of fish oil supplementation on plasma lipoproteins and arterial lipids in vervet monkeys with established atherosclerosis.

There is controversy about whether supplementing diets with marine fish oil can regress, promote or prevent atherosclerosis. Therefore the effects of an Atlantic pilchard oil (FO) supplement and dietary change were measured in a proven atherosclerosis model. Vervet or African Green monkeys were fed an atherogenic diet (AD) for long enough to ensure progression before treatments started. Matched groups were then treated for 20 months, either by adding FO to the AD (AD/FO), or by changing to a therapeutic diet with FO (TD/FO). Control treatments consisted of supplementing with sunflower oil (SO) instead of FO, so that treatments were AD/SO and TD/SO. The same total polyunsaturates were supplied by the FO and SO and the dose of FO was realistic (2.5% of total energy). A reference group (R) received the TD with no oil supplements. Supplementing with FO did not change the concentrations of total, low or high density lipoprotein cholesterol in plasma. After The AD/FO the intimas of aortas contained more total (p < or = 0.001), free (p < or = 0.05) and esterified (p < or = 0.05) cholesterol, total phospholipid (p < or = 0.01) and sphingomyelin (p < or = 0.05) than after the AD/SO. After FO supplementation eicosapentaenoic acid was significantly higher and arachidonic acid significantly lower in the plasma and aorta intima phosphatidylcholine. None of these changes was anti-atherogenic in terms of atherosclerosis measured in the same individuals (1). Nor did FO increase the efficacy of the TD.     

Effects of dietary fish oil on thyroid hormone signaling in the liver

n?3 polyunsaturated fatty acids (PUFAs) present in fish oil (FO) potently decrease serum lipids, which is also an effect of thyroid hormones. Both PUFAs and thyroid hormones affect hepatic lipid metabolism, and here we hypothesized that a long-term diet rich in n?3 PUFAs would enhance thyroid hormone action in the liver. Female rats received isocaloric and normolipid diets containing either soybean oil (SO) or FO during lactation. Male offspring received the same diet as their dams since weaning until sacrifice when they were 11 weeks old. FO group, as compared to SO group, exhibited lower body weight since 5 weeks of age until sacrifice, with no alterations in food ingestion, lower retroperitoneal white fat mass and elevated inguinal fat mass relative to body weight, with unchanged water and lipid but reduced protein percentage in their carcasses. FO diet resulted in lower serum triglycerides and cholesterol. Serum total triiodothyronine, total thyroxine and thyrotropin were similar between groups. However, liver thyroid hormone receptor (TR) β1 protein expression was higher in the FO group and correlated negatively with serum lipids. Liver 5′-deiodinase activity, which converts thyroxine into triiodothyronine, was similar between groups. However, the activity of hepatic mitochondrial glycerophosphate dehydrogenase, the enzyme involved in thermogenesis and a well-characterized target stimulated by T3 via TRβ1, was higher in the FO group, suggesting enhancement of thyroid hormone action. These findings suggest that the increase in thyroid hormone signaling pathways in the liver may be one of the mechanisms by which n?3 PUFAs exert part of their effects on lipid metabolism.     

Effect of dietary fish oil on tumor-induced hyperlipidemia and tumor growth in rats implanted with a methylcholanthrene-induced sarcoma

Male Fischer 344 rats implanted with a methylcholanthrene-induced sarcoma (MCS), along with normal (or control) animals, were fed diets containing either 10% com oil (CO) or 2% CO + 8% fish oil (FO), designated as diets CO and FO, respectively, in a study designed to determine the effect of dietary FO on serum lipids (in the presence or absence of a tumor) and the growth and fatty acid composition of the MCS. For both diets, MCS-bearing rats had significantly (p < 0.05) higher serum levels of triglycerides, cholesterol, phospholipids, and total lipids than controls. For both controls and tumor-bearers, serum levels of all these lipids were, with the exception of cholesterol for the tumorbearers, significantly lower in rats receiving the FO diet than for the corresponding groups receiving the CO diet. Relative to rats fed the CO diet, those fed the FO diet had significantly higher serum levels of some fatty acids (e.g., 20:5n-3) but significantly lower levels of others (e.g., 18:2n-6), regardless of tumor status. For the tumor-bearers, differences in the levels of fatty acids in MCS tissue reflected differences in the fatty acid composition of total serum lipids. Sarcoma growth was unaffected by diet. Thus, feeding dietary FO resulted in changes in the lipid status of both control and tumor-bearing rats. Since sarcoma growth was unaffected by diet, the reduction in the severity of MCS-induced hyperlipidemia by FO appears to be due to an effect of the oil per se.     

Docosahexaenoic acid is an antihypertensive nutrient that affects aldosterone production in SHR.

The effects of dietary docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, on blood pressure and some pressure-regulating systems were measured in young spontaneously hypertensive rats (SHR). Plasma aldosterone and corticosterone levels, adrenal aldosterone production in vitro, and characteristics of adrenal angiotensin receptors were measured after 6 weeks of diet. Renal cytochrome P450 (CYP) 4A gene expression and arachidonic acid metabolism by renal microsomes were also investigated. Plasma cholesterol, triglycerides, and high-density lipoprotein cholesterol were measured. Diets contained either corn/soybean oil alone (CSO), or oil enriched with DHA. After 6 weeks, rats fed DHA had systolic blood pressures averaging 34 mmHg less than controls (P < 0.001). Plasma aldosterone levels were 33% lower in the DHA-fed animals than in controls (22 +/- 3 vs. 33 +/- 3.7 ng/dl, P < 0.05). Plasma levels of corticosterone were 18% lower in animals fed DHA than in controls, but this difference was not statistically significant. Adrenal glomerulosa cells from DHA-fed rats produced less aldosterone in vitro in response to angiotensin II, ACTH, or potassium. The difference was less marked when aldosterone production was stimulated by supplying exogenous corticosterone, suggesting an effect of DHA on postreceptor steps in signal transduction or the early pathway of aldosteronogenesis. We found no significant differences in angiotensin receptor subtype, number, or affinity. Production of arachidonic epoxides by renal microsomes was 17% lower in DHA-fed animals than in controls (P < 0.05). Renal cortical mRNA levels of CYP4A genes and formation of 19- and 20-hydroxyeicosatetraenoic acid (HETE) did not differ between dietary groups. Plasma total cholesterol and high-density-lipoprotein (HDL) levels were significantly reduced in SHR fed the DHA supplement, but triglyceride levels were not significantly different. The effects of DHA on steroid and eicosanoid metabolism may be part of the mechanism by which this fatty acid prevents some of the hypertension in growing SHR.     

Fish oil prevents excessive hepatic lipid accumulation without inducing oxidative stress

We examined the effects of fish oil (FO) on high-cholesterol diet-induced hepatic lipid accumulation and oxidative stress. Female C57BL/6J mice were fed diets consisting of safflower oil (SO), 1 en% FO (1FO), 2 en% FO (2FO), or 20 en% FO (20FO) with or without 2 weight% (wt%) cholesterol (SO/CH, 1FO/CH, 2FO/CH, and 20FO/CH groups, respectively) for 8 weeks. The hepatic triacylglyceride levels were significantly lower in the 2FO/CH and 20FO/CH groups than in the SO/CH group. The hepatic mRNAs of fatty acid oxidation-related genes were upregulated and the fatty acid synthesis-related genes were downregulated by the FO feeding. Adverse effects were not observed in the plasma levels of indicators of oxidative stress in response to the consumption of FO up to 20 en%. These results suggest that FO consumption in the range of 2–20 en% prevents hepatic lipid accumulation, thus improving lipid metabolism without causing oxidative stress.     

Super,Red Palm and Palm Oleins Improve the Blood Pressure,Heart Size,Aortic Media Thickness and Lipid Profile in Spontaneously Hypertensive Rats

Background

Oleic acid has been shown to lower high blood pressure and provide cardiovascular protection. Curiosity arises as to whether super olein (SO), red palm olein (RPO) and palm olein (PO), which have high oleic acid content, are able to prevent the development of hypertension.

Methodology/Principal Findings

Four-week-old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were fed 15% SO, RPO or PO supplemented diet for 15 weeks. After 15 weeks of treatment, the systolic blood pressure (SBP) of SHR treated with SO, RPO and PO were 158.4±5.0 mmHg (p<0.001), 178.9±2.7 mmHg (p<0.001) and 167.7±2.1 mmHg (p<0.001), respectively, compared with SHR controls (220.9±1.5 mmHg). Bradycardia was observed with SO and PO. In contrast, the SBP and heart rate of treated WKY rats were not different from those of WKY controls. The SO and PO significantly reduced the increased heart size and thoracic aortic media thickness observed in untreated SHR but RPO reduced only the latter. No such differences, however, were observed between the treated and untreated WKY rats. Oil Red O enface staining of thoracic-abdominal aorta did not show any lipid deposition in all treated rats. The SO and RPO significantly raised serum alkaline phosphatase levels in the SHR while body weight and renal biochemical indices were unaltered in both strains. Serum lipid profiles of treated SHR and WKY rats were unchanged, with the exception of a significant reduction in LDL-C level and total cholesterol/HDL ratio (atherogenic index) in SO and RPO treated SHR compared with untreated SHR.

Conclusion

The SO, RPO and PO attenuate the rise in blood pressure in SHR, accompanied by bradycardia and heart size reduction with SO and PO, and aortic media thickness reduction with SO, RPO and PO. The SO and RPO are antiatherogenic in nature by improving blood lipid profiles in SHR.     

蚕蛹基础日粮中添加不同脂肪源对框鳞镜鲤生长、体成分及健康状况的影响

将324尾健康框鳞镜鲤Cyprinus carpio var. specularis (10.700.70) g随机平均分配在室内循环水养殖系统的12个养殖缸里。在蚕蛹基础饲料中分别添加2%的大豆油(SO)、菜籽油(RO)、鱼油(FO)及混合油(MIX, 大豆油:菜籽油:鱼油=1:1:1), 配制4组等氮(36.5%)等脂(7.0%)饲料, 饲养58d后, 探讨框鳞镜鲤对不同脂肪源的利用效果。结果表明:(1)大豆油组终末体重显著大于混和油组, 肠长比显著大于其他各组, 肥满度和肠指数显著大于鱼油组(P0.05); 肝胰脏指数混合油组显著低于鱼油组和大豆油组, 菜籽油组显著低于大豆油组(P0.05); (2)全鱼水分大豆油组显著高于菜籽油组和混合油组, 粗脂肪含量显著低于其他各组(P0.05); 肌肉水分大豆油组显著大于鱼油组和混合油组(P0.05); 不同脂肪源对框鲤全鱼和肌肉的粗蛋白和灰分、肌肉粗脂肪、肝胰脏的一般体成分无显著影响(P0.05); (3)肝胰脏和肌肉脂肪酸组成基本反映了饲料的脂肪酸组成; 肝胰脏PUFA水平大豆油和菜籽油组相近, 均显著高于鱼油组(P0.05); 肌肉PUFA水平大豆油组显著高于鱼油组(P0.05), 肌肉HUFA水平菜籽油组显著高于鱼油组和混合油组(P0.05); (4)除菜籽油组血清GLU水平显著高于大豆油组外(P0.05), 4种脂肪源对框鲤其他血清生化指标水平没有显著影响(P0.05); (5)组间血清T-SOD活性没有显著差异(P0.05), 大豆油组GSH-XP活性显著大于其他各组(P0.05), MDA水平显著低于鱼油组及混合油组(P0.05), 鱼油组血清AKP活性显著低于其他各组(P0.05); 鱼油组肝胰脏T-SOD活性显著高于其他各组(P0.05), AKP活性显著高于菜籽油组和混合油(P0.05), GSH-XP活性显著高于混合油组(P0.05), MDA水平各组无显著差异(P0.05)。综上所述, 框鳞镜鲤对大豆油的利用效果最好, 其次是菜籽油、鱼油和混合油利用效果较差。       

Effects of Various Polyunsaturated Fatty Acids on Blood Cholesterol and Eicosanoids in Rats

The hypocholesterolemic efficacy of various polyunsaturated fatty acids was compared in rats given cholesterol-enriched diets with (0.004%) or without indomethacin, the cyclooxygenase inhibitor. Evening primrose oil (EPO, linoleic+ γ-linolenic), safflower oil (SFO, linoleic) or soybean oil (SBO, linoleic + α-linolenic) were added to diets at the 10% level. The serum cholesterol level of the EPO group was consistently lower than the other groups and after 3 weeks, it was significantly different from the SFO group without indomethacin and the SBO group with indomethacin. In rats fed EPO, the aorta tended to produce more prostacyclin whereas the concentration of plasma thromboxane B₂ was much lower than in rats fed SFO or SBO. The effects of indomethacin on these eicosanoids were less evident in rats fed EPO. Thus, in addition to the hypocholesterolemic action of β-linolenic acid (GLA) in preference to linoleic and possibly α-linolenic acid, GLA appears to cultivate an environment suitable for the prevention of carbiovascular disease even in the presence of excess cholesterol in the diet.     

Fish oil and indomethacin in combination potently reduce dyslipidemia and hepatic steatosis in LDLR -/- mice

Fish oil (FO) is a potent anti-inflammatory and lipid-lowering agent. Because inflammation can modulate lipid metabolism and vice versa, we hypothesized that combining FO with cyclooxygenase inhibitors (COXIBs), well-known anti-inflammatory drugs, can enhance the anti-inflammatory and lipid-lowering effect of FO. LDLR (-/-) mice were fed a high-fat diet supplemented with 6% olive oil or FO for 12 wk in the presence or absence of indomethacin (Indo, 6 mg/l drinking water). FO reduced plasma total cholesterol by 30% but, in combination with Indo, exerted a greater decrease (44%). The reduction of liver cholesterol ester (CE) and triglycerides (TG) by FO (63% and 41%, respectively) was enhanced by Indo (80% in CE and 64% in TG). FO + Indo greatly increased the expression of genes modulating lipid metabolism and reduced the expression of inflammatory genes compared with control. The mRNA and/or protein expression of pregnane X receptor (PXR) and cytochrome P450 isoforms that alter inflammation and/or lipid metabolism are increased to a greater extent in mice that received FO + Indo. Moroever, the nuclear level of PXR is significantly increased in FO + Indo group. Combining FO with COXIBs may exert their beneficial effects on inflammation and lipid metabolism via PXR and cytochrome P450.     

不同脂肪源对泥鳅稚鱼生长性能及脂肪酸组成的影响

为研究饲料不同脂肪源对泥鳅稚鱼生长性能及鱼体脂肪酸组成的影响, 实验选择初始体重为(10.002.00) mg的健康泥鳅稚鱼1500尾, 随机分为5组, 每组3个重复, 每个水箱100尾鱼, 分别投喂5种含有鱼油(FO)、大豆油(SO)、玉米油(CO)、花生油(PeO)和棕榈油(PaO)的配合饲料, 每种饲料3个重复, 饲养期为40d。结果显示, 摄食不同脂肪源饲料的泥鳅稚鱼在增重率、成活率、饲料系数等生长性能指标和体成分上没有显著差异(P0.05), 但是, 摄食FO组鱼体极性脂肪含量显著高于其他植物油组(P0.05)。鱼油组鱼体中性和极性脂肪中总n-3系脂肪酸含量和EPA+DHA含量显著高于其他植物油组(P0.05)。植物油组鱼体极性脂肪中20:4n-6含量显著高于鱼油组(P0.05), 表明泥鳅稚鱼具有将C18转换为C20的能力。研究表明, 在饲料中添加足量磷脂, 鱼油、大豆油、玉米油、花生油、棕榈油都可以用作泥鳅稚鱼期专用饲料脂肪源。     

Dietary fats affect macrophage-mediated cytotoxicity towards tumour cells

In the present study, the effects of feeding mice diets of different fatty acid compositions on the production of TNF-alpha and nitric oxide by lipopolysaccharide-stimulated peritoneal macrophages and on macrophage-mediated cytotoxicity towards L929 and P815 cells were investigated. C57Bl6 mice were fed on a low-fat (LF) diet or on high-fat diets (21% fat by weight), which included coconut oil (CO), olive oil (OO), safflower oil (SO) or fish oil (FO) as the principal fat source. The fatty acid composition of the macrophages was markedly influenced by that of the diet fed. Lipopolysaccharide (LPS)-stimulated macrophages from FO-fed mice showed significantly lower production (up to 80%) of PGE2 than those from mice fed on each of the other diets. There was a significant positive linear correlation between the proportion of arachidonic acid in macrophage lipids and the ability of macrophages, to produce PGE2. Lipopolysaccharide-stimulated TNF-alpha production by macrophages decreased with increasing unsaturated fatty acid content of the diet (i.e. FO < SO < OO < CO < LF). Macrophages from FO-fed mice showed significantly lower production of TNF-alpha than those from mice fed on each of the other diets. Nitrite production was highest for LPS-stimulated macrophages from mice fed on the LF diet. Macrophages from FO-fed mice showed significantly higher production of nitrite than those from mice fed on the OO and SO diets. Compared with feeding the LF diet, feeding the CO, OO or SO diets significantly decreased macrophage- mediated killing of P815 cells (killed by nitric oxide). Fish oil feeding did not alter killing of P815 cells by macrophages, compared with feeding the LF diet; killing of P815 cells was greater after FO feeding than after feeding the other high fat diets. Compared with feeding the LF diet, feeding the OO or SO diets significantly decreased macrophage-mediated killing of L929 cells (killed by TNF). Coconut oil or FO feeding did not alter killing of L929 cells by macrophages, compared with feeding the LF diet. It is concluded that the type of fat in the diet affects macrophage composition and alters the ability of macrophages to produce cytotoxic and immunoregulatory mediators and to kill target tumour cells.     

Beneficial effects of alpha linolenic acid rich flaxseed oil on growth performance and hepatic cholesterol metabolism in high fat diet fed rats

The purpose of the study was to investigate the effect of flaxseed oil (FO), rich in alpha-linolenic acid (ALA) (18:3 n-3) on growth parameters and lipid metabolism of rats fed with high fat diet. High fat diet (HFD) resulted in significant alterations in hepatic lipids, increase in body weight gain and negative effect on lipoprotein metabolism. FO supplementation significantly lowered the increase in body weight gain, liver weight, plasma cholesterol, triglycerides, phospholipids, free fatty acids, high-density lipoprotein (HDL), low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein (VLDL), LDL/HDL and TC/HDL ratio in HFD fed rats. FO significantly reduced the hepatic and plasma lipid levels indicating its hypolipidemic activity. On the other hand, oral administration of FO exhibited lower plasma lipoprotein profile as compared to HFD rats. Hepatic protection by FO is further substantiated by the normal liver histological findings in HFD fed rats. These data suggest that FO participate in the normal regulation of plasma lipid concentration and cholesterol metabolism in liver. No adverse effect of FO on growth parameters and plasma lipids in rats fed with fat-free diet. The results of the present study demonstrate that FO may be developed as a useful therapy for hyperlipidemia through reducing hepatic lipids, thereby proving its hypolipidemic activity.     

Reversibility of the changes induced by n-3 fatty acids in mouse plasma, liver and blood cell lipids

The changes induced by dietary n-3 fatty acids (FA) in the lipids and FA of plasma, liver and blood cells, and their reversibility, was studied in mice given a diet containing 9% fish oil (FO) for 2 weeks and then returned to, and kept for another 2 weeks on, the usual standard lab chow diet. In plasma, the concentrations of phospholipids (PL), mostly phosphatidylcholine (PC), triacylglycerols (TG), cholesterol and cholesterol esters (CE) decreased rapidly after starting the FO diet, and remained low from day 3 onwards. This decrease was concomitant with a remarkable reduction in the n-6 FA, especially 18:2n-6, not compensated for by the relative enrichment in n-3 FA induced by FO. In liver, TG and CE decreased and PL slightly increased, all of them showing reduced n-6/n-3 ratios. Sphingomyelin, which lacks polyunsaturated FA other than small amounts of 18:2 and 24:2n-6, showed altered ratios between its very long chain monoenes and saturates. In the washout phase, the most rapid event was an immediate increase in 18:2n-6 and after a few days in 20:4n-6 in plasma and liver, where most of the lipid and FA changes were reversed completely in about 10 days. In the case of blood cells even 2 weeks were insufficient for a reversal to the initial n-6/n-3 ratios. The lipid class responsible for this lack of reversibility was phosphatidylethanolamine, PC having returned to the initial fatty acid composition during the stated period.     

Effects of dietary fat energy restriction and fish oil feeding on hepatic metabolic abnormalities and insulin resistance in KK mice with high-fat diet-induced obesity

We investigated the effects of dietary fat energy restriction and fish oil intake on glucose and lipid metabolism in female KK mice with high-fat (HF) diet-induced obesity. Mice were fed a lard/safflower oil (LSO50) diet consisting of 50 energy% (en%) lard/safflower oil as the fat source for 12 weeks. Then, the mice were fed various fat energy restriction (25 en% fat) diets — LSO, FO2.5, FO12.5 or FO25 — containing 0, 2.5, 12.5, or 25 en% fish oil, respectively, for 9 weeks. Conversion from a HF diet to each fat energy restriction diet significantly decreased final body weights and visceral and subcutaneous fat mass in all fat energy restriction groups, regardless of fish oil contents. Hepatic triglyceride and cholesterol levels markedly decreased in the FO12.5 and FO25 groups, but not in the LSO group. Although plasma insulin levels did not differ among groups, the blood glucose areas under the curve in the oral glucose tolerance test were significantly lower in the FO12.5 and FO25 groups. Real-time polymerase chain reaction analysis showed fatty acid synthase mRNA levels significantly decreased in the FO25 group, and stearoyl-CoA desaturase 1 mRNA levels markedly decreased in the FO12.5 and FO25 groups. These results demonstrate that body weight gains were suppressed by dietary fat energy restriction even in KK mice with HF diet-induced obesity. We also suggested that the combination of fat energy restriction and fish oil feeding decreased fat droplets and ameliorated hepatic hypertrophy and insulin resistance with suppression of de novo lipogenesis in these mice.     

Echium oil reduces plasma lipids and hepatic lipogenic gene expression in apoB100-only LDL receptor knockout mice

We tested the hypothesis that dietary supplementation with echium oil (EO), which is enriched in stearidonic acid (SDA; 18:4 n-3), the product of Delta-6 desaturation of 18:3 n-3, will decrease plasma triglyceride (TG) concentrations and result in conversion of SDA to eicosapentaenoic acid (EPA) in the liver. Mildly hypertriglyceridemic mice (apoB100-only LDLrKO) were fed a basal diet containing 10% calories as palm oil (PO) and 0.2% cholesterol for 4 weeks, after which they were randomly assigned to experimental diets consisting of the basal diet plus supplementation of 10% of calories as PO, EO or fish oil (FO) for 8 weeks. The EO and FO experimental diets decreased plasma TG and VLDL lipid concentration, and hepatic TG content compared to PO, and there was a significant correlation between hepatic TG content and plasma TG concentration among diet groups. EO fed mice had plasma and liver lipid EPA enrichment that was greater than PO-fed mice but less than FO-fed mice. Down-regulation of several genes involved in hepatic TG biosynthesis was similar for mice fed EO and FO and significantly lower compared to those fed PO. In conclusion, EO may provide a botanical alternative to FO for reduction of plasma TG concentrations.