Effect of dietary fat level and polyunsaturated fatty acid content on the phospholipid composition of rat cardiac mitochondrial membranes and mitochondrial ATPase activity

Weanling rats were fed either high fat diets containing 40% of calories as fat or low fat diets containing 15% of calories as fat for 14 days. All diets were formulated to contain equivalent essential nutrients per calorie content for the nonfat components. For both dietary fat levels, the polyunsaturated to saturated fatty acid (P/S) ratio was adjusted by substitution of beef tallow for soybean oil to provide a dietary P/S ratio of 2.0 or 0.25. After feeding, hearts were removed from six replicate groups of animals per diet treatment, and mitochondria were isolated. Phospholipids were extracted from the mitochondrial membranes, and cardiolipin, phosphatidylcholine and phosphatidylethanolamine content were quantitatively analyzed using an iatroscanner. In addition, fatty acyl tail composition of each purified phospholipid was determined. Mitochondrial ATPase was also assessed by ATP-32Pi exchange assay. Feeding high fat diets increased phosphatidylcholine content of the mitochondrial membrane. High fat diets resulted in a relative increase in mitochondrial cardiolipin content that was apparently unaffected by the P/S ratio of the diet fed. Both the fat level in the diet and the P/S content altered ATPase activity. This composition to those potentially consumed by humans can result in alterations in membrane structural constituents of cardiac mitochondria and have potential to alter lipid-dependent functions of integral membrane proteins.     

Influence of reduced food intake on polyunsaturated fatty acid metabolism in zinc-deficient rats

The influence of reduced food intake on metabolism of liver phospholipids (PL) in zinc-deficient (ZD) rats was measured. Wealing male Long-Evans rats were fed ad libitum zinc-deficient (2 micrograms Zn/g diet) and zinc-adequate (20 micrograms Zn/g diet) diets for 21 days. A pair-fed (PF) group was included. ZD and PF rats displayed significantly increased levels of linoleic (18:2 omega 6) and dihomo-gamma-linolenic acid (20:3 omega 6). Both ZD and PF rats displayed increased levels of gamma-linolenic acid (18:3 omega 6), but the increase was significant only in PF rats. ZD and PF rats displayed decreased levels of arachidonic acid (20:4 omega 6), but the decrease was significant only in PF rats. Both ZD and PF rats displayed significantly reduced levels of 22:5 omega 6. Both ZD and PF rats displayed increased products of delta 6 desaturation and decreased products of delta 5 and delta 4 desaturation. Significantly increased products of delta 9 desaturation were noted in both ZD and PF rats. ZD and PF rats displayed significant increases in C20 elongation products. ZD and PF rats displayed significantly decreased levels of omega 6 metabolites but not total omega 6 acids. ZD rats showed significantly increased levels of total omega 3 acids and omega 3 metabolites. ZD and PF rats showed significant increases in omega 9 acids but not significant changes in omega 9 metabolites. This study does not indicate that zinc affects the delta 6 desaturase in the metabolism of essential fatty acids. The aberrations previously attributed to zinc deficiency are probably due to the accompanying decreased food intake.     

Carrageenan-induced granuloma and iron status in rats with dietary polyunsaturated fatty acid deficiency

Sprague-Dawley rats were fed for 4 months on a control diet or a polyunsaturated-fatty-acid (PUFA)-deficient diet. The combined effects of iron overload (Fe dextran) or Fe deficiency (desferrioxamine) on carrageenan-induced granuloma were studied. PUFA deficiency induced changes in Fe metabolism, but no alterations in lipid peroxidation variables were observed. Inflammation implied an increase in lipid peroxidation, Fe storage and caeruloplasmin concentration, together with symptoms of anaemia. PUFA deficiency in inflamed rats gave rise to a lower inflammatory response (granuloma weight and prostaglandin E2 concentration) and ethane exhalation. Fe overload potentiated inflammatory and lipid peroxidation processes, whereas Fe deficiency decreased them.     

Short term effects of dietary medium-chain fatty acids and n-3 long-chain polyunsaturated fatty acids on the fat metabolism of healthy volunteers

Background

The amount and quality of dietary fatty acids can modulate the fat metabolism.

Objective

This dietary intervention is based on the different metabolic pathways of long-chain saturated fatty acids (LCFA), which are mostly stored in adipocytic triacylglycerols, medium-chain fatty acids (MCFA) which are preferentially available for hepatic mitochondrial β-oxidation and n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) suggested to modulate fat oxidation and storage by stimulating the peroxisomal β-oxidation. Combined dietary MCFA and n-3 LCPUFA without LCFA may synergistically stimulate fatty acid oxidation resulting in blood lipid clearance and LCFA release from adipocytes.

Design

In a short term, parallel, randomized, double-blind trial effects on the fatty acid metabolism of 10 healthy volunteers (Body Mass Index 25–30) of a formula containing 72% MCFA and 22% n-3 LCPUFA without LCFA (intake: 1.500 kcal/day; fat: 55.5% of energy) were measured in comparison to an isoenergetic formula with equal fat amount and LCFA dominated lipid profile.

Results

The plasma triacylglycerol (p < 0.1) and cholesterol (p < 0.05) content decreased in the test group. The n-3/n-6 LCPUFA (≥ C 20) ratio increased (p < 0.0001) after 4 days treatment. The LCFA content was similar in both groups despite missing LCFA in the test formula indicating LCFA release from adipocytes into the plasma. Both groups significantly reduced body weight considerably 4 kg (p < 0.01) and fat mass up to 50% of weight loss (p < 0.05).

Conclusion

Combined dietary 72% MCFA and 22% n-3 LCPUFA without LCFA stimulate the fatty acid oxidation and release from adipocytes without affecting any safety parameters measured.

     

Species differences in the physiological activity of dietary lignan (sesamin and episesamin) in affecting hepatic fatty acid metabolism

The effect of sesame (Sesamum orientale) lignan preparation containing equivalent amounts of sesamin and episesamin on hepatic fatty acid metabolism was compared in rats, mice and hamsters. Animals were fed on either a diet free of lignan or a diet containing 2 g lignan/kg for 15 d. The lignan preparation greatly increased hepatic activity and the mRNA levels of enzymes involved in fatty acid oxidation, while it strongly down-regulated those of enzymes involved in lipogenesis in rats. In contrast, lignan did not modify these variables in mice and hamsters. Changes observed, if any, were more attenuated in these mice and hamsters than in rats. Sesamin and episesamin concentrations in serum and liver of animals fed on lignan-containing diets were significantly greater (P<0.05) in rats than in mice and hamsters. Moreover, sesamin:episesamin values in tissues were far from that expected from the value in the lignan preparation given to the animals and were dependent on the animal species. Liver microsomes from each animal species degraded sesamin and episesamin in the presence of NADPH. The combined value of sesamin and episesamin degradation rates was lower in rats than in mice and hamsters. In addition, there was considerable diversity in the specificity of the enzyme reaction toward sesamin and episesamin among animal species. The differences in the amounts of lignan remaining in the tissues may account for the species dependence of the physiological activity of sesame lignan in affecting hepatic fatty acid oxidation and synthesis.     

Effect of dietary polyunsaturated/saturated fatty acid ratio and dietary vitamin E on lipid peroxidation in the rat

The effects of the dietary ratio of polyunsaturated/saturated fatty acids (P/S) and dietary vitamin E on lipid peroxidation (LP) were examined to determine whether the vitamin E requirement is elevated by increased P/S in ratios comparable to those found in human diets. Twelve groups of male weanling rats (six/group) were fed purified diets containing 20% fat with P/S ratios of 0.38, 0.82 or 2.30. At each P/S level, groups of rats received either 0, 10, 40 or 100 IU vitamin E/kg diet supplied as all-rac-alpha-tocopherol. After the diets were fed for 16 wk, in vivo LP was assessed by measuring pentane in expired breath. Pentane levels were significantly elevated in rats fed 0 IU vitamin E at all P/S levels. Both 40 and 100 IU vitamin E decreased pentane production to minimal levels for all P/S groups. Liver malondialdehyde levels and in vitro spontaneous red blood cell hemolysis results also indicated a significant effect of vitamin E in reducing in vitro LP, but no overall effect of P/S. Testicular and epididymal histology showed no effect of dietary P/S on the vitamin E requirement. These data demonstrated 40 IU vitamin E to be adequate for maximal inhibition of LP at the P/S levels tested and indicated that these levels of dietary P/S had no significant impact on the vitamin E requirement for the growing rat.     

Dietary long-chain polyunsaturated fatty acids from different sources affect fat and fatty acid excretions in rats.

Several sources of long-chain polyunsaturated fatty acids (LCP) have been evaluated for infant-formula supplementation. These sources differ in their chemical structure [triglyceride (TG) or phospholipid (PL)], arrangement of fatty acids on the TG or PL backbone, fatty acid composition and presence of other lipid components. All of these characteristics influence fat digestion, may affect fat and fatty acid absorption, and hence, LCP bioavailability and metabolism in infancy. The main objective of this work was to establish the influence of different dietary LCP sources on overall fat and LCP absorption in early life. We compared fat and fatty acid excretions at weaning in rats fed control diets or diets supplemented with LCP as TG or PL. Two separate experiments were conducted. In Experiment 1, weanling rats were fed for 3 wk a control diet (C1), a diet with TG from tuna and fungal oils (TF-TG) or a diet with PL from pig brain concentrate (PB-PL). In Experiment 2, weanling rats were fed for 3 wk a control diet (C2), a diet containing egg-TG (EG-TG) or a diet containing egg-PL (EG-PL). Fat, mineral and saturated fatty acid excretions in feces were higher in rats fed PB-PL compared with those fed TF-TG diet. In Experiment 2, groups did not differ in fat and mineral excretions. However, the EG-PL group had lower fecal excretions of saturated fatty acids than the C2 and EG-TG groups. The 16:1(n-7), 18:1(n-9), 18:2(n-6) and 22:6(n-3) levels in feces were higher in the EG-TG group than in the EG-PL group. In summary, total fat and LCP excretions differed among rats fed diets supplemented with LCP from different sources.     

Effects of sesamin and curcumin on delta 5-desaturation and chain elongation of polyunsaturated fatty acid metabolism in primary cultured rat hepatocytes.

Effects of sesamin and curcumin on delta 5-desaturation and chain elongation of polyunsaturated fatty acid (PUFA) were studied in rat primary cultured hepatocytes. When sesamin was added to culture medium containing 20:4 (n-3), rat hepatocytes after 24 h of incubation produced 20:5 (n-3) from 20:4 (n-3), whereas when incubated with 20:3 (n-6), the metabolite by delta 5-desaturation did not accumulate, and consequently, the ratio of 20:3 (n-6)/20:4 (n-6) increased with the amount of sesamin added. Curcumin was more effective than sesamin in this respect. Both sesamin and curcumin interfered with chain elongation of PUFAs. An addition of 18:3 (n-6) or 18:4 (n-3) increased the cellular concentrations of 20:3 (n-6) or 20:4 (n-3), respectively, but the simultaneous addition of sesamin or curcumin inhibited the chain elongation of C18 acids (the fatty acids with 18 carbons) into corresponding C20 and C18 acids. Similarly, the elongation from C20 of n-3 and n-6 families to C22 was also inhibited with sesamin and curcumin. These results suggested that: 1) sesamin and curcumin inhibited delta 5-desaturation of n-6 fatty acid, but not n-3 fatty acid in rat hepatocytes; 2) curcumin was more effective than sesamin; 3) chain elongation was also inhibited by sesamin and curcumin.     

Comparative analysis of sesame lignans (sesamin and sesamolin) in affecting hepatic fatty acid metabolism in rats

Effects of sesamin and sesamolin (sesame lignans) on hepatic fatty acid metabolism were compared in rats. Rats were fed either a lignan-free diet, a diet containing 0.6 or 2 g/kg lignan (sesamin or sesamolin), or a diet containing both sesamin (1.4 g/kg) and sesamolin (0.6 g/kg) for 10 d. Sesamin and sesamolin dose-dependently increased the activity and mRNA abundance of various enzymes involved in hepatic fatty acid oxidation. The increase was much greater with sesamolin than with sesamin. These lignans increased parameters of hepatic fatty acid oxidation in an additive manner when added simultaneously to an experimental diet. In contrast, they decreased the activity and mRNA abundance of hepatic lipogenic enzymes despite dose-dependent effects not being necessarily obvious. Sesamin and sesamolin were equally effective in lowering parameters of lipogenesis. Sesamolin accumulated in serum at 33- and 46-fold the level of sesamin at dietary concentrations of 0.6 and 2 g/kg, respectively. The amount of sesamolin accumulated in liver was 10- and 7-fold that of sesamin at the respective dietary levels. Sesamolin rather than sesamin can account for the potent physiological effect of sesame seeds in increasing hepatic fatty acid oxidation observed previously. Differences in bioavailability may contribute to the divergent effects of sesamin and sesamolin on hepatic fatty acid oxidation. Sesamin compared to sesamolin was more effective in reducing serum and liver lipid levels despite sesamolin more strongly increasing hepatic fatty acid oxidation.     

膳食n-6/n-3脂肪酸比值对小鼠淋巴细胞脂肪酸构成和功能的影响

目的观察膳食n6n3脂肪酸比值对淋巴细胞脂肪酸构成及细胞功能的影响。方法BALBc小鼠随机分为5组n6n3比值分别为1(A组)、75(B组)、15(C组)、30(D组)和正常对照组,其中实验组S∶M∶P模拟中国居民膳食脂肪酸摄入的S∶M∶P为1∶15∶1,正常对照组为AIN93G配方的1∶15∶37。基础饲料采用AIN93G配方,脂肪酸构成以食用油脂调配。饲养12周。测定小鼠T淋巴细胞功能,脾淋巴细胞脂肪酸构成、PGE2水平。结果n6n3比值接近1时,小鼠T淋巴细胞增殖活性、CD4+、CD8+T细胞比例、培养上清IL2、PGE2水平显著降低;淋巴细胞C18∶2、C20∶4、n6PUFA含量显著减少;C22∶6、C16∶1、C18∶1、总MUFA含量明显高于其他实验组。淋巴细胞C22∶6含量与淋巴细胞增殖活性显著负相关;C20∶5含量与CD4+T淋巴细胞比例、IL2水平显著负相关;C16∶1含量与CD4+、CD8+T淋巴细胞比例显著负相关。结论小鼠脾淋巴细胞的脂肪酸构成受膳食脂肪酸构成的影响;n6n3比值为1组与比值为30的膳食组相比较,小鼠T淋巴细胞增殖活性受到抑制。     

ω-3多不饱和脂肪酸对内毒素致大鼠急性肺损伤的影响

目的 观察肠道给予ω-3多不饱和脂肪酸（PUFA）对脂多糖（LPS）诱导的大鼠急性肺损伤模型的作用。方法 将58只雄性SD大鼠分为5组：空白对照组（n=10）,模型组（各组n=12）,ω-3 PUFA高、中、低剂量组（各组n=12）。造模前7 d开始,ω-3 PUFA高、中、低剂量组分别口服灌胃ω-3 PUFA 1、0.5、0.25 g/kg 体重,1次/d,连续 7 d。末次给药后 24 h,除空白对照组外,其余各组大鼠尾静脉注射LPS（6 mg/kg）造成急性肺损伤模型,造模后观察大鼠一般情况。0、6、24 h测量大鼠体温。造模 24 h后眼静脉丛采血检测血常规和血生化指标。大鼠活杀后取左叶肺称量湿重、干重和湿/干重比（W/D）,取右叶肺做光学显微镜下病理学观察,计算半定量病理指数（PI）。结果 造模 24 h后,除空白对照组外其他各组均有死亡,各组指标按n=10计算。大鼠注射LPS后均出现蜷卧少动等症状。6 h时模型组体温明显高于空白对照组［（37.4±0.27）℃比（35.9±0.05）℃,P=0.00］;ω-3 PUFA高、中、低剂量组体温分别为（36.2±0.38）、（36.3±0.30）、（36.3±0.32）℃,均显著低于模型组（P均=0.01）。模型组白细胞、中性粒细胞和淋巴细胞计数均升高,但与其他组比较,差异无统计学意义。模型组血清谷草转氨酶（GOT）和谷丙转氨酶（GPT）水平明显高于空白对照组［（353±235）U/L比（157±55）U/L,P=0.02;（141±103）U/L比（54±23）U/L,P=0.03］,ω-3 PUFA高剂量组的GOT和GPT水平低于模型组［（167±94）U/L,P=0.03;（63±57）U/L,P=0.04］。模型组大鼠肺湿重;（371±38）mg比（281±24）mg,P=0.01］和W/D均显著高于空白对照组（7.34±1.40比5.41±0.84,P=0.01）;ω-3 PUFA高、中、低剂量组W/D较模型组显著降低（6.17±0.58,P=0.03;6.17±0.76,P=0.03;6.13±1.23,P=0.04）。光学显微镜下观察,模型组肺泡因充血而明显扩张,间质可见散在炎性细胞浸润;ω-3 PUFA各组大部分肺泡结构尚好。模型组PI值显著高于空白对照组（3.9±0.9比0.0±0.0,P=0.00）,ω-3 PUFA高、中、低剂量组PI值均显著低于模型组（2.1±0.3、2.1±0.3、2.3±0.5,P均=0.01）。 结论LPS可成功建立大鼠急性肺损伤模型。高、中、低剂量ω-3 PUFA均可改善大鼠急性肺损伤。早期肠道给予ω-3 PUFA可减轻LPS诱导的急性肺损伤,理想的干预时机及剂量仍需进一步研究。     

葡多酚对高脂膳大鼠血脂与脂质过氧化的影向

目的　观察葡多酚 (GPC)对饲以高脂膳食、乙醇等不同膳食的大鼠血脂及脂质过氧化的影响。方法　将大鼠随机分为正常对照组、高脂膳组、高脂乙醇组、高脂GPC组、高脂乙醇GPC(高、低剂量 )组、高脂乙醇VE组 7个组 ,喂养 6周 ,测定血清甘油三脂 (TG)、总胆固醇 (TC)、高密度脂蛋白胆固醇 (HDL -C)、低密度脂蛋白胆固醇 (LDL -C)、活性氧 (ROS)、丙二醛 (MDA)水平及超氧化物歧化酶 (SOD)活性等指标。结果　高脂组、高脂乙醇组的血清TG、TC、ROS、MDA水平均较实验前显著性升高 ;同高脂乙醇组比较 ,高脂乙醇高GPC组的血清TC、MDA水平均显著性降低 ,SOD活性显著性升高 (P <0 0 5 )。结论　GPC对乙醇与高脂膳食引起的血脂水平升高和脂质过氧化均有一定的抑制作用。