Marine fish oil is more potent than plant-based n-3 polyunsaturated fatty acids in the prevention of mammary tumors

Marine-derived n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to inhibit mammary carcinogenesis. However, evidence regarding plant-based α-linolenic acid (ALA), the major n-3 PUFA in the Western diet, remains equivocal. The objective of this study was to examine the effect of lifelong exposure to plant- or marine-derived n-3 PUFAs on pubertal mammary gland and tumor development in MMTV-neu(ndl)-YD5 mice. It is hypothesized that lifelong exposure to n-3 PUFA reduces terminal end buds during puberty leading to delayed tumor onset, volume and multiplicity. It is further hypothesized that plant-derived n-3 PUFAs will exert dose-dependent effects. Harems of MMTV-FVB males were bred with wild-type females and fed either a (1) 10% safflower (10% SF, n-6 PUFA, control), (2) 10% flaxseed (10% FS), (3) 7% safflower plus 3% flaxseed (3% FS) or (4) 7% safflower plus 3% menhaden (3% FO) diet. Female offspring were maintained on parental diets. Compared to SF, 10% FS and 3% FO reduced (P<.05) terminal end buds at 6 weeks and tumor volume and multiplicity at 20 weeks. A dose-dependent reduction of tumor volume and multiplicity was observed in mice fed 3% and 10% FS. Antitumorigenic effects were associated with altered HER2, pHER-2, pAkt and Ki-67 protein expression. Compared to 10% SF, 3% FO significantly down-regulated expression of genes involved in eicosanoid synthesis and inflammation. From this, it can be estimated that ALA was 1/8 as potent as EPA+DHA. Thus, marine-derived n-3 PUFAs have greater potency versus plant-based n-3 PUFAs.     

The Fat-1 Mouse has Brain Docosahexaenoic Acid Levels Achievable Through Fish Oil Feeding

Fat-1 transgenic mice endogenously convert n-6 to n-3 polyunsaturated fatty acids (PUFA). The aims of this study were to test whether a) fish oil feeding can attain similar brain n-3 PUFA levels as the fat-1 mouse, and b) fat-1 mouse brain docosahexaenoic acid (22:6n-3; DHA) levels can be potentiated by fish oil feeding. Fat-1 mice and their wildtype littermates consumed either a 10% safflower oil (SO) or a 2% fish oil and 8% safflower oil chow (FO). Brain total lipid and phospholipid fraction fatty acids were analyzed using GC-FID. Wildtype mice fed FO chow had similar brain levels of DHA as fat-1 mice fed SO chow. Fat-1 mice fed FO chow had similar brain n-3 PUFA levels as fat-1 mice fed SO chow. In conclusion, brain levels of DHA in the fat-1 mouse can be obtained by and were not further augmented with fish oil feeding.     

Studies of UCP2 transgenic and knockout mice reveal that liver UCP2 is not essential for the antiobesity effects of fish oil

Uncoupling protein 2 (UCP2) is a possible target molecule for energy dissipation. Many dietary fats, including safflower oil and lard, induce obesity in C57BL/6 mice, whereas fish oil does not. Fish oil increases UCP2 expression in hepatocytes and may enhance UCP2 activity by activating the UCP2 molecule or altering the lipid bilayer environment. To examine the role of liver UCP2 in obesity, we created transgenic mice that overexpressed human UCP2 in hepatocytes and examined whether UCP2 transgenic mice showed less obesity when fed a high-fat diet (safflower oil or lard). In addition, we examined whether fish oil had antiobesity effects in UCP2 knockout mice. UCP2 transgenic and wild-type mice fed a high-fat diet (safflower oil or lard) developed obesity to a similar degree. UCP2 knockout and wild-type mice fed fish oil had lower rates of obesity than mice fed safflower oil. Remarkably, safflower oil did not induce obesity in female UCP2 knockout mice, an unexpected phenotype for which we presently have no explanation. However, this unexpected effect was not observed in male UCP2 knockout mice or in UCP2 knockout mice fed a high-lard diet. These data indicate that liver UCP2 is not essential for fish oil-induced decreases in body fat.     

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.     

Levels of plasma insulin, leptin and adiponectin, and activities of key enzymes in carbohydrate metabolism in skeletal muscle and liver in fasted ICR mice fed dietary n-3 polyunsaturated fatty acids

The aim of this study was to clarify the mechanisms related to plasma glucose concentration in mice fed a diet rich in n-3 polyunsaturated fatty acids (n-3 PUFAs). Male Crlj:CD-1 (ICR) mice were fed experimental diets containing 6% lard (LD), 6% fish oil (FO) or 4.1% lard plus 1.5% docosahexaenoic acid ethyl ester and 0.4% eicosapentaenoic acid ethyl ester (DE) for 12 weeks. There were no marked differences in plasma glucose and insulin concentration changes on glucose tolerance test between the three dietary groups. At the end of the feeding trial, plasma glucose concentration was significantly lower in fasted mice in the FO group than in those in the LD group (P<.005). Plasma adiponectin concentration was significantly higher in the FO group than in the LD group (P<.05). Hexokinase, phosphofructokinase, glucose-6-phosphate dehydrogenase and glycerophosphate dehydrogenase activities in skeletal muscle tended to be lower in the FO group than in the LD group, while there were no differences in glucokinase and phosphofructokinase activities in liver between the three dietary groups. However, hepatic glycerophosphate dehydrogenase activity was 53-fold and 4.2-fold higher in the FO group than in the LD and DE groups, respectively (P<.0005 and P<.05, respectively). These results suggest that the reduction in plasma glucose concentration in mice fed n-3 PUFAs is mainly caused by acceleration of glucose uptake and glycerol synthesis in the liver rather than in the skeletal muscle.     

Sucrose counteracts the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice

Background

Polyunsaturated n-3 fatty acids (n-3 PUFAs) are reported to protect against high fat diet-induced obesity and inflammation in adipose tissue. Here we aimed to investigate if the amount of sucrose in the background diet influences the ability of n-3 PUFAs to protect against diet-induced obesity, adipose tissue inflammation and glucose intolerance.

Methodology/Principal Findings

We fed C57BL/6J mice a protein- (casein) or sucrose-based high fat diet supplemented with fish oil or corn oil for 9 weeks. Irrespective of the fatty acid source, mice fed diets rich in sucrose became obese whereas mice fed high protein diets remained lean. Inclusion of sucrose in the diet also counteracted the well-known anti-inflammatory effect of fish oil in adipose tissue, but did not impair the ability of fish oil to prevent accumulation of fat in the liver. Calculation of HOMA-IR indicated that mice fed high levels of proteins remained insulin sensitive, whereas insulin sensitivity was reduced in the obese mice fed sucrose irrespectively of the fat source. We show that a high fat diet decreased glucose tolerance in the mice independently of both obesity and dietary levels of n-3 PUFAs and sucrose. Of note, increasing the protein∶sucrose ratio in high fat diets decreased energy efficiency irrespective of fat source. This was accompanied by increased expression of Ppargc1a (peroxisome proliferator-activated receptor, gamma, coactivator 1 alpha) and increased gluconeogenesis in the fed state.

Conclusions/Significance

The background diet influence the ability of n-3 PUFAs to protect against development of obesity, glucose intolerance and adipose tissue inflammation. High levels of dietary sucrose counteract the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice.     

Maternal high fat diet is associated with decreased plasma n-3 fatty acids and fetal hepatic apoptosis in nonhuman primates

To begin to understand the contributions of maternal obesity and over-nutrition to human development and the early origins of obesity, we utilized a non-human primate model to investigate the effects of maternal high-fat feeding and obesity on breast milk, maternal and fetal plasma fatty acid composition and fetal hepatic development. While the high-fat diet (HFD) contained equivalent levels of n-3 fatty acids (FA's) and higher levels of n-6 FA's than the control diet (CTR), we found significant decreases in docosahexaenoic acid (DHA) and total n-3 FA's in HFD maternal and fetal plasma. Furthermore, the HFD fetal plasma n-6:n-3 ratio was elevated and was significantly correlated to the maternal plasma n-6:n-3 ratio and maternal hyperinsulinemia. Hepatic apoptosis was also increased in the HFD fetal liver. Switching HFD females to a CTR diet during a subsequent pregnancy normalized fetal DHA, n-3 FA's and fetal hepatic apoptosis to CTR levels. Breast milk from HFD dams contained lower levels of eicosopentanoic acid (EPA) and DHA and lower levels of total protein than CTR breast milk. This study links chronic maternal consumption of a HFD with fetal hepatic apoptosis and suggests that a potentially pathological maternal fatty acid milieu is replicated in the developing fetal circulation in the nonhuman primate.     

Partial replacement of dietary fish oil with blends of vegetable oils (rapeseed, linseed and palm oils) in diets for European sea bass (Dicentrarchus labrax L.) over a long term growth study: effects on muscle and liver fatty acid composition and effectiveness of a fish oil finishing diet

Triplicate groups of European sea bass (Dicentrarchus labrax L.), of initial mass 5 g, were fed one of three practical type diets for 64 weeks. The three diets differed only in the added oil and were 100% fish oil (FO; diet A), 40% FO/60% vegetable oil blend (VO; diet B) where the VO blend was rapeseed oil, linseed oil and palm oil in the ratio 10/35/15 by weight and 40% FO/60% VO blend (diet C) where the ratio was 24/24/12 by weight. After final sample collection the remaining fish were switched to a 100% FO finishing diet for a further 20 weeks. After 64 weeks fish fed 60% VO diet B had significantly lower live mass and liver mass than fish fed diets A and C although SGR, FCR and length were not different between groups. There were no differences in any of the above parameters after either 14 or 20 weeks on the FO finishing diet. Fatty acid compositions of flesh were correlated to dietary fatty acids although there was selective retention of docosahexaenoic acid (22:6n-3; DHA) regardless of dietary input. Inclusion of dietary VO resulted in significantly reduced flesh levels of DHA and eicosapentaenoic acid (20:5n-3; EPA) while 18:1n-9, 18:2n-6 and 18:3n-3 were all significantly increased in fish fed the 60% VO diets. Fatty acid compositions of liver showed broadly similar changes, as a result of dietary fatty acid composition, as was seen in flesh. However, the response of flesh and liver to feeding a FO finishing diet was different. In flesh, DHA and EPA values were not restored after 14 or 20 weeks of feeding a FO finishing diet with the values in fish fed the two 60% VO diets being around 70% of the values seen in fish fed FO throughout. Conversely, and despite liver DHA and EPA levels being reduced to only 40% of the value seen in fish fed 100% FO after 64 weeks, the levels of liver DHA and EPA were not significantly different between treatments after feeding the FO finishing diet for 14 weeks. However, a 200 g portion of sea bass flesh, after feeding the experimental diets for 64 weeks followed by a FO diet for 14 weeks, contained 1.22 and 0.95 g of EPA + DHA for fish fed FO or 60% VO, respectively. Therefore, sea bass grown for most of the production cycle using diets containing 60% VO can still contribute a significant quantity of healthy n-3 HUFA to the human consumer.     

N-3 PUFAs inhibited hepatic ER stress induced by feeding of a high-saturated fat diet accompanied by the expression LOX-1

Excessive consumption of saturated fat leads to non-alcoholic fatty liver disease (NAFLD), which is attenuated by supplementation of n-3 polyunsaturated fatty acids (PUFAs). Endoplasmic reticulum (ER) stress is crucial in the development of NAFLD, but how high-saturated fat diet (HFD) causes ER stress and NAFLD remains unclear. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved in hepatic ER stress. We aimed to explore the roles of LOX-1 in HFD-induced ER stress. Male Sprague–Dawley rats were fed an HFD without or with supplementation of fish oil for 16 weeks. The effects of n-3 PUFAs on hepatic ER stress degrees and the expression levels of LOX-1 were examined. Then human L02 hepatoma cells were treated with palmitate or palmitate and DHA to determine the ER stress and LOX-1 expression levels in vitro. After that the expression of LOX-1 in L02 cells was either knocked-down or overexpressed to analyze the roles of LOX-1 in palmitate-induced ER stress. The feeding of HFD induced NAFLD development and ER stress in the liver, and LOX-1 expressing level, which were all reversed by fish oil supplementation. In vitro, DHA treatment reduced the expression of LOX-1, and palmitate-induced ER stress. SiRNA-mediated knock-down of LOX-1 inhibited palmitate-induced ER stress, whereas overexpression of LOX-1 dramatically induced ER stress in L02 cells.LOX-1 is critical for HFD-induced ER stress, and inhibition of its expression under the treatment of n-3 PUFAs could ameliorate HFD-induced NAFLD.     

Dietary long-chain n-3 PUFAs mitigate CD4+ T cell/adipocyte inflammatory interactions in co-culture models of obese adipose tissue

Obese adipose tissue (AT) inflammation is partly driven by accumulation of CD4⁺ T helper (Th)1 cells and reduced Th2 and T regulatory subsets, which promotes macrophage chemotaxis and ensuing AT metabolic dysfunction. This study investigated CD4⁺ T cell/adipocyte cytokine-mediated paracrine interactions (cross talk) as a target for dietary intervention to mitigate obese AT inflammation. Using an in vitro co-culture model designed to recapitulate CD4⁺ T cell accumulation in obese AT (5% of stromal vascular cellular fraction), 3T3-L1 adipocytes were co-cultured with purified splenic CD4⁺ T cells from C57Bl/6 mice consuming one of two isocaloric diets containing either 10% w/w safflower oil (control, CON) or 7% w/w safflower oil+3% w/w fish oil (FO) for 4 weeks (n=8–11/diet). The FO diet provided 1.9% kcal from the long-chain (LC) n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid and docosahexaenoic acid, a dose that can be achieved by supplementation. Co-cultures were stimulated for 48 h with lipopolysaccharide (LPS) to mimic in vivo obese endotoxin levels or with conditioned media collected from LPS-stimulated visceral AT isolated from CON-fed mice. In both stimulation conditions, FO reduced mRNA expression and/or secreted protein levels of Th1 markers (T-bet, IFN-γ) and increased Th2 markers (GATA3, IL-4), concomitant with reduced inflammatory cytokines (IL-1β, IL-6, IL-12p70, TNF-α), macrophage chemokines (MCP-1, MCP-3, MIP-1α, MIP-2) and levels of activated central regulators of inflammatory signaling (NF-κB, STAT-1, STAT-3) (P<.05). Therefore, CD4⁺ T cell/adipocyte cross talk represents a potential target for LC n-3 PUFAs to mitigate obese AT inflammation.     

Dietary ratio of n-6/n-3 PUFAs and docosahexaenoic acid: actions on bone mineral and serum biomarkers in ovariectomized rats

Hypoestrogenic states escalate bone loss in animals and humans. This study evaluated the effects of the amount and ratio of dietary n-6 and n-3 polyunsaturated fatty acids (PUFAs) on bone mineral in 3-month-old sexually mature ovariectomized (OVX) Sprague-Dawley rats. For 12 weeks, the rats were fed either a high-PUFA (HP) or a low-PUFA (LP) diet with a ratio of n-6/n-3 PUFAs of 5:1 (HP5 and LP5) or 10:1 (HP10 and LP10). All diets (modified AIN-93G) provided 110.4 g/kg of fat from safflower oil and/or high-oleate safflower oil blended with n-3 PUFAs (DHASCO oil) as a source of docosahexaenoic acid (DHA). Fatty acid analyses confirmed that the dietary ratio of 5:1 significantly elevated the amount of DHA in the periosteum, marrow and cortical and trabecular bones of the femur. Dual-energy X-ray absorptiometry measurements for femur and tibia bone mineral content (BMC) and bone mineral density showed that the DHA-rich diets (HP5 and LP5) resulted in a significantly lower bone loss among the OVX rats at 12 weeks. Rats fed the LP diets displayed the lowest overall serum concentrations of the bone resorption biomarkers pyridinoline (Pyd) and deoxypyridinoline, whereas the bone formation marker osteocalcin was lowest in the HP groups. Regardless of the dietary PUFA content, DHA in the 5:1 diets (HP5 and LP5) preserved rat femur BMC in the absence of estrogen. This study indicates that the dietary ratio of n-6/n-3 PUFAs (LP5 and HP5) and bone tissue concentration of total long-chain n-3 PUFAs (DHA) minimize femur bone loss as evidenced by a higher BMC in OVX rats. These findings show that dietary DHA lowers the ratio of 18:2n-6 (linoleic acid)/n-3 in bone compartments and that this ratio in tissue correlates with reduced Pyd but higher bone alkaline phosphatase activity and BMC values that favor bone conservation in OVX rats.     

High ratio of ω-3/ω-6 polyunsaturated fatty acids targets mTORC1 to prevent high-fat diet-induced metabolic syndrome and mitochondrial dysfunction in mice

Adjusting ω-3/ω-6 polyunsaturated fatty acids (PUFAs) ratio in high-fat diet is one potential mean to improve metabolic syndrome; however, underlying mechanisms remain unclear. Four groups of mice were fed 60% kcal diets with saturated fatty acids, three different ω-3/ω-6 PUFAs ratios (low, middle and high) for 12 weeks, respectively. Body weight, atherosclerosis marker, insulin signal index and level of lipid accumulation in liver were significantly lowered in High group compared with saturated fatty acids group and Low group at week 12. Expressions of p-mTOR and raptor were inhibited by high ω-3 PUFAs. Importantly, ω-3 PUFAs intake up-regulated mitochondrial electron transport chain and tricarboxylic acid cycle pathway through metabolomics analysis in liver. Mitochondrial complexes activities were raised, fumaric acid was reduced and oxidative stress was alleviated in High group. We conclude that consuming long-term high-fat diet with same calories but high ω-3/ω-6 PUFAs ratio relieves metabolic syndrome by regulating mTORC1 pathway to enhance mitochondrial function.     

Effect of dietary oils enriched with n-3 fatty acids on survival of mice

Female mice were fed a conventional diet, shifted at 119 days of age to a diet supplemented with 10 wt % lard (Lar), high-linoleic (n-6) safflower oil (Saf), rapeseed oil (low-erucic, Rap), high-alpha-linolenic (n-3) perilla oil (Per) or a mixture (1:9) of ethyl docosahexaenoate (n-3) and soybean oil (DHA/Soy). Weight gain was less in the Per group than in the other groups at 497 days of age. In the Rap group, proteinuria was more severe than in the Saf, Per and DHA/Soy group, and hepatic triacylglycerol accumulation was greater than in the other groups. The mean survival time of the DHA/Soy group (753 days) was significantly longer than in the Lar group (672 days) and Saf group (689 days); the differences among other groups (e.g., 701 days in the Per group and 712 days in the Rap group) were not statistically significant. Although DHA is more susceptible to auto-oxidation than other major fatty acids in the air, an oil containing DHA was found to increase the survival of mice. Rapeseed oil that decreases the survival time of SHRSP rats was found to be safe in the mouse strain used in this study when survival was an end point.     

Effect of rapeseed oil and dietary n-3 fatty acids on triacylglycerol synthesis and secretion in Atlantic salmon hepatocytes

Fish oil (FO) has traditionally been used as the dominating lipid component in fish feed. However, FO is a limited resource and the price varies considerably, which has led to an interest in using alternative oils, such as vegetable oils (VOs), in fish diets. It is far from clear how these VOs affect liver lipid secretion and fish health. The polyunsaturated fatty acids (PUFAs), eicosapentanoic acid (EPA) and docosahexanioc acid (DHA), reduce the secretion of lipoproteins rich in triacylglycerols (TAGs) in Atlantic salmon, as they do in humans. The mechanism by which n-3 fatty acids (FAs) in the diet reduce TAG secretion is not known. We have therefore investigated the effects of rapeseed oil (RO) and n-3 rich diets on the accumulation and secretion of (3)H-glycerolipids by salmon hepatocytes. Salmon, of approximately 90 g were fed for 17 weeks on one of four diets supplemented with either 13.5% FO, RO, EPA-enriched oil or DHA-enriched oil until a final average weight of 310 g. Our results show that the dietary FA composition markedly influences the endogenous FA composition and lipid content of the hepatocytes. The intracellular lipid level in hepatocytes from fish fed RO diet and DHA diet were higher, and the expressions of the genes for microsomal transfer protein (MTP) and apolipoprotein A1 (Apo A1) were lower, than those in fish fed the two other diets. Secretion of hepatocyte glycerolipids was lower in fish fed the EPA diet and DHA diet than it was in fish fed the RO diet. Our results indicate that EPA and DHA possess different hypolipidemic properties. Both EPA and DHA inhibit TAG synthesis and secretion, but only EPA induces mitochondrial proliferation and reduce intracellular lipid. Expression of the gene for peroxisome proliferator-activated receptor alpha (PPARalpha) was higher in the DHA dietary group than it was in the other groups.     

Dietary sphingomyelin attenuates hepatic steatosis and adipose tissue inflammation in high-fat-diet-induced obese mice

Western-type diets can induce obesity and related conditions such as dyslipidemia, insulin resistance and hepatic steatosis. We evaluated the effects of milk sphingomyelin (SM) and egg SM on diet-induced obesity, the development of hepatic steatosis and adipose inflammation in C57BL/6J mice fed a high-fat, cholesterol-enriched diet for 10 weeks. Mice were fed a low-fat diet (10% kcal from fat) (n=10), a high-fat diet (60% kcal from fat) (HFD, n=14) or a high-fat diet modified to contain either 0.1% (w/w) milk SM (n=14) or 0.1% (w/w) egg SM (n=14). After 10 weeks, egg SM ameliorated weight gain, hypercholesterolemia and hyperglycemia induced by HFD. Both egg SM and milk SM attenuated hepatic steatosis development, with significantly lower hepatic triglycerides (TGs) and cholesterol relative to HFD. This reduction in hepatic steatosis was stronger with egg SM supplementation relative to milk SM. Reductions in hepatic TGs observed with dietary SM were associated with lower hepatic mRNA expression of PPARγ-related genes: Scd1 and Pparg2 in both SM groups, and Cd36 and Fabp4 with egg SM. Egg SM and, to a lesser extent, milk SM reduced inflammation and markers of macrophage infiltration in adipose tissue. Egg SM also reduced skeletal muscle TG content compared to HFD. Overall, the current study provides evidence of dietary SM improving metabolic complications associated with diet-induced obesity in mice. Further research is warranted to understand the differences in bioactivity observed between egg and milk SM.     

Dietary docosahexaenoic acid ameliorates, but rapeseed oil and safflower oil accelerate renal injury in stroke-prone spontaneously hypertensive rats as compared with soybean oil, which is associated with expression for renal transforming growth factor-beta, fibronectin and renin

We have noted that n-3 fatty acid-rich oils, such as fish oil, perilla oil and flaxseed oil as well as ethyl docosahexaenoate (DHA) prolonged the survival time of stroke-prone spontaneously hypertensive rats (SHRSP) rats by approximately 10% as compared with linoleate (n-6)-rich safflower oil. Rapeseed oil with a relatively low n-6/n-3 ratio unusually shortened the survival time by approximately 40%, suggesting the presence of minor components unfavorable to SHRSP rats. This study examined the effects of dietary oils and DHA on renal injury and gene expression related to renal injury in SHRSP rats. Rats fed rapeseed oil- and safflower oil-supplemented diets developed more severe proteinuria than those fed soybean oil-supplemented diet used as a control, but there were no significant differences in blood pressure. In contrast, the DHA-supplemented diet inhibited the development of proteinuria and suppressed hypertension. The mRNA levels for renal TGF-beta, fibronectin and renin were higher in the rapeseed oil and safflower oil groups after 9 weeks of feeding of the experimental diet than in the soybean oil and DHA groups. The fatty acid composition of kidney phospholipids was markedly affected by these diets. These results indicate that the renal injury observed in the groups fed safflower oil with a high n-6/n-3 ratio and rapeseed oil with presumed minor components is accompanied by increased expression of the TGF-beta, renin and fibronectin genes, and that dietary DHA suppresses renal injury and gene expression as compared with soybean oil.     

裂殖壶藻藻油DHA对高脂饮食诱导肥胖小鼠的影响

【目的】肥胖症是一种慢性代谢类疾病,具有较高的发病率和高危后果。研究表明,n-3多不饱和脂肪酸(n-3 Polyunsaturated fatty acids,n-3 PUFAs),特别是二十二碳六烯酸(Docosahexaenoic acid,DHA)对与肥胖症相关疾病有较好的防治效果,对体内脂质代谢有重要的调节作用。探讨裂殖壶藻(Schizochytrium sp.)藻油DHA对高脂饮食诱导肥胖小鼠体重、脂肪组织重量、血脂、肝和脂肪组织病理形态和脂质代谢相关基因表达的影响。【方法】通过高脂饮食建立小鼠肥胖模型,以体重增幅15%为标准分出肥胖小鼠。试验共分五组:(1)低脂对照组;(2)高脂模型组;(3)高脂+低剂量藻油组(50 mg DHA/kg);(4)高脂+中剂量藻油组(100 mg DHA/kg);(5)高脂+高剂量藻油组(200 mg DHA/kg)。其中,藻油处理组灌服相应剂量藻油,低脂对照组和高脂模型组灌胃同等体积玉米油。处理9周后,腹腔麻醉,摘眼球取血并分离血清,测血清中甘油三酯、胆固醇和高密度脂蛋白含量;之后处死小鼠,分离附睾、肾周和肠系膜脂肪组织及肝脏,称湿重;附睾脂肪和肝组织切片进行HE染色,观察病理变化情况;利用RT-PCR检测附睾脂肪组织中激素敏感脂酶(Hormone sensitive lipase,HSL)基因的m RNA表达情况。【结果】藻油处理组小鼠体重没有显著下降,但是腹部脂肪重量显著降低、脂肪细胞体积明显小于高脂模型组;同时血清中甘油三酯、胆固醇含量显著降低,肝组织异位脂肪堆积明显减少;脂肪组织中HSL基因的表达水平显著提高。【结论】裂殖壶藻藻油DHA处理能显著降低高脂饮食导致的小鼠腹部脂肪积累并改善血脂,可能有利于肥胖症的防治。     

Effects of dietary fat and zinc on adiposity,serum leptin and adipose fatty acid composition in C57BL/6J mice

Zinc (Zn) has been implicated in altered adipose metabolism, insulin resistance and obesity. The objective of this study was to investigate the effects dietary Zn deficiency and supplementation on adiposity, serum leptin and fatty acid composition of adipose triglycerides and phospholipid in C57BL/6J mice fed low-fat (LF) or high-fat (HF) diets for a 16 week period. Weanling C57BL/6J mice were fed LF (16% kcal from soybean oil) or HF (39% kcal from lard and 16% kcal from soybean oil) diets containing 3, 30 or 150 mg Zn/kg diet (ZD = Zn-deficient, ZC = Zn control and ZS = Zn-supplemented, respectively). HF-fed mice had higher fat pad weights and lower adipose Zn concentrations than the LF-fed mice. The ZD and ZS groups had a reduced content of fatty acids in adipose triglycerides compared to the ZC group, suggesting that zinc status may influence fatty acid accumulation in adipose tissue. Serum leptin concentration was positively correlated with body weight and body fat, and negatively correlated with adipose Zn concentration. Dietary fat, but not dietary Zn, altered the fatty acid composition of adipose tissue phospholipid and triglyceride despite differences in Zn status assessed by femur Zn concentrations. The fatty acid profile of adipose triglycerides generally reflected the diets. HF-fed mice had a higher percentage of C20:4 n-6, elevated ratio of n-6/n-3, lower ratio of PUFA/SAT and reduced percentage of total n-3 fatty acids in adipose phospholipid, a fatty acid profile associated with obesity-induced risks for insulin resistance and impaired glucose transport. In summary, the reduced adipose Zn concentrations in HF-fed mice and the negative correlation between serum leptin and adipose Zn concentrations support an interrelationship among obesity, leptin and Zn metabolism.