Effect of saturated, omega-3 and omega-6 polyunsaturated fatty acids on myocardial infarction

Dietary fatty acids have cholesterol lowering, antiatherogenic, and antiarrhythmic properties that decrease the risk of myocardial infarction (MI). This study was designed to study the effects of various oils rich in either polyunsaturated (omega-3 or omega-6) fatty acids (PUFA) or saturated fatty acids (SFA) on the severity of experimentally induced MI. Male albino Sprague-Dawley rats (100-150 g; n = 20) were fed diets enriched with fish oil (omega-3 PUFA), peanut oil (omega-6 PUFA), or coconut oil (SFA) for 60 days. Experimental MI was induced with isoproterenol. Mortality rates; serum enzymes aspartate amino transferase; alanine amino transferase; creatine phosphokinase (CPK); lipid profiles in serum, myocardium, and aorta; peroxide levels in heart and aorta; activities of catalase and superoxide dismutase; and levels of glutathione were measured. The results demonstrated that mortality rate, CPK levels, myocardial lipid peroxides, and glutathione levels were decreased in the omega-3 PUFA treated group. Maximum increase in parameters indicative of myocardial damage was seen in the coconut oil group. These findings suggest that dietary omega-3 PUFA offers maximum protection in experimentally induced MI in comparison to omega-6 PUFA and SFA enriched diets. SFA was found to have the least protective effect.     

Rearing system and oleic acid supplementation effect on carcass and lipid characteristics of two muscles from an obese pig breed

Quality of pork depends on genotype, rearing and pre- and post-slaughter conditions. However, no information is available on rearing system changes and oleic acid supplementation on carcass characteristics and fatty acid (FA) profile of pork from the Alentejano (AL) pig, an obese breed. This study evaluates the effects of feeding low (LO) or high oleic acid diets (HO) to AL pigs reared in individual pens (IND) or outdoor (OUT) with access to pasture. Carcass composition was obtained and longissimus dorsi and semimembranosus samples were collected to analyse chemical composition and neutral and polar intramuscular lipids FA profile by gas chromatography. Statistical analysis was performed by a two-way ANOVA for rearing system and diet effects. OUT-reared pigs presented leaner carcasses than IND-reared ones. Both muscles presented lower intramuscular lipid content in OUT-reared pigs. Treatments affected the FA profile of muscles. Overall, OUT-reared pigs presented lower n-6/n-3 FA ratios, whereas pigs fed the HO diet exhibited lower saturated fatty acids (SFA), higher monounsaturated fatty acids (MUFA) levels and lower thrombogenic indexes on neutral intramuscular lipids than LO-fed pigs. On the polar fraction, OUT-reared pigs presented lower SAT and n-6/n-3 FA ratio, and higher polyunsaturated fatty acids (PUFA) levels on both muscles. Pigs fed the HO diet exhibited higher MUFA and lower PUFA levels on both muscles, and lower SAT levels on semimembranosus. This study shows rearing system and oleic acid supplementation have complementary effects and influence carcass composition and the nutritional quality of meat.     

The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases

Several sources of information suggest that human beings evolved on a diet with a ratio of omega-6 to omega-3 essential fatty acids (EFA) of approximately 1 whereas in Western diets the ratio is 15/1-16.7/1. Western diets are deficient in omega-3 fatty acids, and have excessive amounts of omega-6 fatty acids compared with the diet on which human beings evolved and their genetic patterns were established. Excessive amounts of omega-6 polyunsaturated fatty acids (PUFA) and a very high omega-6/omega-3 ratio, as is found in today's Western diets, promote the pathogenesis of many diseases, including cardiovascular disease, cancer, and inflammatory and autoimmune diseases, whereas increased levels of omega-3 PUFA (a lower omega-6/omega-3 ratio), exert suppressive effects. In the secondary prevention of cardiovascular disease, a ratio of 4/1 was associated with a 70% decrease in total mortality. A ratio of 2.5/1 reduced rectal cell proliferation in patients with colorectal cancer, whereas a ratio of 4/1 with the same amount of omega-3 PUFA had no effect. The lower omega-6/omega-3 ratio in women with breast cancer was associated with decreased risk. A ratio of 2-3/1 suppressed inflammation in patients with rheumatoid arthritis, and a ratio of 5/1 had a beneficial effect on patients with asthma, whereas a ratio of 10/1 had adverse consequences. These studies indicate that the optimal ratio may vary with the disease under consideration. This is consistent with the fact that chronic diseases are multigenic and multifactorial. Therefore, it is quite possible that the therapeutic dose of omega-3 fatty acids will depend on the degree of severity of disease resulting from the genetic predisposition. A lower ratio of omega-6/omega-3 fatty acids is more desirable in reducing the risk of many of the chronic diseases of high prevalence in Western societies, as well as in the developing countries.     

Omega-3 polyunsaturated fatty acids improve host response in chronic Pseudomonas aeruginosa lung infection in mice

Pseudomonas aeruginosa is a gram-negative bacilli frequently encountered in human pathology. This pathogen is involved in a large number of nosocomial infections and chronic diseases. Herein we investigated the effects of polyunsaturated fatty acids (PUFA) in chronic Pseudomonas aeruginosa lung infection. C57BL/6 mice were fed for 5 wk with specifically designed diets with high contents in either omega-3 (omega-3) or omega-6 PUFA and compared to a control diet. P. aeruginosa included in agarose beads was then instilled intratracheally, and the animals were studied for 7 days. On the 4th day, the mice fed with the omega-3 diet had a higher lean body mass gain and a lower omega-6:omega-3 ratio of fatty acids extracted from the lung tissue compared with the other groups (P < 0.05). The omega-3 group had the lowest mortality. Distal alveolar fluid clearance (DAFC) as well as the inflammatory response and the cellular recruitment were higher in the omega-3 group on the 4th day. The effect on DAFC was independent of alpha-epithelial Na(+) channels (alpha-ENaC), beta-ENaC, and alpha(1)-Na-K-ATPase mRNA expressions, which were not altered by the different diets. In conclusion, a diet enriched in omega-3 PUFA can change lung membrane composition and improve survival in chronic pneumonia. This effect on survival is probably multifactorial involving the increased DAFC capacity as well as the optimization of the initial inflammatory response. This work suggests that a better control of the omega-6/omega-3 PUFA balance may represent an interesting target in the prevention and/or control of P. aeruginosa infection in patients.     

Metabolic fate of saturated and monounsaturated dietary fats: The Mediterranean diet revisited from epidemiological evidence to cellular mechanisms

Increasing evidence indicates favourable effects of the Mediterranean diet, partly associated to its monounsaturated fatty acids (MUFA) content on both obesity and diabetes. However, neither the underlying mechanisms by which the Mediterranean diet exerts its protective effect, nor the interplay with other environmental factors (i.e. physical activity), are fully characterised. In this review, we examined recent data on how the metabolic fate of MUFA and saturated fatty acids (SFA) differs. Because of differential packaging into lipoproteins, hydrolysis of triacylglycerol-rich lipoproteins by lipoprotein lipase and transport into oxidative tissues, MUFA are oxidised more than SFA. This high MUFA oxidation favour lipid oxidation and according to the oxidative balance concept reduces the risk of obesity. It also improves the intra-muscular triacylglycerol turnover, which mitigates the SFA-induced accumulation of diacylglycerol and ceramides, and thus protects the insulin sensitivity and cell viability. Finally, physical activity through its action on the energy turnover differentially regulates the metabolism of SFA and MUFA. The putative combined role of AMP-activated kinase and mitochondrial glycerol-3-phosphate transferase on the intra-muscular partitioning of MUFA and SFA provides new areas of research to better understand the beneficial effects of the Mediterranean diet and physical activity on obesity and diabetes.     

Contrasting cellularity and fatty acid composition in fat depots from Alentejana and Barrosã bovine breeds fed high and low forage diets

During the finishing phase of bovines, large amounts of subcutaneous and visceral fats are deposited leading to production inefficiencies with major impact on meat quality. A better understanding of the cellularity features of the main fat depots could provide strategies for adipose tissue manipulation. This study assessed the effect of feeding diets with distinct forage to concentrate ratios on the cellularity of two fat depots of beef cattle and their implications on the fatty acid profile. Thus, two phylogenetically distant Portuguese bovine breeds, Alentejana and Barrosã, were selected. The results did not show differences in subcutaneous fat deposition nor in visceral fat depots partitioning. Plasma adipokines concentration failed to show a consistent relationship with fatness, as leptin remained constant in all experimental groups, whereas interleukin-6 was influenced by breed. Fat depot seems to determine the area and number of adipocytes, with larger adipocytes and a lower number of cells in subcutaneous fat than in mesenteric fat. Neither breed nor diet influenced adipocytes area and number. The contents of total fatty acids, partial sums of fatty acids and conjugated linoleic acid isomeric profile were affected by breed and fat depot. The incorporation of saturated fatty acids (SFA), trans fatty acids, polyunsaturated fatty acids (PUFA) and branched chain fatty acids (BCFA) was higher in mesenteric fat depot, whereas subcutaneous fat depot had greater percentages of monounsaturated fatty acids (MUFA). In addition, SFA and MUFA proportions seem to be breed-related. In spite of the less relevant role of diet, the percentages of PUFA and BCFA were influenced by this factor. Under these experimental conditions, the effect of fat depot on cellularity and fatty acid composition prevails over breed or diet, as reinforced by the principal component analysis.     

Fatty acid composition of membrane bilayers: Importance of diet polyunsaturated fat balance

In one of the most extensive analyses to date we show that the balance of diet n-3 and n-6 polyunsaturated fatty acids (PUFA) is the most important determinant of membrane composition in the rat under 'normal' conditions. Young adult male Sprague-Dawley rats were fed one of twelve moderate-fat diets (25% of total energy) for 8weeks. Diets differed only in fatty acid (FA) profiles, with saturate (SFA) content ranging 8-88% of total FAs, monounsaturate (MUFA) 6-65%, total PUFA 4-81%, n-6 PUFA 3-70% and n-3 PUFA 1-70%. Diet PUFA included only essential FAs 18:2n-6 and 18:3n-3. Balance between n-3 and n-6 PUFA is defined as the PUFA balance (n-3 PUFA as % of total PUFA) and ranged 1-86% in the diets. FA composition was measured for brain, heart, liver, skeletal muscle, erythrocytes and plasma phospholipids, as well as adipose tissue and plasma triglycerides. The conformer-regulator model was used (slope=1 indicates membrane composition completely conforming to diet). Extensive changes in diet SFA, MUFA and PUFA had minimal effect on membranes (average slopes 0.01, 0.07, 0.07 respectively), but considerable influence on adipose tissue and plasma triglycerides (average slopes 0.27, 0.53, 0.47 respectively). Diet balance between n-3 and n-6 PUFA had a biphasic influence on membrane composition. When n-3 PUFA<10% of total PUFA, membrane composition completely conformed to diet (average slope 0.95), while diet PUFA balance>10% had little influence (average slope 0.19). The modern human diet has an average PUFA balance ~10% and this will likely have significant health implications.     

Genetic correlation estimates between beef fatty acid profile with meat and carcass traits in Nellore cattle finished in feedlot

The objective of this study was to estimate the genetic–quantitative relationships between the beef fatty acid profile with the carcass and meat traits of Nellore cattle. A total of 1826 bulls finished in feedlot conditions and slaughtered at 24 months of age on average were used. The following carcass and meat traits were analysed: subcutaneous fat thickness (BF), shear force (SF) and total intramuscular fat (IMF). The fatty acid (FA) profile of the Longissimus thoracis samples was determined. Twenty-five FAs (18 individuals and seven groups of FAs) were selected due to their importance for human health. The animals were genotyped with the BovineHD BeadChip and, after quality control for single nucleotide polymorphisms (SNPs), only 470,007 SNPs from 1556 samples remained. The model included the random genetic additive direct effect, the fixed effect of the contemporary group and the animal’s slaughter age as a covariable. The (co)variances and genetic parameters were estimated using the REML method, considering an animal model (single-step GBLUP). A total of 25 multi-trait analyses, with four traits, were performed considering SF, BF and IMF plus each individual FA. The heritability estimates for individual saturated fatty acids (SFA) varied from 0.06 to 0.65, for monounsaturated fatty acids (MUFA) it varied from 0.02 to 0.14 and for polyunsaturated fatty acids (PUFA) it ranged from 0.05 to 0.68. The heritability estimates for Omega 3, Omega 6, SFA, MUFA and PUFA sum were low to moderate, varying from 0.09 to 0.20. The carcass and meat traits, SF (0.06) and IMF (0.07), had low heritability estimates, while BF (0.17) was moderate. The genetic correlation estimates between SFA sum, MUFA sum and PUFA sum with BF were 0.04, 0.64 and ?0.41, respectively. The genetic correlation estimates between SFA sum, MUFA sum and PUFA sum with SF were 0.29, ?0.06 and ?0.04, respectively. The genetic correlation estimates between SFA sum, MUFA sum and PUFA sum with IMF were 0.24, 0.90 and ?0.67, respectively. The selection to improve meat tenderness in Nellore cattle should not change the fatty acid composition in beef, so it is possible to improve this attribute without affecting the nutritional beef quality in zebu breeds. However, selection for increased deposition of subcutaneous fat thickness and especially the percentage of intramuscular fat should lead to changes in the fat composition, highlighting a genetic antagonism between meat nutritional value and acceptability by the consumer.     

Comparison of fatty acids and some mineral matter profiles of wild and farmed snails,Cornu aspersum Müller, 1774

ABSTRACT

The fatty acid and mineral matter compositions of the visceral mass and pedal mass of wild and farmed Cornu aspersum were compared. The relative fatty acid amounts of the visceral and pedal masses of wild and farmed snails are: polyunsaturated fatty acid (PUFA) > saturated fatty acid (SFA) > monounsaturated fatty acid (MUFA), PUFA?>?SFA?>?MUFA, MUFA?>?PUFA?>?SFA and PUFA?>?MUFA?>?SFA, respectively. Wild snails had a higher concentration of iron and zinc than farmed snails. Selenium was 2.82 times higher in the pedal mass of farmed snails than the pedal mass of wild snails. Ca:P ratios in the visceral mass of wild snails, visceral mass and pedal mass of farmed snails were 1.76:1, 1.12:1 and 3.87:1 respectively. Both wild and farmed snails have high contents of oleic, linoleic, eicosapentaenoic and docosahexaenoic fatty acids and are a good source of minerals. Careful attention should be paid, however, as to which diet will be used during farming because the composition of fatty acid in the snail is affected by diet.     

Fatty acid composition,cholesterol and fat‐soluble vitamins of wild‐caught freshwater spiny eel,Mastacembelus simack (Walbaum, 1792)

Because of its local commercial value, the proximate nutritional composition, fatty acid composition, cholesterol and fat‐soluble vitamins of spiny eel (Mastacembelus simack Walbaum, 1792) were determined in 20 specimens caught in Keban Dam Lake, Elaz??, Turkey in September 2009. Moisture, protein, lipid, ash and cholesterol contents of the spiny eel were 75.9, 17.1, 10.9, 1.0% and 52.6 mg per 100 g, respectively. Fatty acid composition showed that total polyunsaturated fatty acids (PUFA) were the highest (37.1%), followed by monounsaturated fatty acids (MUFA, 35.5%) and saturated fatty acids (SFA, 27.4%). The relation between PUFA and SFA (1.35) was comparable to that of some fish species, and PUFA : MUFA : SFA ratio (1.35 : 1.29 : 1) was very close to that recommended by nutritionists. Among the vitamins (A, D, E and K) analyzed, the vitamin E content was highest followed by D, K and A. In conclusion, M. simack is rich in proteins, unsaturated fatty acids and vitamins and low in cholesterol, with a reasonable PUFA : SFA and PUFA : MUFA : SFA ratio as recommended by nutritionists. M. simack can therefore be recommended for human consumption as a good source of nutrition.     

Effects of conjugated linoleic acid or betaine on the growth performance and fatty acid composition in backfat and belly fat of finishing pigs fed dried distillers grains with solubles

The objectives of this study were to determine the effects of conjugated linoleic acid (CLA) or betaine on the growth performance, carcass characteristics and fatty acid composition in backfat and belly fat of pigs fed distillers dried grains with solubles (DDGS). Thirty-two (60±2 kg) crossbred barrows (Duroc×Landrace×Yorkshine) were assigned to one of four diets randomly: (1) the control diet containing no corn DDGS (control group); (2) the diet containing 30% corn DDGS (DDGS-fed group); (3) the diet containing 30% corn DDGS and 10 g/kg CLA (CLA-fed group); (4) the diet containing 30% corn DDGS and 1 g/kg BET (BET-fed group). The pigs fed DDGS showed that the percentages of C18:2, polyunsaturated fatty acid (PUFA) and iodine value (IV) increased, while C18:1, saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) decreased. Pigs fed the DDGS+CLA or DDGS+betaine diets showed the increased percentage of SFA, and the decreased percentage of C18:2, PUFA and IV. In conclusion, results confirmed that the diets containing 30% DDGS had no detrimental effects on growth performance, but increased the percentage of PUFA and IV and decreased the percentage of SFA and MUFA in the backfat and belly fat. However, supplementation with CLA or BET can part reverse these effects on carcass fat in finishing pigs.     

Oil and Seed Meal Quality Indices of Indian Rapeseed-Mustard Varieties

Variation in oil, protein, fatty acid profile, oil stability index, PUFA to SFA, MUFA to PUFA, ω-6 to ω-3 fatty acid ratio and glucosinolate content and their relationships were studied in 50 rapeseed-mustard (Brassica species) varieties. Variability was low for protein and oil content with CV 4.2% and 5.1%, respectively. The highest variation was recorded for oil stability index followed by oleic acid content. Erucic acid ranged from 0.4 % [TERI (00) R- 9903] to 55.3% (NDYS-2). The saturated fatty acids showed a range of 2.5–8.6% and most of the varieties had < 6 %.The maximum (3.05) and minimum (0. 59) ω-6 to ω-3 fatty acid ratio was recorded for TERI (00) R-9903 a variety of gobhi sarson and RTM-314 of taramira, respectively. The highest MUFA to PUFA ratio (3.19) was recorded for variety Parbati of toria. Twelve varieties had PUFA to SFA ratio of > 10.0. All the varieties, in general had high glucosinolate content except GSC- 5, TERI (OE) R-03 and TERI (00) R-9903. Oil stability index had highly significant and positive correlation with oleic acid and MUFA to PUFA ratio. The relationship of oil content was significantly positive with ω-6 to ω-3 fatty acid ratio (r = 0.377**). Protein content and SFA were positively correlated (r = 0.314 *). Erucic acid exhibited negative and significant association with SFA (r = ? 0.293*) and oleic acid (r = ? 0.863**).     

Spatial and temporal variation of the fatty acid composition of Patella spp. (Gastropoda: Prosobranchia) soft bodies and gonads

This study evaluated the effects of season and spatial distribution on the fatty acid composition of Patella depressa gonads and Patella spp. soft body tissue. The results show that the quantitatively most important fatty acids were the saturated fatty acids (SFA) 16:0, 14:0 and 18:0; the monounsaturated fatty acids (MUFA) 18:1(n-7), 18:1(n-9), 16:1(n-7) and 20:1(n-9) and the polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA 20:5(n-3)), and arachidonic acid (ARA 20:4(n-6)). P. depressa and P. ulyssiponensis soft body fatty acid profiles revealed significant differences between sexes; males showed significantly higher percentages of PUFA, highly unsaturated fatty acids (HUFA), (n-3) fatty acids and ARA, while in females significantly higher proportions of MUFA were found. Analysis of variance on the fatty acid composition of P. depressa gonads revealed significant differences between sexes, which were more marked than when the whole body was analysed. Males showed a significantly higher percentage of PUFA, HUFA, fatty acids from the (n-3) and (n-6) series, ARA and EPA, while females were seen to have higher proportions of SFA, MUFA and total fatty acid methyl esters (FAME). Some variability was seen to occur due to shore location and seasons, but these effects were not so obvious.     

Effects of boiling,deep‐frying,and microwave treatment on the proximate composition of rainbow trout fillets: changes in fatty acids,total protein,and minerals

This study was conducted to investigate the differences in the proximate composition (moisture, fat, protein and ash), cholesterol content, energy, mineral composition (Na, Ca, Mg, K, P, Fe and Zn) and fatty acid profile of rainbow trout, Oncorhynchus mykiss, after frying, boiling, or microwaving. Results showed that all cooking methods reduced moisture and increased total protein, fat and ash contents. Also all minerals increased significantly during the microwave and frying methods. Statistical results showed that the major fatty acids among the saturated and monounsaturated fatty acids in each fish were palmitic (C16:0) and oleic (C18:1) acids, respectively. In addition, linoleic acid (C18:2) was predominant in the n‐6 polyunsaturated fatty acids (PUFA) in both cooked and raw trout. The EPA (eicosapentaenoic acid; C20:5 ω3) and DHA (docosahexaenoic acid; C22:6 ω6) acids were the major fatty acids among total n‐3 acids in fish samples. The fatty acids profile of the cooked fish showed a saturated (SFA) and monounsaturated (MUFA) decrease and an increase in PUFA contents. However, the ω‐3 fatty acids content increased in microwaved samples but decreased in the fried samples. Moreover, the PUFA/SFA and Hypocholesterolaemic/Hypercholesterolaemic (HH) ratios increased in both fried and microwaved trout, whereas significant increases in ω3/ω6 as well as EPA + DHA/C16 content were observed only in microwaved samples. A significant increase in energy content was observed in all cooked samples, whereas the cholesterol decreased. Research results show that microwaving is recommended as the best cooking method for a healthy consumption of rainbow trout.     

Acute ingestion of different dietary fatty acid species modulates postprandial lipid responses in New Zealand white rabbits

Although several investigations have linked the degree of fatty acid saturation to plasma lipid responses in the postprandial state, further evaluation is necessary. In this study, we compared the effect of saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids on postprandial lipid metabolism using complementary in vivo and in vitro approaches. Fat (10 g) cholesterol (0.5 g) test meals that provided either lard (SFA), olive oil (MUFA), or sunflower oil (PUFA) were ingested by chow-fed New Zealand white rabbits (n = 8). In addition, hepatic uptake of triglyceride-cholesterol-rich lipoproteins (TCRL) isolated from rabbits chronically ingesting SFA, MUFA, or PUFA diets was measured using freshly isolated chow-fed rabbit hepatocytes. Whatever dietary fatty acids ingested, postprandial triglyceridemia and occurrence of radiolabelled dietary lipids in plasma were not markedly different. Conversely, SFA induced higher postprandial cholesterolemia and phospholipemia than MUFA (P < 0.05) whereas PUFA prevented postprandial cholesterol increase. TCRL disappearance from cultured liver cell media was delayed with SFA-rich TCRL and faster with PUFA whereas MUFA-rich TCRL showed an intermediate figure. From these data, we conclude that SFA, MUFA, and PUFA elicited different postprandial plasma and lipoprotein lipid responses. The fatty acid composition of TCRL had a major impact on their subsequent metabolism, especially uptake by cultured hepatocytes. The SFA-induced hypercholesterolemia could be related to an altered hepatic uptake whereas a faster clearance and hepatic uptake could explain the cholesterol-lowering effect of PUFA in rabbits. MUFA, like PUFA, accelerate uptake by hepatocytes but favor cholesterol ester enrichment of TCRL.     

Effect of weight at slaughter and breed on beef intramuscular lipid classes and fatty acid profile

The effect of slaughter weight and breed on the composition of intramuscular fat (IMF) of seven Spanish cattle breeds was studied. Lipid classes and fatty acids were evaluated in young bulls of seven local Spanish cattle breeds, Asturiana, Avileña, Morucha, Parda Alpina, Pirenaica, Retinta and Rubia Gallega, slaughtered at a live weight of 320 kg (veal type) and 550 kg (yearling bull type). Higher slaughter weight and early maturating breeds produced higher IMF content in the longissimus muscle (P < 0.001), which was linked to a reduction in phospholipids, monoglycerides, diglycerides, cholesterol and free-fatty acids content, but an increase in triacylglycerols. Besides, heavier animals displayed a higher percentage of saturated and monounsaturated fatty acids (MUFA), but a lower polyunsaturated fatty acids (PUFA) percentage (P < 0.001). The increase in triglycerides (TG), saturated fatty acids (SFA) and MUFA illustrates the increasing importance of lipid storage as fattening proceeds and the acquisition of ruminal functionality. The feeding system based on cereals had a strong influence on the fatty acid profile, giving the studied beef a relatively high PUFA/SFA and n-6/n-3 ratios.     

A Metabolomic Analysis of Omega-3 Fatty Acid-Mediated Attenuation of Western Diet-Induced Nonalcoholic Steatohepatitis in LDLR -/- Mice

Background

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease and a risk factor for cirrhosis, hepatocellular carcinoma and liver failure. Previously, we reported that dietary docosahexaenoic acid (DHA, 22:6,n-3) was more effective than eicosapentaenoic acid (EPA, 20:5,n-3) at reversing western diet (WD) induced NASH in LDLR^-/- mice.

Methods

Using livers from our previous study, we carried out a global non-targeted metabolomic approach to quantify diet-induced changes in hepatic metabolism.

Results

Livers from WD + olive oil (WD + O)-fed mice displayed histological and gene expression features consistent with NASH. The metabolomic analysis of 320 metabolites established that the WD and n-3 polyunsaturated fatty acid (PUFA) supplementation had broad effects on all major metabolic pathways. Livers from WD + O-fed mice were enriched in saturated (SFA) and monounsaturated fatty acids (MUFA), palmitoyl-sphingomyelin, cholesterol, n-6 PUFA, n-6 PUFA-containing phosphoglycerolipids, n-6 PUFA-derived oxidized lipids (12-HETE) and depleted of C_20-22 n-3 PUFA-containing phosphoglycerolipids, C_20-22 n-3 PUFA-derived oxidized lipids (18-HEPE, 17,18-DiHETE) and S-lactoylglutathione, a methylglyoxal detoxification product. WD + DHA was more effective than WD + EPA at attenuating WD + O-induced changes in NASH gene expression markers, n-6 PUFA and oxidized lipids, citrate and S-lactosyl glutathione. Diet-induced changes in hepatic MUFA and sphingolipid content were associated with changes in expression of enzymes involved in MUFA and sphingolipid synthesis. Changes in hepatic oxidized fatty acids and S-lactoylglutathione, however, correlated with hepatic n-3 and n-6 C_20-22 PUFA content. Hepatic C_20-22 n-3 PUFA content was inversely associated with hepatic α-tocopherol and ascorbate content and positively associated with urinary F2- and F3-isoprostanes, revealing diet effects on whole body oxidative stress.

Conclusion

DHA regulation of hepatic SFA, MUFA, PUFA, sphingomyelin, PUFA-derived oxidized lipids and S-lactoylglutathione may explain the protective effects of DHA against WD-induced NASH in LDLR^-/- mice.     

Effect of sex,dietary glycerol or dietary fat during late fattening,on fatty acid composition and positional distribution of fatty acids within the triglyceride in pigs

The effect of sex, source of saturated fat (lard v. palm oil) and glycerol inclusion in the fattening diet on composition and fatty acid positional distribution in the triglyceride molecule was studied in pigs from 78 to 110 kg BW. Average daily gain and carcass characteristics, including ham and loin weight, were not affected by dietary treatment but sex affected backfat depth (P<0.01). A significant interaction between sex and glycerol inclusion was observed; dietary glycerol increased lean content in gilts but not in barrows (P<0.05 for the interaction). Individual and total saturated fatty acid (SFA) concentrations were greater in barrows than in gilts. In contrast, the concentration of total polyunsaturated fatty acids (PUFA) and of C18:2n-6, C18:3n-3, C20:3n-9 and C20:4n-6 in the intramuscular fat (IMF) was higher (P<0.05) in gilts than in barrows. Sex did not affect total monounsaturated fatty acids (MUFA) concentration in the IMF. The proportion of SFA in the subcutaneous fat (SF) was higher in barrows than in gilts (P<0.001). Within the individual SFA, sex affected only the concentrations of C14:0 and C16:0 (P<0.001). Dietary fat did not affect total SFA or PUFA concentrations of the IMF but the subcutaneous total MUFA concentration tended to be higher (P=0.079) in pigs fed lard than in pigs fed palm oil. Dietary glycerol increased total MUFA and C18:1n-9 concentration in the IMF and increased total MUFA and decreased C18:2n-6, C18:3n-3 and total PUFA concentrations in the SF. The data indicate that altering the fatty acid composition of the triglyceride molecule at the 2-position, by dietary intervention during the fattening phase, is very limited.     

Different fatty acid composition in central and peripheral adipose tissues of the American mink (Mustela vison)

Fatty acid (FA) composition in the intraabdominal (IAB), subcutaneous (SC) and peripheral adipose tissues of the semiaquatic American mink (Mustela vison) was examined in comparison to the diet by gas-liquid chromatography. There was a clear compositional gradient from the IAB via SC to peripheral adipose tissues and the anatomically different adipose tissues accumulated or metabolized FA selectively. The total lipids of the body appendages had smaller proportions of saturated (SFA) and larger proportions of monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) than the lipids of the trunk adipose tissues. Especially n-3 PUFA were enriched in the periphery. The appendages were also characterized with a high ratio of unsaturated FA to SFA, an increased Delta9-desaturation index and increased mean numbers of double bonds and carbon atoms in a FA molecule. The proportions of SFA and MUFA of the diet resembled the trunk adipose tissues while the dietary percentage of n-3 PUFA surpassed those of the trunk fat depots but was lower than those of the peripheral fats. These data confirm that the FA signatures of mammals reflect not only their dietary history but also metabolic modifications of ingested FA.     

Reduction of inflammation and chronic tissue damage by omega-3 fatty acids in fat-1 transgenic mice with pancreatitis

Pancreatitis is a severe debilitating disease with high morbidity and mortality. Treatment is mostly supportive, and until now there are no clinically useful strategies for anti-inflammatory therapy. Although omega-3 polyunsaturated fatty acids (n-3 PUFA) are known to have anti-inflammatory effects, the utility of these fatty acids in the alleviation of pancreatitis remained to be investigated. The aim of this study was to examine the effect of n-3 PUFA on both acute and chronic pancreatitis in a well-controlled experimental system. We used the fat-1 transgenic mouse model, characterized by endogenously increased tissue levels of n-3 PUFA, and their wild-type littermates to examine the effect of n-3 PUFA on both acute and chronic cerulein-induced pancreatitis. Disease activity and inflammatory status were assessed by both histology and molecular methods. In acute pancreatitis, fat-1 mice showed a trend towards decreased necrosis and significantly reduced levels of plasma IL-6 levels as well as reduced neutrophil infiltration in the lung. In chronic pancreatitis there was less pancreatic fibrosis and collagen content accompanied by decreased pancreatic stellate cell activation in the fat-1 animals with increased n-3 PUFA tissue levels as compared to wild-type littermates with high levels of omega-6 (n-6) PUFA in their tissues. Our data provide evidence for a reduction of systemic inflammation in acute pancreatitis and of tissue fibrosis in chronic pancreatitis by increasing the tissue content of omega-3 polyunsaturated fatty acids. These results suggest a beneficial potential for n-3 PUFA supplementation in acute and particularly chronic pancreatitis.