Refined mackerel oil increases hepatic lipid accumulation and reduces choline and choline-containing metabolites in the liver tissue in mice fed a Western diet.

In this study, we aimed to evaluate the impact of consuming refined mackerel oil (MO) from rest raw material on hepatic fat accumulation, glucose tolerance, and metabolomic changes in the liver from male C57BL/6N mice. The mice were fed either a Western diet (WD) or a chow diet, with 30 g or 60 g MO per kg of diet (3% or 6%) for 13 weeks. Body weight, energy intake, and feed efficiency were monitored throughout the experiment. A glucose tolerance test was conducted after 11 weeks, and metabolomic analyses of the liver were performed at termination. Inclusion of MO in the WD, but not in the chow diet, led to increased liver weight, hepatic lipid accumulation, elevated fasting blood glucose, reduced glucose tolerance, and insulin sensitivity. Hepatic levels of eicosapentaenoic and docosahexaenoic acid increased, but no changes in levels of saturated and monounsaturated fatty acids were observed. The liver metabolomic profile was different between mice fed a WD with or without MO, with a reduction in choline ether lipids, phosphatidylcholines, and sphingomyelins in mice fed MO. This study demonstrates that supplementing the WD, but not the chow diet, with refined MO accelerates accumulation of hepatic fat droplets and negatively affects blood glucose regulation. The detrimental effects of supplementing a WD with MO were accompanied by increased fat digestibility and overall energy intake, and lower levels of choline and choline-containing metabolites in liver tissue.

Metabolic effects of diet containing blue mussel (Mytilus edulis) and blue mussel-fed salmon in a mouse model of obesity.

Alternative feed ingredients for farmed salmon are warranted due to increasing pressure on wild fish stocks. As locally farmed blue mussels may represent an environmentally sustainable substitute with a lower carbon footprint, we aimed to test the potential and safety of substituting fish meal with blue mussel meal in feed for Atlantic salmon. Salmon were fed diets in which fish meal was partially replaced with blue mussel meal in increments, accounting for up to 13.1 % of the ingredients. Fillets from the salmon were subsequently used to prepare obesity-promoting western diets for a 13-weeks mouse feeding trial. In a second mouse trial, we tested the effects of inclusion of up to 8% blue mussel meal directly in a meat-based western diet. Partial replacement of fish meal with blue mussel meal in fish feed preserved the n-3 polyunsaturated fatty acid (PUFA) content in salmon fillets. The observed blue mussel-induced changes in the fatty acid profiles in salmon fillets did not translate into similar changes in the livers of mice that consumed the salmon, and no clear dose-dependent responses were found. The relative levels of the marine n-3 fatty acids, EPA, and DHA were not reduced, and the n-3/n-6 PUFA ratios in livers from all salmon-fed mice were unchanged. The inclusion of blue mussel meal in a meat-based western diet led to a small, but dose-dependent increase in the n-3/n-6 PUFA ratios in mice livers. Diet-induced obesity, glucose intolerance, and hepatic steatosis were unaffected in both mice trials and no blue mussel-induced adverse effects were observed. In conclusion, our results suggest that replacing fish meal with blue mussel meal in salmon feed will not cause adverse effects in those who consume the salmon fillets.

Dietary Selenomethionine Reduce Mercury Tissue Levels and Modulate Methylmercury Induced Proteomic and Transcriptomic Alterations in Hippocampi of Adolescent BALB/c Mice.

Methylmercury (MeHg) is a well-known environmental contaminant, particularly harmful to the developing brain. The main human dietary exposure to MeHg occurs through seafood consumption. However, seafood also contains several nutrients, including selenium, which has been shown to interact with MeHg and potentially ameliorate its toxicity. The aim of this study was to investigate the combined effects of selenium (as selenomethionine; SeMet) and MeHg on mercury accumulation in tissues and the effects concomitant dietary exposure of these compounds exert on the hippocampal proteome and transcriptome in mice. Adolescent male BALB/c mice were exposed to SeMet and two different doses of MeHg through their diet for 11 weeks. Organs, including the brain, were sampled for mercury analyses. Hippocampi were collected and analyzed using proteomics and transcriptomics followed by multi-omics bioinformatics data analysis. The dietary presence of SeMet reduced the amount of mercury in several organs, including the brain. Proteomic and RNA-seq analyses showed that both protein and RNA expression patterns were inversely regulated in mice receiving SeMet together with MeHg compared to MeHg alone. Several pathways, proteins and RNA transcripts involved in conditions such as immune responses and inflammation, oxidative stress, cell plasticity and Alzheimer's disease were affected inversely by SeMet and MeHg, indicating that SeMet can ameliorate several toxic effects of MeHg in mice.

Commercially available kelp and seaweed products - valuable iodine source or risk of excess intake?

BACKGROUND: Seaweeds and kelps, also known as macroalgae, have long been common in the East-Asian diet. During recent years, macroalgae have entered the global food market, and a variety of macroalgae products are now available for consumers. Some macroalgae species are known to be particularly rich in iodine, but little data regarding the iodine content of macroalgae-containing foods exists. OBJECTIVE: The aim of this research study was to analyse the iodine content in a large variety of commercially available macroalgae-containing foods and supplements and to evaluate whether such products are sources of adequate dietary iodine. DESIGN: Ninety-six different products were collected after surveying the Norwegian market for commercially available macroalgae products, collected from three categories: 1) wholefood macroalgae products (n = 43), 2) macroalgae-containing foods (n = 39), and 3) dietary supplements containing macroalgae (n = 14). All products were analysed for iodine content by inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: The iodine content in one portion of wholefood macroalgae products ranged from 128 to 62,400 µg. In macroalgae-containing foods, the iodine content ranged from 30 to 25,300 µg per portion, and in supplements it ranged from 5 to 5,600 µg per daily dose. The species with the highest analysed iodine content were oarweed, sugarkelp and kombu, with mean iodine levels of 7,800, 4,469 and 2,276 µg/g, respectively. For 54 products, the intake of one portion or dose would exceed the tolerable upper intake level (UL) for iodine. DISCUSSION AND CONCLUSION: The iodine content in the included products was variable and for most products high, exceeding the tolerable upper intake level (UL) if consumed as a serving or portion size. The labelling of macroalgae species included, and declaration of iodine content, were inadequate or inaccurate for several products. As macroalgae-containing products are unreliable iodine sources, inclusion of such products in the diet may pose a risk of consuming excessive amounts of iodine.

Lean-seafood intake increases urinary iodine concentrations and plasma selenium levels: a randomized controlled trial with crossover design.

PURPOSE: Iodine deficiency due to insufficient nutritional intake is a public health challenge in several European countries, including Norway. Lean-seafood has a high iodine and arsenic (As) content and is a good source of selenium (Se). Evidence of a direct effect of increased intake of lean-seafood on iodine status is limited. The main aims were to determine the iodine status at baseline and to investigate possible dietary effects on urinary iodine concentration (UIC) after intervention with lean-seafood versus non-seafood. Plasma Se, and plasma and urinary As concentrations were also measured. METHODS: A randomized controlled crossover study comprising two 4 weeks experimental periods with two balanced diets varied in main proteins (60% of total dietary proteins) of lean-seafood and non-seafood, separated by a 5 week washout period. RESULTS: Twenty participants (7 males, 13 females) were included and the mean ± SD age was 50.6 ± 15.3 years for all participants. Fasting UIC was median (25th, 75th percentile) 70 (38, 110) and 79 (49, 94) µg/L in the lean-seafood and non-seafood intervention at baseline, respectively. UIC increased after 4 weeks of the lean-seafood intervention to 135 (110, 278) µg/L, but not after the non-seafood intervention [58 (33, 91) µg/L] (P diet-effect < 0.001). Fasting plasma Se increased in the lean-seafood intervention and decreased in the non-seafood intervention (P diet-effect = 0.001). Fasting urinary and plasma As increased in the lean-seafood intervention and was unchanged in the non-seafood intervention (P diet-effect < 0.001). CONCLUSION: The participant's UIC was below the recommended median (100 µg/L) at baseline, but increased sufficiently after a 4 week intervention with lean-seafood.

Seafood intake and the development of obesity, insulin resistance and type 2 diabetes.

We provide an overview of studies on seafood intake in relation to obesity, insulin resistance and type 2 diabetes. Overweight and obesity development is for most individuals the result of years of positive energy balance. Evidence from intervention trials and animal studies suggests that frequent intake of lean seafood, as compared with intake of terrestrial meats, reduces energy intake by 4-9 %, sufficient to prevent a positive energy balance and obesity. At equal energy intake, lean seafood reduces fasting and postprandial risk markers of insulin resistance, and improves insulin sensitivity in insulin-resistant adults. Energy restriction combined with intake of lean and fatty seafood seems to increase weight loss. Marine n-3 PUFA are probably of importance through n-3 PUFA-derived lipid mediators such as endocannabinoids and oxylipins, but other constituents of seafood such as the fish protein per se, trace elements or vitamins also seem to play a largely neglected role. A high intake of fatty seafood increases circulating levels of the insulin-sensitising hormone adiponectin. As compared with a high meat intake, high intake of seafood has been reported to reduce plasma levels of the hepatic acute-phase protein C-reactive protein level in some, but not all studies. More studies are needed to confirm the dietary effects on energy intake, obesity and insulin resistance. Future studies should be designed to elucidate the potential contribution of trace elements, vitamins and undesirables present in seafood, and we argue that stratification into responders and non-responders in randomised controlled trials may improve the understanding of health effects from intake of seafood.

Mechanisms Preserving Insulin Action during High Dietary Fat Intake.

Prolonged intervention studies investigating molecular metabolism are necessary for a deeper understanding of dietary effects on health. Here we provide mechanistic information about metabolic adaptation to fat-rich diets. Healthy, slightly overweight men ingested saturated or polyunsaturated fat-rich diets for 6 weeks during weight maintenance. Hyperinsulinemic clamps combined with leg balance technique revealed unchanged peripheral insulin sensitivity, independent of fatty acid type. Both diets increased fat oxidation potential in muscle. Hepatic insulin clearance increased, while glucose production, de novo lipogenesis, and plasma triacylglycerol decreased. High fat intake changed the plasma proteome in the immune-supporting direction and the gut microbiome displayed changes at taxonomical and functional level with polyunsaturated fatty acid (PUFA). In mice, eucaloric feeding of human PUFA and saturated fatty acid diets lowered hepatic triacylglycerol content compared with low-fat-fed control mice, and induced adaptations in the liver supportive of decreased gluconeogenesis and lipogenesis. Intake of fat-rich diets thus induces extensive metabolic adaptations enabling disposition of dietary fat without metabolic complications.

Effects of geography and species variation on selenium and mercury molar ratios in Northeast Atlantic marine fish communities.

Methylmercury (MeHg) is a potent neurotoxin that bioaccumulates in seafood. Co-occurrence of selenium (Se) may affect the bioavailability and toxicity of MeHg in organisms. Here we report the concentrations of total mercury (Hg) and Se in 17 teleost fish species (n = 8459) sampled during 2006-2015 from the North East Atlantic Ocean (NEAO) and evaluate species variation and effects of geography. Mean Hg concentration ranged from 0.04 mg kg-1 ww in Atlantic mackerel (Scomber scombrus) and blue whiting (Micromesistius poutassou) to 0.72 mg kg-1 ww in blue ling (Molva dypterygia). Se concentrations were less variable and ranged from 0.27 mg kg-1 ww in Atlantic cod (Gadus morhua) to 0.56 mg kg-1 ww in redfish (Sebastes spp.). The mean Se:Hg molar ratio ranged from 1.9 in blue ling to 43.3 in mackerel. Pelagic species had the lowest Hg concentrations and the highest Se:Hg ratios, whereas demersal species had the highest Hg concentrations and the lowest Se:Hg ratios. Se and Hg concentrations were positively correlated in 13 of the 17 species. Hg concentrations increased from the North to South in contrast to the Se:Hg molar ratio which exhibited the opposite trend. Fish from fjord and coastal areas had higher concentrations of Hg and lower Se:Hg molar ratios compared to fish sampled offshore. All species had average Se:Hg molar ratios >1 and Hg concentrations were largely below the EU maximum level of 0.5 mg kg-1 ww with few exceptions including the deep water species tusk (Brosme brosme) and blue ling sampled from fjord and coastal habitats. Our results show that two fillet servings of tusk, blue ling or Atlantic halibut (Hippoglossus hippoglossus) exceeded the tolerable weekly intake of MeHg although the surplus Se may possibly ameliorate the toxic effects of MeHg. However, some individuals with selenium deficiencies may exhibit greater sensitivity to MeHg.

Effects of Frozen Storage on Phospholipid Content in Atlantic Cod Fillets and the Influence on Diet-Induced Obesity in Mice.

A large fraction of the n-3 polyunsaturated fatty acids (PUFAs) in cod fillet is present in the form of phospholipids (PLs). Freezing initiates hydrolysis of the PLs present in the fillet. Here, we compared the effects of Western diets based on frozen cod, fresh cod or pork with a diet based on casein in male C57BL/6J mice fed for 12 weeks at thermoneutrality. Diets based on fresh cod contained more PL-bound n-3 PUFAs (3.12 mg/g diet) than diets based on frozen cod (1.9 mg/g diet). Mice fed diets containing pork and fresh cod, but not frozen cod, gained more body and fat mass than casein-fed mice. Additionally, the bioavailability of n-3 PUFAs present in the cod fillets was not influenced by storage conditions. In a second experiment, diets with pork as the protein source were supplemented with n-3 PUFAs in the form of PL or triacylglycerol (TAG) to match the levels of the diet containing fresh cod. Adding PL-bound, but not TAG-bound, n-3 PUFAs, to the pork-based diet increased body and fat mass gain. Thus, supplementation with PL-bound n-3 PUFAs did not protect against, but rather promoted, obesity development in mice fed a pork-based diet.

Analyses of gut microbiota and plasma bile acids enable stratification of patients for antidiabetic treatment.

Antidiabetic medication may modulate the gut microbiota and thereby alter plasma and faecal bile acid (BA) composition, which may improve metabolic health. Here we show that treatment with Acarbose, but not Glipizide, increases the ratio between primary BAs and secondary BAs and plasma levels of unconjugated BAs in treatment-naive type 2 diabetes (T2D) patients, which may beneficially affect metabolism. Acarbose increases the relative abundances of Lactobacillus and Bifidobacterium in the gut microbiota and depletes Bacteroides, thereby changing the relative abundance of microbial genes involved in BA metabolism. Treatment outcomes of Acarbose are dependent on gut microbiota compositions prior to treatment. Compared to patients with a gut microbiota dominated by Prevotella, those with a high abundance of Bacteroides exhibit more changes in plasma BAs and greater improvement in metabolic parameters after Acarbose treatment. Our work highlights the potential for stratification of T2D patients based on their gut microbiota prior to treatment.

High-fat feeding rather than obesity drives taxonomical and functional changes in the gut microbiota in mice.

BACKGROUND: It is well known that the microbiota of high-fat (HF) diet-induced obese mice differs from that of lean mice, but to what extent, this difference reflects the obese state or the diet is unclear. To dissociate changes in the gut microbiota associated with high HF feeding from those associated with obesity, we took advantage of the different susceptibility of C57BL/6JBomTac (BL6) and 129S6/SvEvTac (Sv129) mice to diet-induced obesity and of their different responses to inhibition of cyclooxygenase (COX) activity, where inhibition of COX activity in BL6 mice prevents HF diet-induced obesity, but in Sv129 mice accentuates obesity. RESULTS: Using HiSeq-based whole genome sequencing, we identified taxonomic and functional differences in the gut microbiota of the two mouse strains fed regular low-fat or HF diets with or without supplementation with the COX-inhibitor, indomethacin. HF feeding rather than obesity development led to distinct changes in the gut microbiota. We observed a robust increase in alpha diversity, gene count, abundance of genera known to be butyrate producers, and abundance of genes involved in butyrate production in Sv129 mice compared to BL6 mice fed either a LF or a HF diet. Conversely, the abundance of genes involved in propionate metabolism, associated with increased energy harvest, was higher in BL6 mice than Sv129 mice. CONCLUSIONS: The changes in the composition of the gut microbiota were predominantly driven by high-fat feeding rather than reflecting the obese state of the mice. Differences in the abundance of butyrate and propionate producing bacteria in the gut may at least in part contribute to the observed differences in obesity propensity in Sv129 and BL6 mice.

Dietary intake and adipose tissue content of long-chain n-3 PUFAs and subsequent 5-y change in body weight and waist circumference.

Background: Adding long-chain n-3 (ω-3) polyunsaturated fatty acids (PUFAs) to a rodent diet reduces fat mass and prevents the development of obesity, but evidence of a similar effect in humans is rather limited.Objectives: We investigated the associations between dietary intake and adipose tissue content of long-chain n-3 PUFAs and subsequent 5-y change in body weight and waist circumference in humans. Effect modification by the carbohydrate:protein ratio and glycemic index was also investigated.Design: A total of 29,152 participants included in the Diet, Cancer, and Health cohort were followed. Dietary intake was assessed with the use of a validated 192-item semiquantitative food-frequency questionnaire. Adipose tissue content of fatty acids was determined by gas chromatography in a random sample of the cohort (n = 1660). Anthropometric measurements were taken at baseline and 5 y later. Associations were investigated with the use of a linear regression model.Results: For high (1.22 g/d) compared with low (0.28 g/d) total n-3 PUFA intake, the difference in 5-y weight change was 147.6 g (95% CI: -42.3, 337.5 g); P-trend = 0.088. No associations between the individual n-3 PUFAs eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid were observed. Intake of n-3 PUFAs was not associated with a 5-y change in waist circumference. For high (0.16%) compared with low (0.06%) adipose tissue content of EPA, the difference in 5-y weight change was -649.6 g (95% CI: -1254.2, -44.9 g); P-trend = 0.027. No associations between total n-3 PUFA, docosapentaenoic acid, and docosahexaenoic acid and 5-y weight change were observed. Adipose tissue content of n-3 PUFAs was not associated with 5-y change in waist circumference. No effect modification by carbohydrate:protein ratio or glycemic index was found.Conclusion: Dietary intake and adipose tissue content of long-chain n-3 PUFAs were neither consistently nor appreciably associated with change in body weight or waist circumference.

Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates.

OBJECTIVE: Fibroblast-growth factor 21 (FGF21) is thought to be important in metabolic regulation. Recently, low protein diets have been shown to increase circulating FGF21 levels. However, when energy contribution from dietary protein is lowered, other macronutrients, such as carbohydrates, must be increased to meet eucaloric balance. This raises the possibility that intake of a diet rich in carbohydrates may induce an increase in plasma FGF21 levels per se. Here we studied the role of dietary carbohydrates on the levels of circulating FGF21 and concomitant physiologic effects by feeding healthy men a carbohydrate rich diet without reducing protein intake. METHODS: A diet enriched in carbohydrates (80 E% carbohydrate; CHO) and a eucaloric control diet (CON) were provided to nine healthy men for three days. The energy intake during the CHO diet was increased (+75% energy) to ensure similar dietary protein intake in CHO and CON. To control for the effect of caloric surplus, we similarly overfed (+75% energy) the same subjects for three days with a fat-rich diet (78 E% fat; FAT), consisting of primarily unsaturated fatty acids. The three diets were provided in random order. RESULTS: After CHO, plasma FGF21 concentration increased 8-fold compared to CON (329 ± 99 vs. 39 ± 9 pg ml-1, p < 0.05). In contrast, after FAT only a non-significant tendency (p = 0.073) to an increase in plasma FGF21 concentration was found. The increase in FGF21 concentration after CHO correlated closely (r = 0.88, p < 0.01) with increased leg glucose uptake (62%, p < 0.05) and increased hepatic glucose production (17%, p < 0.01), indicating increased glucose turnover. Plasma fatty acid (FA) concentration was decreased by 68% (p < 0.01), supported by reduced subcutaneous adipose tissue HSL Ser660 phosphorylation (p < 0.01) and perilipin 1 protein content (p < 0.01), pointing to a suppression of adipose tissue lipolysis. Concomitantly, a 146% increase in the plasma marker of hepatic de novo lipogenesis C16:1 n-7 FA (p < 0.01) was observed together with 101% increased plasma TG concentration (p < 0.001) in association with CHO intake and increased plasma FGF21 concentration. CONCLUSION: Excess dietary carbohydrate, but not fat, led to markedly increased FGF21 secretion in humans, notably without protein restriction, and affected glucose and lipid homeostais.

A safflower oil based high-fat/high-sucrose diet modulates the gut microbiota and liver phospholipid profiles associated with early glucose intolerance in the absence of tissue inflammation.

SCOPE: Omega-6 (n-6) PUFA-rich diets are generally considered obesogenic in rodents. Here, we examined how long-term intake of a high-fat/high-sucrose (HF/HS) diet based on safflower oil affected metabolism, inflammation, and gut microbiota composition. METHODS AND RESULTS: We fed male C57BL/6J mice a HF/HS diet based on safflower oil-rich in n-6 PUFAs-or a low-fat/low-sucrose diet for 40 wk. Compared to the low-fat/low-sucrose diet, intake of the safflower-based HF/HS diet only led to moderate weight gain, while glucose intolerance developed at week 5 prior to signs of inflammation, but concurrent with increased levels of linoleic acid and arachidonic acid in hepatic phospholipids. Intake of the HF/HS diet resulted in early changes in the gut microbiota, including an increased abundance of Blautia, while late changes coincided with altered inflammatory profiles and increased fasting plasma insulin. Analysis of immune cells in visceral fat and liver revealed no differences between diets before week 40, where the number of immune cells decreased in the liver of HF/HS-fed mice. CONCLUSION: We suggest that a diet-dependent increase in the n-6 to omega-3 (n-3) PUFA ratio in hepatic phospholipids together with gut microbiota changes contributed to early development of glucose intolerance without signs of inflammation.

FFAR4 (GPR120) Signaling Is Not Required for Anti-Inflammatory and Insulin-Sensitizing Effects of Omega-3 Fatty Acids.

Free fatty acid receptor-4 (FFAR4), also known as GPR120, has been reported to mediate the beneficial effects of omega-3 polyunsaturated fatty acids (ω3-PUFAs) by inducing an anti-inflammatory immune response. Thus, activation of FFAR4 has been reported to ameliorate chronic low-grade inflammation and insulin resistance accompanying obesity. However, conflicting reports on the role of FFAR4 in mediating the effects of ω3-PUFAs are emerging, suggesting that FFAR4 may not be the sole effector. Hence analyses of the importance of this receptor in relation to other signaling pathways and prominent effects of ω3-PUFAs remain to be elucidated. In the present study, we used Ffar4 knockouts (KO) and heterozygous (HET) mice fed either low fat, low sucrose reference diet; high fat, high sucrose ω3-PUFA; or high fat, high sucrose ω6-PUFA diet for 36 weeks. We demonstrate that both KO and HET mice fed ω3-PUFAs were protected against obesity, hepatic triacylglycerol accumulation, and whole-body insulin resistance. Moreover, ω3-PUFA fed mice had increased circulating protein levels of the anti-inflammatory adipokine, adiponectin, decreased fasting insulin levels, and decreased mRNA expression of several proinflammatory molecules within visceral adipose tissue. In conclusion, we find that FFAR4 signaling is not required for the reported anti-inflammatory and insulin-sensitizing effects mediated by ω3-PUFAs.

Marine fatty acids aggravate hepatotoxicity of α-HBCD in juvenile female BALB/c mice.

Oily fish, a source of long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs), may contain persistent organic pollutants (POPs), including α-hexabromocyclododecane (α-HBCD). In experimental studies, marine LC n-3 PUFAs ameliorate fatty liver development while HBCD exposure was found to cause liver fatty acid (FA) changes. The present study investigated interactions of FAs and α-HBCD in juvenile female BALB/c mice using a factorial design. Mice (n = 48) were exposed for 28 days to a low (100 µg*kg body weight (BW)-1*day-1) or high dose (100 mg*kg BW-1*day-1) of α-HBCD in diets with or without LC n-3 PUFAs. High dose α-HBCD affected whole body lipid metabolism leading to changes in body weight and composition, and pathological changes in hepatic histology, which surprisingly were aggravated by dietary LC n-3 PUFAs. Hepatic FA profiling and gene expression analysis indicated that the dietary modulation of the hepatotoxic response to the high dose of α-HBCD was associated with differential effects on FA ß-oxidation. Our results suggest that in a juvenile mouse model, marine FAs accentuate hepatotoxic effects of high dose α-HBCD. This highlights that the background diet is a critical variable in the risk assessment of POPs and warrants further investigation of dietary mediated toxicity of food contaminants.

Intake of a Western diet containing cod instead of pork alters fatty acid composition in tissue phospholipids and attenuates obesity and hepatic lipid accumulation in mice.

The content of the marine n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is far lower in lean than in fatty seafood. Cod filets contain less than 2g fat per kg, whereof approximately 50% is EPA and DHA. However, a large fraction of these n-3 PUFAs is present in the phospholipid (PL) fraction and may have high bioavailability and capacity to change the endocannabinoid profile. Here we investigated whether exchanging meat from a lean terrestrial animal with cod in a background Western diet would alter the endocannabinoid tone in mice and thereby attenuate obesity development and hepatic lipid accumulation. Accordingly, we prepared iso-caloric diets with 15.1 energy (e) % protein, 39.1 e% fat and 45.8 e% carbohydrates using freeze-dried meat from cod filets or pork sirloins, and using a combination of soybean oil, corn oil, margarine, milk fat, and lard as the fat source. Compared with mice receiving diets containing pork, mice fed cod gained less adipose tissue mass and had a lower content of hepatic lipids. This was accompanied by a lower n-6 to n-3 ratio in liver PLs and in red blood cells (RBCs) in the mice. Furthermore, mice receiving the cod-containing diet had lower circulating levels of the two major endocannabinoids, N-arachidonoylethanolamine and 2-arachidonoylglycerol. Together, our data demonstrate that despite the relatively low content of n-3 PUFAs in cod fillets, the cod-containing diet could exert beneficial metabolic effects.

Intake of farmed Atlantic salmon fed soybean oil increases hepatic levels of arachidonic acid-derived oxylipins and ceramides in mice.

Introduction of vegetable ingredients in fish feed has affected the fatty acid composition in farmed Atlantic salmon (Salmo salar L). Here we investigated how changes in fish feed affected the metabolism of mice fed diets containing fillets from such farmed salmon. We demonstrate that replacement of fish oil with rapeseed oil or soybean oil in fish feed had distinct spillover effects in mice fed western diets containing the salmon. A reduced ratio of n-3/n-6 polyunsaturated fatty acids in the fish feed, reflected in the salmon, and hence also in the mice diets, led to a selectively increased abundance of arachidonic acid in the phospholipid pool in the livers of the mice. This was accompanied by increased levels of hepatic ceramides and arachidonic acid-derived pro-inflammatory mediators and a reduced abundance of oxylipins derived from eicosapentaenoic acid and docosahexaenoic acid. These changes were associated with increased whole body insulin resistance and hepatic steatosis. Our data suggest that an increased ratio between n-6 and n-3-derived oxylipins may underlie the observed marked metabolic differences between mice fed the different types of farmed salmon. These findings underpin the need for carefully considering the type of oil used for feed production in relation to salmon farming.

Oceans and Human Health (OHH): a European perspective from the Marine Board of the European Science Foundation (Marine Board-ESF).

The oceans and coastal seas provide mankind with many benefits including food for around a third of the global population, the air that we breathe and our climate system which enables habitation of much of the planet. However, the converse is that generation of natural events (such as hurricanes, severe storms and tsunamis) can have devastating impacts on coastal populations, while pollution of the seas by pathogens and toxic waste can cause illness and death in humans and animals. Harmful effects from biogenic toxins produced by algal blooms (HABs) and from the pathogens associated with microbial pollution are also a health hazard in seafood and from direct contact with water. The overall global burden of human disease caused by sewage pollution of coastal waters has been estimated at 4 million lost person-years annually. Finally, the impacts of all of these issues will be exacerbated by climate change. A holistic systems approach is needed. It must consider whole ecosystems, and their sustainability, such as integrated coastal zone management, is necessary to address the highly interconnected scientific challenges of increased human population pressure, pollution and over-exploitation of food (and other) resources as drivers of adverse ecological, social and economic impacts. There is also an urgent and critical requirement for effective and integrated public health solutions to be developed through the formulation of politically and environmentally meaningful policies. The research community required to address "Oceans & Human Health" in Europe is currently very fragmented, and recognition by policy makers of some of the problems, outlined in the list of challenges above, is limited. Nevertheless, relevant key policy issues for governments worldwide include the reduction of the burden of disease (including the early detection of emerging pathogens and other threats) and improving the quality of the global environment. Failure to effectively address these issues will impact adversely on efforts to alleviate poverty, sustain the availability of environmental goods and services and improve health and social and economic stability; and thus, will impinge on many policy decisions, both nationally and internationally. Knowledge exchange (KE) will be a key element of any ensuing research. KE will facilitate the integration of biological, medical, epidemiological, social and economic disciplines, as well as the emergence of synergies between seemingly unconnected areas of science and socio-economic issues, and will help to leverage knowledge transfer across the European Union (EU) and beyond. An integrated interdisciplinary systems approach is an effective way to bring together the appropriate groups of scientists, social scientists, economists, industry and other stakeholders with the policy formulators in order to address the complexities of interfacial problems in the area of environment and human health. The Marine Board of the European Science Foundation Working Group on "Oceans and Human Health" has been charged with developing a position paper on this topic with a view to identifying the scientific, social and economic challenges and making recommendations to the EU on policy-relevant research and development activities in this arena. This paper includes the background to health-related issues linked to the coastal environment and highlights the main arguments for an ecosystem-based whole systems approach.

Intake of farmed Atlantic salmon fed soybean oil increases insulin resistance and hepatic lipid accumulation in mice.

BACKGROUND: To ensure sustainable aquaculture, fish derived raw materials are replaced by vegetable ingredients. Fatty acid composition and contaminant status of farmed Atlantic salmon (Salmo salar L.) are affected by the use of plant ingredients and a spillover effect on consumers is thus expected. Here we aimed to compare the effects of intake of Atlantic salmon fed fish oil (FO) with intake of Atlantic salmon fed a high proportion of vegetable oils (VOs) on development of insulin resistance and obesity in mice. METHODOLOGY/PRINCIPAL FINDINGS: Atlantic salmon were fed diets where FO was partly (80%) replaced with three different VOs; rapeseed oil (RO), olive oil (OO) or soy bean oil (SO). Fillets from Atlantic salmon were subsequently used to prepare Western diets (WD) for a mouse feeding trial. Partial replacement of FO with VOs reduced the levels of polychlorinated biphenyls (PCB) and dichloro-diphenyl-tricloroethanes (DDT) with more than 50% in salmon fillets, in WDs containing the fillets, and in white adipose tissue from mice consuming the WDs. Replacement with VOs, SO in particular, lowered the n-3 polyunsaturated fatty acid (PUFA) content and increased n-6 PUFA levels in the salmon fillets, in the prepared WDs, and in red blood cells collected from mice consuming the WDs. Replacing FO with VO did not influence obesity development in the mice, but replacement of FO with RO improved glucose tolerance. Compared with WD-FO fed mice, feeding mice WD-SO containing lower PCB and DDT levels but high levels of linoleic acid (LA), exaggerated insulin resistance and increased accumulation of fat in the liver. CONCLUSION/SIGNIFICANCE: Replacement of FO with VOs in aqua feed for farmed salmon had markedly different spillover effects on metabolism in mice. Our results suggest that the content of LA in VOs may be a matter of concern that warrants further investigation.