Correction: Harris et al. Derivation of the Omega-3 Index from EPA and DHA Analysis of Dried Blood Spots from Dogs and Cats. Vet. Sci. 2023, 10, 13.

In the original publication [...].

Effect of dietary krill oil supplementation on horse red blood cell membrane fatty acid composition and blood parameters.

Supplementation with marine-derived n-3 long-chain polyunsaturated fatty acids (LC PUFAs), eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3) is linked to beneficial health effects in both humans and horses. Krill oil (KO), which is extracted from the Antarctic krill (Euphausia superba), is well documented as a safe and biologically available dietary supplement in humans and several animal species, but there is a lack of documentation regarding its effect as a dietary ingredient for horses. The objective of this study was to test whether KO as a dietary supplement had the ability to raise horse red blood cell (RBC) membrane EPA and DHA, expressed as the n-3 index. Five nonworking Norwegian cold-blooded trotter horse geldings (body weight [BW]: 567 ± 38 kg) were supplemented with KO (10 mL/100 kg BW) for 35 days in a longitudinal study. Blood samples were analysed for RBC membrane fatty acid (FA) profile, haematology and serum biochemistry every 7th day. KO was well accepted by all horses, and no adverse health effects were observed during the 35-day trial period. KO supplementation affected the RBC membrane FA profile by increasing the n-3 index from Day 0 to 35 (Day 0: 0.53% vs. Day 35: 4.05% of total RBC FAs). The observed increase in the sum of EPA and DHA (p < 0.001), total n-3 FAs (p < 0.001) and the reduction of n-6 FAs (p < 0.044) resulted in a lower n-6:n-3 ratio (p < 0.001) by Day 35 of KO supplementation. In conclusion, the RBC n-3 index was increased and the general n-6:n-3 ratio was decreased in horses receiving 35-day dietary KO supplementation.

Comparison of Fish, Krill and Flaxseed as Omega-3 Sources to Increase the Omega-3 Index in Dogs.

(1) Background: it is only the longer chain omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (20:5n-3, EPA), and docosahexaenoic acid (22:6n-3, DHA) and not the shorter chain α-linolenic acid (ALA, 18:3n-3) that have been linked to health benefits. (2) Methods: 45 dogs divided into three groups were first given premium dry food for 38 days (baseline). The O3I was then used as a diagnostic tool to provide a measure of the sum of EPA + DHA in red blood cell membranes given as a percentage of all fatty acids. The dogs were subsequently fed with either krill meal (krill), fishmeal/oil (fish) or flaxseed cake (flax) included in raw food providing daily 416 mg EPA + DHA (971 mg ALA), 513 mg EPA + DHA (1027 mg ALA) and 1465 mg ALA (122 mg EPA + DHA), respectively. (3) Results: the average baseline O3I level of all dogs was low (1.36%), warranting n-3 supplementation. After four weeks, O3I levels were significantly increased in the krill (from 1.36 ± 0.44 to 2.36 ± 0.39%) and fish (from 1.35 ± 0.22 to 1.9 ± 0.35%) groups (p < 0.001). No significant modification of the O3I was detected in the flax animals. (4) Conclusions: only marine n-3 PUFAs resulted in a significantly increased O3I, with dietary krill meal providing the highest increase.

Derivation of the Omega-3 Index from EPA and DHA Analysis of Dried Blood Spots from Dogs and Cats.

The Omega-3 Index (O3I) is the red blood cell (RBC) eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) content expressed as a percentage of total RBC fatty acids. Although a validated biomarker of omega-3 status in humans, little is known about the O3I status of dogs and cats; species in which omega-3 fatty acids have known health benefits. The purpose of this study was to develop equations to predict the O3I in these species from a dried blood spot (DBS) analysis. Random blood samples from 33 dogs and 10 cats were obtained from a community veterinary clinic. DBS and RBC samples were analyzed for fatty acid composition. For both species, the R2 between the DBS EPA + DHA value and the O3I was >0.96 (p < 0.001). The O3I was roughly 75% lower in dogs and cats than in humans. We conclude that the O3I can be estimated from a DBS sample, and the convenience of DBS collection should facilitate omega-3 research in these companion animals.

Krill-Oil-Dependent Increases in HS-Omega-3 Index, Plasma Choline and Antioxidant Capacity in Well-Conditioned Power Training Athletes.

There is evidence that both omega-3 polyunsaturated fatty acids (n-3 PUFAs) and choline can influence sports performance, but information establishing their combined effects when given in the form of krill oil during power training protocols is missing. The purpose of this study was therefore to characterize n-3 PUFA and choline profiles after a one-hour period of high-intensity physical workout after 12 weeks of supplementation. Thirty-five healthy power training athletes received either 2.5 g/day of Neptune krill oilTM (550 mg EPA/DHA and 150 mg choline) or olive oil (placebo) in a randomized double-blind design. After 12 weeks, only the krill oil group showed a significant HS-Omega-3 Index increase from 4.82 to 6.77% and a reduction in the ARA/EPA ratio (from 50.72 to 13.61%) (p < 0.001). The krill oil group showed significantly higher recovery of choline concentrations relative to the placebo group from the end of the first to the beginning of the second exercise test (p = 0.04) and an 8% decrease in total antioxidant capacity post-exercise versus 21% in the placebo group (p = 0.35). In conclusion, krill oil can be used as a nutritional strategy for increasing the HS-Omega-3 Index, recover choline concentrations and address oxidative stress after intense power trainings.

Enhanced omega-3 index after long- versus short-chain omega-3 fatty acid supplementation in dogs.

BACKGROUND: The Omega-3 Index is a test that measures the amount of the long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in red blood cell membranes, which is expressed as a percentage of all fatty acids. However, alpha-linolenic acid (ALA) from flaxseed oil, which is a short-chain n-3 PUFA, is often promoted in pet feed as a n-3 source, implicitly assuming it is an effective precursor of EPA and DHA. OBJECTIVE: This study was aimed to compare the effect of supplementation with a plant-based short-chain n-3 PUFA source (flaxseed oil, FSO) with a marine long-chain n-3 PUFA source (astaxanthin krill oil, AKO) to increase the Omega-3 Index in dogs. METHODS: Ten adult Alaskan Huskies of both genders were supplemented daily with 1,155 mg of EPA/DHA from AKO, whereas another 10 dogs received 1,068 mg ALA from flaxseed oil for 6 weeks. Fatty acid and Omega-3 Index measurements of the two groups were taken after 0, 3 and 6 weeks for comparison. RESULTS: The EPA and DHA concentrations increased significantly only in the dogs fed with AKO resulting in a significant increase in mean Omega-3 Index, from 1.68% at baseline to 2.7% after 6 weeks of supplementation (p < .0001). On the contrary, both EPA and DHA concentrations decreased significantly in the dogs fed with FSO, which led to a significant decrease in mean Omega-3 Index from 1.6% at baseline to 0.96% at study end (p < .0001). CONCLUSIONS: The results showed that supplementation of AKO from Antarctic krill led to a significant increase in the Omega-3 Index in comparison to FSO in dogs. This suggests that preformed marine EPA and DHA sources are needed in dog feeds, as the dietary requirements proposed by feed industry organizations are not met with conversion from short-chain n-3 fatty acids.

Effects of Krill Oil and Race Distance on Serum Choline and Choline Metabolites in Triathletes: A Field Study.

Choline is an essential nutrient that has been implicated in athletic performance due to its role in maintaining normal muscle function. The concentration of free choline in serum may decrease during long-distance high-intensity exercise, yet few nutritional strategies to counteract this potentially performance-depleting loss in choline have been investigated outside the laboratory. This exploratory field study was performed to investigate if pre-race supplementation with phosphatidylcholine from krill oil can counteract the expected drop in choline and some of its metabolites during triathlon competitions. Forty-seven triathletes, 12 females and 35 males ranging in age from 25 to 61 years, were recruited from participants in the Ironman-distance Norseman Xtreme triathlon and the Sprint/Olympic-distance Oslo Triathlon. Twenty-four athletes were randomly allocated to the krill oil group, receiving 4 g of SuperbaBoost™ krill oil daily for 5 weeks prior to the race, and 23 athletes were randomly allocated to the placebo group, receiving 4 g of mixed vegetable oil daily. Blood samples were obtained before the race, immediately after completion of the race, and the day after the race for analysis of choline and its metabolites. The results showed that serum choline concentrations significantly decreased from pre-race to race finish in all races, with a more pronounced decrease observed in the Ironman-distance Norseman Xtreme triathlon (34% decrease) relative to the Sprint/Olympic-distance Oslo Triathlon (15% decrease). A reduction in betaine was also observed, while dimethylglycine (DMG) concentrations remained stable across all time points. Significantly higher concentrations of choline (9.4% on average) and DMG (21.4% on average) were observed in the krill oil compared to the placebo group, and the krill oil group showed a significantly greater increase in serum choline following race completion. In conclusion, krill oil may help to prevent that circulating choline concentrations become limiting during endurance competitions.

Higher omega-3 index after dietary inclusion of omega-3 phospholipids versus omega-3 triglycerides in Alaskan Huskies.

BACKGROUND AND AIM: Numerous studies have found benefits of omega-3 polyunsaturated fatty acids (PUFAs), namely, for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in dogs. The objective of the present study was to assess the efficacy of dietary inclusion of equal amounts of omega-3 FAs in phospholipid (PL) from krill meal to triglyceride structure from fish oil to increase the omega-3 FA profile in red blood cells (RBCs) in dogs. MATERIALS AND METHODS: Ten adult Alaskan Huskies of both genders were supplemented with daily 1.7 g EPA and DHA from krill meal for 6 weeks, while another ten dogs received 1.7 g EPA and DHA from fish oil. FA and omega-3 index measurements of the two groups were taken after 0, 3, and 6 weeks for comparison. RESULTS: It was mainly the EPA levels that increased in the krill meal group (from 1.84% to 4.42%) compared to the fish oil group (from 1.90% to 2.46%) (p<0.001), which drove the group differences in the omega-3 index. This resulted in the krill meal group having a mean omega-3 index increase from 3.9 at baseline to 6.3%, which was significantly greater than the increase from 3.9% to 4.7% observed in the fish oil group (p<0.001). Concomitantly, omega-6 PUFAs, such as arachidonic acid and linoleic acid, were reduced in RBC membranes and the omega-6 to omega-3 ratio was significantly more reduced in the krill meal compared to the fish oil group. CONCLUSION: The results showed that krill meal supplementation was associated with a reduction of omega-6 PUFAs, which compensated for the increased omega-3 index, suggesting that PLs are efficient delivery molecules of omega-3 PUFAs.

The PPAR pan-agonist tetradecylthioacetic acid promotes redistribution of plasma cholesterol towards large HDL.

Tetradecylthioacetic acid (TTA) is a synthetic fatty acid with a sulfur substitution in the ß-position. This modification renders TTA unable to undergo complete ß-oxidation and increases its biological activity, including activation of peroxisome proliferator activated receptors (PPARs) with preference for PPARα. This study investigated the effects of TTA on lipid and lipoprotein metabolism in the intestine and liver of mice fed a high fat diet (HFD). Mice receiving HFD supplemented with 0.75% (w/w) TTA had significantly lower body weights compared to mice fed the diet without TTA. Plasma triacylglycerol (TAG) was reduced 3-fold with TTA treatment, concurrent with increase in liver TAG. Total cholesterol was unchanged in plasma and liver. However, TTA promoted a shift in the plasma lipoprotein fractions with an increase in larger HDL particles. Histological analysis of the small intestine revealed a reduced size of lipid droplets in enterocytes of TTA treated mice, accompanied by increased mRNA expression of fatty acid transporter genes. Expression of the cholesterol efflux pump Abca1 was induced in the small intestine, but not in the liver. Scd1 displayed markedly increased mRNA and protein expression in the intestine of the TTA group. It is concluded that TTA treatment of HFD fed mice leads to increased expression of genes involved in uptake and transport of fatty acids and HDL cholesterol in the small intestine with concomitant changes in the plasma profile of smaller lipoproteins.

Phosphatidylcholine from krill increases plasma choline and its metabolites in dogs.

BACKGROUND AND AIM: Choline and its metabolites have multiple physiological roles in the body, which are important for muscle function, memory, methylation reactions, and hepatic lipid transport. This study aimed to investigate, if inclusion of phosphatidylcholine (PC) from Antarctic krill (Euphausia superba) can increase the concentration of choline and its metabolites in plasma of sled dogs in comparison to a control group. MATERIALS AND METHODS: Ten adult Alaskan Huskies of both genders were supplemented with PC from 8% dietary krill meal inclusion for 6 weeks, while another ten dogs received no krill meal supplementation. Blood measurements of the two groups were taken at baseline and end of the study and compared for choline and its metabolite concentrations. RESULTS: The choline concentration of the krill meal-supplemented dogs was significantly higher after 6 weeks of krill meal feeding compared to the control group (mean increase = 4.53 µmol/L in the supplemented versus 1.21 µmol/L in the control group, p=0.014). Furthermore, krill meal-supplemented dogs showed significantly more pronounced increases in betaine (p<0.001), dimethylglycine (p<0.01), trimethylamine-N-oxide (p<0.001), and trimethyllysine (p<0.001) compared to the control group. Significant correlations between changes in choline and changes in its metabolites were observed. CONCLUSION: The results showed that krill meal supplementation was associated with significantly higher plasma choline concentrations, which correlated with changed concentrations of choline metabolites.

Effects of dietary supplementation with krill meal on serum pro-inflammatory markers after the Iditarod sled dog race.

A seafood-based supplement from krill, rich in omega-3 phospholipids and proteins was tested on a group of dogs competing in the 2016 Iditarod dog sled race to investigate the effects of krill meal on exercise-induced inflammation and muscle damage in comparison to a control group. A single team of 16 dogs received 8% krill meal for 5 weeks prior to the start of race, while another team of 16 dogs received no supplementation. Ten dogs of the treatment and 11 dogs of the control group finished the race and their blood was analyzed for omega-3 index, inflammation (CRP) and muscle damage (CK). The omega-3 index of the krill meal-fed dogs was significantly higher at the beginning of the race (mean 6.2% in the supplemented vs 5.2% in the control group, p < .001). CRP concentrations increased from 7.05 ±â€¯2.27 to 37.04 ±â€¯9.16 µg/ml in the control and from 4.26 ±â€¯0.69 to 16.56 ±â€¯3.03 µg/ml in the treatment group, with a significant difference between the groups (p < .001). CK activity was increased from 90.75 ±â€¯8.15 IU/l to 715.90 ±â€¯218.9 IU/l in the control group and from 99.55 ±â€¯12.15 to 515.69 ±â€¯98.98 in the supplemented group, but there were no differences between groups (p = .266). The results showed that krill meal supplementation led to significantly higher omega-3 index, which correlated with lower inflammation and a tendency for reduced muscle damage after this long-distance sled dog competition. However, these results need to be confirmed by more controlled studies, since it was a field study and effects of race speed or other performance-related factors such as fitness and musher skill on the results cannot be excluded.

Fish oil and krill oil differentially modify the liver and brain lipidome when fed to mice.

BACKGROUND: Marine food is an important source of omega-3 fatty acids with beneficial health effects. Oils from marine organisms have different fatty acid composition and differ in their molecular composition. Fish oil (FO) has a high content of eicosapentaenoic and docosahexaenoic acids mainly esterified to triacylglycerols, while in krill oil (KO) these fatty acids are mainly esterified to phospholipids. The aim was to study the effects of these oils on the lipid content and fatty acid distribution in the various lipid classes in liver and brain of mice. METHODS: Mice were fed either a high-fat diet (HF), a HF diet supplemented with FO or with KO (n = 6). After six weeks of feeding, liver and brain lipid extracts were analysed using a shotgun and TAG lipidomics approach. Student t-test was performed after log-transformation to compare differences between study groups. RESULTS: Six weeks of feeding resulted in significant changes in the relative abundance of many lipid classes compared to control mice. In both FO and KO fed mice, the triacylglycerol content in the liver was more than doubled. The fatty acid distribution was affected by the oils in both liver and brain with a decrease in the abundance of 18:2 and 20:4, and an increase in 20:5 and 22:6 in both study groups. 18:2 decreased in all lipid classes in the FO group but with only minor changes in the KO group. Differences between the feeding groups were particularly evident in some of the minor lipid classes that are associated with inflammation and insulin resistance. Ceramides and diacylglycerols were decreased and cholesteryl esters increased in the liver of the KO group, while plasmalogens were decreased in the FO group. In the brain, diacylglycerols were decreased, more by KO than FO, while ceramides and lactosylceramides were increased, more by FO than KO. CONCLUSION: The changes in the hepatic sphingolipids and 20:4 fatty acid levels were greater in the KO compared to the FO fed mice, and are consistent with a hypothesis that krill oil will have a stronger anti-inflammatory action and enhances insulin sensitivity more potently than fish oil.

Krill products: an overview of animal studies.

Many animal studies have been performed with krill oil (KO) and this review aims to summarize their findings and give insight into the mechanism of action of KO. Animal models that have been used in studies with KO include obesity, depression, myocardial infarction, chronic low-grade and ulcerative inflammation and are described in detail. Moreover, studies with KO in the form of krill powder (KP) and krill protein concentrate (KPC) as a mix of lipids and proteins are mentioned and compared to the effects of KO. In addition, differences in tissue uptake of the long-chain omega-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), when delivered in either phospholipid or triglyceride form, are addressed and the differential impact the delivery form has on gene expression profiles is explained. In our outlook, we try to highlight the potential of KO and KP supplementation in clinical settings and discuss health segments that have a high potential of showing krill product specific health benefits and warrant further clinical investigations.

Effect of fish and krill oil supplementation on glucose tolerance in rabbits with experimentally induced obesity.

PURPOSE: This study was conducted to investigate the effect of fish oil (FO) and krill oil (KO) supplementation on glucose tolerance in obese New Zealand white rabbits. METHODS: The experiments were carried out with 24 male rabbits randomly divided into four groups: KO-castrated, treated with KO; FO-castrated, treated with FO; C-castrated, non-treated; NC-non-castrated, non-treated. At the end of treatment period (2 months), an intravenous glucose tolerance test (IVGTT) was performed in all rabbits. RESULTS: Fasting blood glucose concentrations in FO and KO animals were significantly lower than in group C. The blood glucose concentrations in FO- and KO-treated animals returned to initial values after 30 and 60 min of IVGTT, respectively. In liver, carnitine palmitoyltransferase 2 (Cpt2) and 3-hydroxy-3-methyl-glutaryl-CoA synthase 2 (Hmgcs2) genes were significantly increased in FO-fed rabbits compared with the C group. Acetyl-CoA carboxylase alpha (Acaca) expression was significantly reduced in both KO- and FO-fed rabbits. In skeletal muscle, Hmgcs2 and Cd36 were significantly higher in KO-fed rabbits compared with the C group. Acaca expression was significantly lower in KO- and FO-fed rabbits compared with the C group. CONCLUSION: The present results indicate that FO and KO supplementation decreases fasting blood glucose and improves glucose tolerance in obese New Zealand white rabbits. This could be ascribed to the ameliorated insulin sensitivity and insulin secretion and modified gene expressions of some key enzymes involved in ß-oxidation and lipogenesis in liver and skeletal muscle.

Safety assessment of Superba™ krill powder: Subchronic toxicity study in rats.

The safety of krill powder was assessed in a subchronic 13-week toxicity study where rats were fed krill powder or control diets. The krill powder inclusion in the test diet was 9.67% (w/w). There were no differences noted in body weight or food consumption in either gender. Differences in clinical chemistry values were noted in the krill powder-treated animals, but these findings were of no toxicological significance. A significant decrease in absolute heart weight, but not relative heart weight, was observed in both sexes given krill powder, although no corresponding histological changes were observed. Hepatocyte vacuolation was noted histologically in males fed krill powder. This finding was not associated with other indications of hepatic dysfunction. The no observed adverse effect level (NOAEL) for the conditions of this study was considered to be 9.67% krill powder.

Fish oil and krill oil supplementations differentially regulate lipid catabolic and synthetic pathways in mice.

BACKGROUND: Marine derived oils are rich in long-chain polyunsaturated omega-3 fatty acids, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have long been associated with health promoting effects such as reduced plasma lipid levels and anti-inflammatory effects. Krill oil (KO) is a novel marine oil on the market and is also rich in EPA and DHA, but the fatty acids are incorporated mainly into phospholipids (PLs) rather than triacylglycerols (TAG). This study compares the effects of fish oil (FO) and KO on gene regulation that influences plasma and liver lipids in a high fat diet mouse model. METHODS: Male C57BL/6J mice were fed either a high-fat diet (HF) containing 24% (wt/wt) fat (21.3% lard and 2.3% soy oil), or the HF diet supplemented with FO (15.7% lard, 2.3% soy oil and 5.8% FO) or KO (15.6% lard, 2.3% soy oil and 5.7% KO) for 6 weeks. Total levels of cholesterol, TAG, PLs, and fatty acid composition were measured in plasma and liver. Gene regulation was investigated using quantitative PCR in liver and intestinal epithelium. RESULTS: Plasma cholesterol (esterified and unesterified), TAG and PLs were significantly decreased with FO. Analysis of the plasma lipoprotein particles indicated that the lipid lowering effect by FO is at least in part due to decreased very low density lipoprotein (VLDL) content in plasma with subsequent liver lipid accumulation. KO lowered plasma non-esterified fatty acids (NEFA) with a minor effect on fatty acid accumulation in the liver. In spite of a lower omega-3 fatty acid content in the KO supplemented diet, plasma and liver PLs omega-3 levels were similar in the two groups, indicating a higher bioavailability of omega-3 fatty acids from KO. KO more efficiently decreased arachidonic acid and its elongation/desaturation products in plasma and liver. FO mainly increased the expression of several genes involved in fatty acid metabolism, while KO specifically decreased the expression of genes involved in the early steps of isoprenoid/cholesterol and lipid synthesis. CONCLUSIONS: The data show that both FO and KO promote lowering of plasma lipids and regulate lipid homeostasis, but with different efficiency and partially via different mechanisms.

Krill oil supplementation lowers serum triglycerides without increasing low-density lipoprotein cholesterol in adults with borderline high or high triglyceride levels.

The aim of the study was to explore the effects of 12 weeks daily krill oil supplementation on fasting serum triglyceride (TG) and lipoprotein particle levels in subjects whose habitual fish intake is low and who have borderline high or high fasting serum TG levels (150-499 mg/dL). We hypothesized that Krill oil lowers serum TG levels in subjects with borderline high or high fasting TG levels. To test our hypothesis 300 male and female subjects were included in a double-blind, randomized, multi-center, placebo-controlled study with five treatment groups: placebo (olive oil) or 0.5, 1, 2, or 4 g/day of krill oil. Serum lipids were measured after an overnight fast at baseline, 6 and 12 weeks. Due to a high intra-individual variability in TG levels, data from all subjects in the four krill oil groups were pooled to increase statistical power, and a general time- and dose-independent one-way analysis of variance was performed to assess efficacy. Relative to subjects in the placebo group, those administered krill oil had a statistically significant calculated reduction in serum TG levels of 10.2%. Moreover, LDL-C levels were not increased in the krill oil groups relative to the placebo group. The outcome of the pooled analysis suggests that krill oil is effective in reducing a cardiovascular risk factor. However, owing to the individual fluctuations of TG concentrations measured, a study with more individual measurements per treatment group is needed to increase the confidence of these findings.

Genotoxicity test and subchronic toxicity study with Superba™ krill oil in rats.

The safety of krill oil was assessed in a subchronic toxicity study and in a genotoxicity test. In a 13-week study, rats were fed krill oil or control diets. There were no differences noted in body weight, food consumption or in the functional observation battery parameters in either gender. Differences in both haematology and clinical chemistry values were noted in the krill oil-treated groups. However these findings were of no toxicological significance. Significant decreases in absolute and covariant heart weight in some krill oil-treated animals were noted although no corresponding histological changes were observed. In addition, periportal microvesicular hepatocyte vacuolation was noted histologically in males fed 5% krill oil. This finding was not associated with other indications of hepatic dysfunction. Given that the effects of the 13-week toxicity study were non-toxic in nature, the no observed adverse effect level (NOAEL) for the conditions of this study was considered to be 5% krill oil. The genotoxicity experiments documented no mutagenicity of krill oil in bacteria.

Enhanced cognitive function and antidepressant-like effects after krill oil supplementation in rats.

BACKGROUND: The purpose of the study was to evaluate the effects of krill oil (KO) on cognition and depression-like behaviour in rats. METHODS: Cognition was assessed using the Aversive Light Stimulus Avoidance Test (ALSAT). The Unavoidable Aversive Light Stimulus (UALST) and the Forced Swimming Test (FST) were used to evaluate the antidepressant-like effects of KO. Imipramine (IMIP) was used as the antidepressant reference substance. RESULTS: After 7 weeks of KO intake, both males and females treated with KO were significantly better in discriminating between the active and the inactive levers in the ALSAT from day 1 of training (p<0.01). Both KO and IMIP prevented resignation/depression on the third day in the UALST. Similarly, a shorter immobility time was observed for the KO and IMIP groups compared to the control in the FST (p<0.001). These data support a robust antidepressant-like potential and beneficial cognitive effect of KO. Changes in expression of synaptic plasticity-related genes in the prefrontal cortex and hippocampus were also investigated. mRNA for brain-derived neurotrophic factor (Bdnf) was specifically upregulated in the hippocampus of female rats receiving 7 weeks of KO supplementation (p=0.04) and a similar trend was observed in males (p=0.08). Males also exhibited an increase in prefrontal cortex expression of Arc mRNA, a key protein in long-term synaptic plasticity (p=0.05). IMIP induced clear effects on several plasticity related genes including Bdnf and Arc. CONCLUSIONS: These results indicate that active components (eicosapentaenoic acid, docosahexaenoic acid and astaxanthin) in KO facilitate learning processes and provide antidepressant-like effects. Our findings also suggest that KO might work through different physiological mechanisms than IMIP.

Induction of mitochondrial biogenesis and respiration is associated with mTOR regulation in hepatocytes of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA).

The hypolipidemic effect of peroxisome proliferator-activated receptor (PPAR) activators has been explained by increasing mitochondrial fatty acid oxidation, as observed in livers of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA). PPAR-activation does, however, not fully explain the metabolic adaptations observed in hepatocytes after treatment with TTA. We therefore characterized the mitochondrial effects, and linked this to signalling by the metabolic sensor, the mammalian target of rapamycin (mTOR). In hepatocytes isolated from TTA-treated rats, the changes in cellular content and morphology were consistent with hypertrophy. This was associated with induction of multiple mitochondrial biomarkers, including mitochondrial DNA, citrate synthase and mRNAs of mitochondrial proteins. Transcription analysis further confirmed activation of PPARα-associated genes, in addition to genes related to mitochondrial biogenesis and function. Analysis of mitochondrial respiration revealed that the capacity of both electron transport and oxidative phosphorylation were increased. These effects coincided with activation of the stress related factor, ERK1/2, and mTOR. The protein level and phosphorylation of the downstream mTOR actors eIF4G and 4E-BP1 were induced. In summary, TTA increases mitochondrial respiration by inducing hypertrophy and mitochondrial biogenesis in rat hepatocytes, via adaptive regulation of PPARs as well as mTOR.