Fish oil supplementation during pregnancy decreases liver endocannabinoid system and lipogenic markers in newborn rats exposed to maternal high-fat diet.

PURPOSE: Maternal high-fat diet (HF) programs obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), hypertriglyceridemia, and hyperglycemia associated with increased endocannabinoid system (ECS) in the liver of adult male rat offspring. We hypothesized that maternal HF would induce sex specific ECS changes in the liver of newborn rats, prior to obesity onset, and maternal fish oil (FO) supplementation would reprogram the ECS and lipid metabolism markers preventing liver triglycerides (TG) accumulation. METHODS: Female rats received a control (CT) (10.9% fat) or HF (28.7% fat) diet 8 weeks prior to mating and during pregnancy. A subgroup of HF dams received 3% FO supplementation in the HF diet (35.4% fat) during pregnancy (HFFO). Serum hormones and liver TG, ECS, lipid metabolism, oxidative stress and autophagy markers were assessed in male and female newborn offspring. RESULTS: Maternal HF diet increased liver cannabinoid receptor 1 (CB1) in males and decreased CB2 in females, with no effect on liver TG. Maternal FO supplementation reduced liver CB1 regardless of the offspring sex, but reduced TG liver content only in females. FO reduced the liver content of the endocannabinoid anandamide in males, and the content of 2-arachidonoylglycerol in both sexes. Maternal HF increased lipogenic and decreased lipid oxidation markers, and FO induced the opposite regulation in the liver of offspring. CONCLUSION: Prenatal HF and FO differentially modulate liver ECS in the offspring before obesity and MASLD development. These results suggest that maternal nutrition at critical stages of development can modulate the offspring's ECS, predisposing or preventing the onset of metabolic diseases.

Effect of Dietary Supplementation with Omega-3 Fatty Acid on the Generation of Regulatory T Lymphocytes and on Antioxidant Parameters and Markers of Oxidative Stress in the Liver Tissue of IL-10 Knockout Mice.

INTRODUCTION: chronic low-grade inflammation, or inflammaging, emerges as a crucial element in the aging process and is associated with cardiovascular and neurological diseases, sarcopenia, and malnutrition. Evidence suggests that omega-3 fatty acids present a potential therapeutic agent in the prevention and treatment of inflammatory diseases, mitigating oxidative stress, and improving muscle mass, attributes that are particularly relevant in the context of aging. The objective of the present study was to evaluate the effectiveness of supplementation with omega-3 fish oil in improving the immune response and oxidative stress in knockout mice for interleukin IL-10 (IL-10-/-). MATERIAL AND METHODS: female C57BL/6 wild-type (WT) and interleukin IL-10 knockout (IL-10-/-) mice were fed during 90 days with a standard diet (control groups), or they were fed/supplemented with 10% of the omega-3 polyunsaturated fatty acid diet (omega-3 groups). Muscle, liver, intestinal, and mesenteric lymph node tissue were collected for analysis. RESULTS: the IL-10-/-+O3 group showed greater weight gain compared to the WT+O3 (p = 0.001) group. The IL-10-/-+O3 group exhibited a higher frequency of regulatory T cells than the IL-10-/- group (p = 0.001). It was found that animals in the IL-10-/-+O3 group had lower levels of steatosis when compared to the IL-10-/- group (p = 0.017). There was even greater vitamin E activity in the WT group compared to the IL-10-/-+O3 group (p = 0.001) and WT+O3 compared to IL-10-/-+O3 (p = 0.002), and when analyzing the marker of oxidative stress, MDA, an increase in lipid peroxidation was found in the IL-10-/-+O3 group when compared to the IL-10-/- group (p = 0.03). Muscle tissue histology showed decreased muscle fibers in the IL-10-/-+O3, IL-10-/-, and WT+O3 groups. CONCLUSION: the findings show a decrease in inflammation, an increase in oxidative stress markers, and a decrease in antioxidant markers in the IL-10-/-+O3 group, suggesting that supplementation with omega-3 fish oil might be a potential intervention for inflammaging that characterizes the aging process and age-related diseases.

DHA-rich fish oil plays a protective role against experimental cerebral malaria by controlling inflammatory and mechanical events from infection.

Every year, thousands of children, particularly those under 5 years old, die because of cerebral malaria (CM). Following conventional treatment, approximately 25% of surviving individuals have lifelong severe neurocognitive sequelae. Therefore, improved conventional therapies or effective alternative therapies that prevent the severe infection are crucial. Omega-3 (Ω-3) polyunsaturated fatty acids (PUFAs) are known to have antioxidative and anti-inflammatory effects and protect against diverse neurological disorders, including Alzheimer's and Parkinson's diseases. However, little is known regarding the effects of Ω-3 PUFAs against parasitic infections. In this study, C57BL/6 mice received supplemental treatment of a fish oil rich in the Ω-3 PUFA, docosahexaenoic acid (DHA), which was started 15 days prior to infection with Plasmodium berghei ANKA and was maintained until the end of the study. Animals treated with the highest doses of DHA, 3.0 and 6.0 g/kg body weight, had 60 and 80% chance of survival, respectively, while all nontreated mice died by the 7th day postinfection due to CM. Furthermore, the parasite load during the critical period for CM development (5th to 11th day postinfection) was controlled in treated mice. However, after this period all animals developed high levels of parasitemia until the 20th day of infection. DHA treatment also effectively reduced blood-brain barrier (BBB) damage and brain edema and completely prevented brain hemorrhage and vascular occlusion. A strong anti-inflammatory profile was observed in the brains of DHA-treated mice, as well as, an increased number of neutrophil and reduced number of CD8+ T leukocytes in the spleen. Thus, this is the first study to demonstrate that the prophylactic use of DHA-rich fish oil exerts protective effects against experimental CM, reducing the mechanical and immunological events caused by the P. berghei ANKA infection.

Fish Oil Supplementation Improves the Repeated-Bout Effect and Redox Balance in 20-30-Year-Old Men Submitted to Strength Training.

Herein, we investigated the effect of fish oil supplementation combined with a strength-training protocol, for 6 weeks, on muscle damage induced by a single bout of strength exercise in untrained young men. Sixteen men were divided into two groups, supplemented or not with fish oil, and they were evaluated at the pre-training period and post-training period. We investigated changes before and 0, 24, and 48 h after a single hypertrophic exercise session. Creatine kinase (CK) and lactate dehydrogenase (LDH) activities, plasma interleukin-6 (IL-6) and C-reactive protein (CRP) levels, and the redox imbalance were increased in response to the single-bout session of hypertrophic exercises at baseline (pre-training period) and decreased during the post-training period in the control group due to the repeated-bout effect (RBE). The fish oil supplementation exacerbated this reduction and improved the redox state. In summary, our findings demonstrate that, in untrained young men submitted to a strength-training protocol, fish oil supplementation is ideal for alleviating the muscle injury, inflammation, and redox imbalance induced by a single session of intense strength exercises, highlighting this supplementation as a beneficial strategy for young men that intend to engage in strength-training programs.

Effect of a parenteral fish-oil-containing lipid emulsion on liver lipid perioxidation and antioxidative defenses in Lewis rats.

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), naturally abundant in fish oil (FO), are known for their anti-inflammatory and potential antioxidant properties. The aim in this article is to evaluate the effect of the infusion of a parenteral FO-containing lipid emulsion on markers of liver lipid peroxidation and oxidative stress in rats undergoing central venous catheterization (CVC). METHODS: After 5-day acclimatization, adult Lewis rats (n = 42) receiving a 20-g/day AIN-93M oral diet were randomly subdivided into four groups: (1) basal control (BC) (n = 6), without CVC or LE infusion; (2) SHAM (n = 12), with CVC but without LE infusion; (3) soybean oil (SO)/medium-chain triglyceride (MCT) (n = 12), with CVC and receiving LE without FO (4.3 g/kg fat); and (4) SO/MCT/FO (n = 12), with CVC and receiving LE containing 10% FO (4.3 g/kg fat). Animals from the BC group were euthanized immediately after acclimatization. The remaining groups of animals were euthanized after 48 or 72 h of surgical follow-up to assess profiles of liver and plasma fatty acids by gas chromatography, liver gene transcription factor Nrf2, F2-isoprostane lipid peroxidation biomarker, and the antioxidant enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) by enzyme-linked immunosorbent assay. R program (version 3.2.2) was utilized for data analysis. RESULTS: Compared with the other groups, liver EPA and DHA levels were higher in the SO/MCT/FO group, which also showed the highest liver Nrf2, GPx, SOD, and CAT levels and lower liver F2-isoprostane (P < 0.05). CONCLUSION: Experimental delivery of FO via EPA and DHA sources in a parenteral LE was associated with a liver antioxidant effect.

Effect of Gestational Fish Oil Supplementation on Liver Metabolism and Mitochondria of Male and Female Rat Offspring Programmed by Maternal High-Fat Diet.

SCOPE: Perinatal maternal moderately high-fat diet (mHFD) is associated with obesity and fatty liver disease in offspring, and maternal fish oil (FO: n-3 PUFA source) supplementation may attenuate these disorders. This study evaluates the effects of FO given to pregnant rats fed a mHFD on the offspring's liver at weaning. METHODS AND RESULTS: Female Wistar rats receive an isoenergetic, control (CT: 10.9% from fat) or high-fat (HF: 28.7% from fat) diet before mating, and throughout pregnancy and lactation. FO supplementation (HFFO: 2.9% of FO in the HF diet) is given to one subgroup of HF dams during pregnancy. At weaning, male and female mHFD offspring display higher body mass, adiposity, and hepatic cellular damage, steatosis, and inflammation, accompanied by increased damaged mitochondria. FO does not protect pups from systemic metabolic alterations and partially mitigates hepatic histological damage induced by mHFD only in females. However, FO reduces mRNA expression of lipogenic genes, and mitochondrial damage, and modified mitochondrial morphology suggestive of early adaptations via mitochondrial dynamics. CONCLUSIONS: Gestational FO supplementation has limited beneficial effects on the damage caused by perinatal mHFD consumption in offspring's liver at weaning. However, FO imprinting effect on lipid metabolism and mitochondria may have beneficial long-term outcomes.

Effects of fat sources on liver characteristics and intestinal morphometry in an early-life animal model. / Efectos de fuentes de grasa sobre características del hígado y la morfometría intestinal en un modelo animal a temprana edad.

Motivation for the study. There is little evidence on whether the consumption of fat sources containing different proportions of fatty acids has an effect on the characteristics of the liver and small intestine at an early age. Main findings. We found that the intake of fat sources containing unsaturated fatty acids contributes to maintaining the characteristics of both organs; whereas, consumption of sources containing saturated fatty acids favors inflammation in the liver and small intestine. Implications. The consumption of quinoa oil constitutes an alternative to protect these noble organs in an animal model at an early age. We aimed to determine the effect of the consumption of three sources of fatty acids on the relative weight, macroscopic and microscopic characteristics of the liver, and intestinal morphometry in an early-life animal model. Seventy-six randomly distributed chicks received one of the diets (T1: 97.0% basal diet (BD) + 3.0% inert material, T2: 97.0% BD + 3.0% partially hydrogenated vegetable shortening, T3: 97.0% BD + 3.0% quinoa oil, and T4: 97.0% BD + 3.0% fish oil) until the seventh day of life; samples were then extracted in order to be analyzed. We found that the animals that consumed quinoa oil (T3) or fish oil (T4) had favorable results associated to lower liver weight and better absorption of nutrients at intestinal level due to higher values in the hair length and crypt depth ratio, in comparison to partially hydrogenated vegetable shortening (T2). In conclusion, quinoa oil constitutes a healthy option for consumption and an alternative source to fish oil.

Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid supplementation on maternal reproductive parameters.

Conjugated linoleic acid (CLA) is a mixture of positional isomers of linoleic acid found in ruminant products and meat. The diet supplementing with CLA is an emerging area, requiring studies to elucidate its effects on animals and human reproduction, as well as its side effects. Therefore, the aim of this study was to evaluate the effects of CLA gastric administration, during the pregestational and gestational period in biometric and reproductive parameters, as well as in ovarian morphophysiology. Animals were distributed in three groups: (1) control (n = 10); (2) fish oil (n = 10); and (3) CLA (n = 10), that daily received, by gavage, phosphate-buffered saline, fish oil and CLA, respectively, carried out over 50 days (before mating, mating and pregnancy). There was an increment in the nasoanal distance and Lee index of the CLA and fish oil-treated groups during the first weeks (P > 0.05). CLA administration did not affect the ovarian follicle mobilization (P > 0.05), the number of follicles (P > 0.05) and the integrated density of lipid content of oocytes included in antral follicles (P > 0.05). There was no effect of CLA administration on the litter weight (P > 0.05; F2 and F3), however, an increment (P < 0.05) in the number of pups per litter (F2) was observed. Overall, this study demonstrated the absence of side effects of the CLA gastric administration on mice reproductive performance and suggests that this treatment would transgenerationally enhance fertility in this species.

Effects of replacement of dietary fish oil with plant oil on growth performance and fatty acid composition of spinefoot rabbitfish, Siganus rivulatus.

A 95-day feeding study was carried out to evaluate the impact of complete replacement of fish oil by plant oils in the growth performance, feed consumption fatty acid and body composition of juvenile rabbitfish, Siganus rivulatus. There were four treatments i.e., A (fish oil diet), (linseed oil diet), C (soybean meal oil diet) and D (sunflower oil diet). The experimental trial was conducted in twelve 1.5-m3 fiber glass tanks (n=3). Spinefoot rabbitfish juveniles had an average initial weight of 0.948 g ± 0.124 g and they were stocked at 50 fish per tank. Fish fed diet A showed significantly better growth rate, final body weight, and total body weight than fish fed on the other diets. Moreover, the best FCR was observed for diet A followed by diet C and diets B and D had the worst FCR. Fish body composition for crude protein, dry matter, ashes and gross energy at the end of the trial had not differed between the treatments. The highest polyunsaturated fatty acids (PUFA) was found in fish fed diet A followed in decreasing order by diets D, B, and C. Fish oil is a better dietary lipid source for Spinefoot rabbitfish juveniles, Siganus rivulatus, than plant oils. Among plant oils, soybean oil was better than linseed oil and sunflower oil as the main dietary fat source.

Randomised Controlled Trial of Fish Oil Supplementation on Responsiveness to Resistance Exercise Training in Sarcopenic Older Women.

This study aims to investigate the effects of fish oil supplementation on the muscle adaptive response to resistance exercise training, physical performance and serum levels of inflammatory cytokines in sarcopenic older women. A randomised, double-blind, placebo-controlled trial is performed with thirty-four sarcopenic women (2010 European Consensus of Sarcopenia), aged ≥ 65 years. The participants are allocated into the following two groups: Exercise and Fish Oil (EFO) and Exercise and Placebo (EP). Both groups undertook a resistance exercise programme over 14 weeks. All participants are instructed to ingest 4 g/day of food supplements; the EP group received sunflower oil capsules, and the EFO group, fish oil capsules. The cross-sectional area (CSA) of the quadriceps muscle is calculated using magnetic resonance imaging (MRI). The strength of the lower limbs is measured using isokinetic dynamometry. Both groups show improvements in CSA and strength after the intervention. Changes in EFO are significantly greater compared with EP for muscle strength (peak torque, 19.46 Nm and 5.74 Nm, respectively, p < 0.001). CSA increased after the intervention in both groups (EFO; 6.11% and EP; 2.91%), although there is no significant difference between the groups (p = 0.23). There are no significant intra-group, inter-group or time differences in any of the cytokines measured. The use of fish oil supplementation potentiates the neuromuscular response to the anabolic stimulus from training, increasing muscle strength and physical performance in sarcopenic older women.

Effects of Fish Oil Supplementation on Oxidative Stress Biomarkers and Liver Damage in Hypercholesterolemic Rats.

Metabolic syndrome, especially its component related to dyslipidemia, is related to the development of nonalcoholic fatty liver disease (NAFLD), which is a disease with a significant global prevalence. Supplementation with omega-3 polyunsaturated fatty acids emerged as a complementary therapeutic possibility for dyslipidemia, but its benefits are questioned. This paper aims at evaluating the effects of fish oil supplementation in rats with hypercholesterolemia induced by hypercholesterolemic diet (HD). The study design is based on an experimental model in which the animals were randomly divided into 3 groups: G1 (standard commercial feed + saline solution); G2 (hypercholesterolemic diet + saline solution) and G3 (hypercholesterolemic diet + fish oil) over a period of 16 weeks. Metabolic control parameters and oxidative stress biomarkers were evaluated according to standardized methodologies. The G3 group showed significantly lower values of plasma concentrations of TG, and hepatic myeloperoxidase as well as higher erythrocyte superoxide dismutase activity (p < 0.05). Regarding histopathological analysis, there was lipid accumulation in the liver of animals from group G2; meanwhile, hepatocytes reorganization and expressive reduction of lipid vacuoles and hepatic TG content was observed in group G3. This study demonstrated how fish oil supplementation reduced the plasma concentration and hepatic content of triglycerides, as well as liver tissue damage in histopathological analysis.

Preventive treatment with fish oil facilitates the antidepressant-like effect of antidepressant drugs in type-1 diabetes mellitus rats: Implication of serotonergic system.

Treating depression associated with type-1 diabetesmellitus(T1DM) is a major clinical challenge. Fish oil (FO), composed mostly of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has been pointed out as quite promising for the treatment of depression given its neuroprotective property. Although DHA and EPA exert several physiological actions, DHA is known to play a critical role in postnatal brain development. This study aimed to investigate the effect of preventive treatment with FO (with more DHA in the composition) alone or associated with antidepressant drugs on depression-like behaviors and brain monoamines levels of juvenile induced-T1DM rats. Thus, prepubescent rats were submitted to a prolonged treatment with vehicle (VEH) or FO (50% of DHA and 20% EPA) starting 4 weeks before the induction of experimental T1DM (on day 28) by streptozotocin. When combined, the treatment with vehicle, fluoxetine (FLX, a selective serotonin reuptake inhibitor) or imipramine (IMI, a tricyclic antidepressant) started at week 6 (day 42) and lasted for 2 weeks (until day 56). The behavioral tests were conducted on days 55 and 56, followed by hippocampal and prefrontal cortex dissection for neurochemical analyses. Our results showed that induced-T1DM rats pretreated with FO showed a significant increase of EPA and DHA in plasma, indicative of an increase in the systemic availability of these acids. As previously observed, induced-T1DM rats presented increased immobility and decreased swimming and climbing frequencies in the modified forced swimming test, indicative of depressive-like behavior. Only the combined treatment - FO plus antidepressants (FLX or IMI - both in the highest dose) - was able to induce a significant improvement of depressive-like behaviors. Here, it is noteworthy that swimming behavior has been associated with an increase in serotonergic neurotransmission. Interestingly, our data showed that the combined treatment (FO + antidepressants - including the ineffective dose of FLX) was able to increase the swimming of animals more significantly compared to animals not pretreated with FO. In addition, confirming these assumptions, the decreased 5-HT levels in the hippocampus from induced-T1DM rats were increased after treatment with FLX (highest dose) or IMI (both doses), being this increase more pronounced in animal pretreated with FO. Intriguingly, in these animals pretreated with FO, the ineffective dose of FLX in association with FO was able to increase the levels of 5-HT. The decreased hippocampal levels of noradrenaline were increased only after IMI treatment, not being influenced by FO pretreatment. In conclusion, ours results pointed out that the choice of the DHA/EPA ratio may be an important factor to be considered for the FO antidepressant-like effectper se,but the FO treatment in this composition associated with the antidepressant drugs - especially that ones that increase preferentially the availability of 5-HT -, may represent a better alternative of treatment to individuals with T1DM-associated depression.

Short- and Long-Term Effects of Dietary Supplementation with Fish Oil on Inflammatory Pain in Rats.

INTRODUCTION: Dietary supplementation with fish oil is promising as a complementary therapy for inflammatory pain. However, further studies are needed to support its therapeutic potential. For example, the antinociceptive effect of fish oil is widely suggested to be dependent on decreased prostaglandin E2 (PGE2) synthesis, but no previous study has investigated if it affects PGE2-induced nociceptive response. Similarly, beneficial long-term effects on inflammatory response are related to early exposure to fish oil, however, whether these effects include decreased inflammatory pain throughout life is not known. OBJECTIVE: The aim of this study was to investigate the short- and long-term effects of fish oil on inflammatory pain. METHODS: Dietary fish oil supplementation was performed through two protocols: in adult rats, during 20 days, or in dams, during pregnancy and lactation, with tests performed in adult offspring. The hyperalgesic response induced by carrageenan and its final mediators PGE2 and norepinephrine was used to model inflammatory pain. RESULTS: The findings demonstrated for the first time that dietary fish oil (1) decreases the hyperalgesia induced by carrageenan; (2) but not that induced by its final mediator PGE2 and norepinephrine; (3) increase omega-3 polyunsaturated fatty acids in peripheral neural tissue; and (4) attenuates inflammatory pain in individuals exposed to fish oil during pre-natal life and lactation. CONCLUSION: Together, these findings support that fish oil decreases inflammatory pain either when consumed during adult life or during prenatal development. Future studies should confirm the therapeutic potential of fish oil in humans, which is essential for the development of public policies to encourage a fish oil richer diet.

Effects of omega-3 supplementation on muscle damage after resistance exercise in young women: a randomized placebo-controlled trial.

BACKGROUND: Omega-3 is a nutritional strategie that have been used to recover muscles from exercise-induced muscle damage in a preventive perspective. AIM: To verify whether omega-3 (ω-3) supplementation after a session of resistance exercise facilitates muscle recovery in women undergoing a balanced diet. METHODS: This clinical trial was registered under the number NCT02839525. Thirty healthy women (22.2 ± 3.3 years) participated in this double-blinded, placebo-controlled trial. They were randomly distributed into ω-3 (n=15) and placebo (n=15) groups. They ingested ω-3 fish oil (3200 mg/day) or placebo (olive oil) at the dinner after the exercise bout (10 sets of 10 unilateral eccentric contractions in a knee extension chair), as well as at lunch for the three subsequent days. In addition, both groups followed a balanced diet along the four days. Muscle soreness and maximal isometric and isokinetic voluntary contractions were assessed immediately before, and 24, 48, and 72 hours after the resistance exercise. MAIN FINDINGS: There was no significant group-time interaction for any outcome. Participants presented increased levels of muscle soreness and reduced muscle strength capacity along the three days after exercise. There was no difference between placebo and ω-3 groups. CONCLUSION: Supplementation of ω-3 fish oil for three days after resistance exercise provided no additional benefits compared to placebo supplementation on recovery of healthy young women following a balanced diet.

Endoplasmic Reticulum Stress and Autophagy Markers in Soleus Muscle Disuse-Induced Atrophy of Rats Treated with Fish Oil.

Endoplasmic reticulum stress (ERS) and autophagy pathways are implicated in disuse muscle atrophy. The effects of high eicosapentaenoic (EPA) or high docosahexaenoic (DHA) fish oils on soleus muscle ERS and autophagy markers were investigated in a rat hindlimb suspension (HS) atrophy model. Adult Wistar male rats received daily by gavage supplementation (0.3 mL per 100 g b.w.) of mineral oil or high EPA or high DHA fish oils (FOs) for two weeks. Afterward, the rats were subjected to HS and the respective treatments concomitantly for an additional two-week period. After four weeks, we evaluated ERS and autophagy markers in the soleus muscle. Results were analyzed using two-way analysis of variance (ANOVA) and Bonferroni post hoc test. Gastrocnemius muscle ω-6/ω-3 fatty acids (FAs) ratio was decreased by both FOs indicating the tissue incorporation of omega-3 fatty acids. HS altered (p < 0.05) the protein content (decreasing total p38 and BiP and increasing p-JNK2/total JNK2 ratio, and caspase 3) and gene expressions (decreasing BiP and increasing IRE1 and PERK) of ERS and autophagy (decreasing Beclin and increasing LC3 and ATG14) markers in soleus. Both FOs attenuated (p < 0.05) the increase in PERK and ATG14 expressions induced by HS. Thus, both FOs could potentially attenuate ERS and autophagy in skeletal muscles undergoing atrophy.

Effects of fish oil supplementation on spatial memory in rats with pilocarpine-induced epilepsy assessed using the Morris Water Maze test.

OBJECTIVE: Patients with temporal lobe epilepsy (TLE) are at high risk of experiencing cognitive impairment. Such dysfunction is also observed in an animal model of TLE, the rat model of pilocarpine-induced epilepsy. METHODS: We investigated the effects of fish oil supplementation on spatial memory in rats with pilocarpine-induced epilepsy using the Morris Water Maze (MWM) test. RESULTS: Although rats with pilocarpine-induced epilepsy treated with fish oil learned the platform location significantly faster by Day 7 of the acquisition phase, spatial memory performance of these rats was unaffected by fish oil supplementation during probe trials. SIGNIFICANCE: Our study provides insights into the importance of considering nutraceutical strategies for enhancing cognitive abilities in patients with TLE.

Omega-3 Polyunsaturated Fatty Acids Prevent Nonalcoholic Steatohepatitis (NASH) and Stimulate Adipogenesis.

The increasing impact of obesity on global human health intensifies the importance of studies focusing on agents interfering with the metabolism and remodeling not only of the white adipose tissue (WAT) but also of the liver. In the present study, we have addressed the impact of n-3 PUFA in adipose cells' proliferation and adipogenesis, as well as in the hepatic lipid profile and morphology. Mice were induced to obesity by the consumption of a high-fat diet (HFD) for 16 weeks. At the 9th week, the treatment with fish oil (FO) was initiated and maintained until the end of the period. The FO treatment reduced the animals' body mass, plasma lipids, glucose, plasma transaminases, liver mass, triacylglycerol, and cholesterol liver content when compared to animals consuming only HFD. FO also decreased the inguinal (ing) WAT mass, reduced adipocyte volume, increased adipose cellularity (hyperplasia), and increased the proliferation of adipose-derived stromal cells (AdSCs) which corroborates the increment in the proliferation of 3T3-L1 pre-adipocytes or AdSCs treated in vitro with n-3 PUFA. After submitting the in vitro treated (n-3 PUFA) cells, 3T3-L1 and AdSCs, to an adipogenic cocktail, there was an increase in the mRNA expression of adipogenic transcriptional factors and other late adipocyte markers, as well as an increase in lipid accumulation when compared to not treated cells. Finally, the expression of browning-related genes was also higher in the n-3 PUFA treated group. We conclude that n-3 PUFA exerts an attenuating effect on body mass, dyslipidemia, and hepatic steatosis induced by HFD. FO treatment led to decreasing adiposity and adipocyte hypertrophy in ingWAT while increasing hyperplasia. Data suggest that FO treatment might induce recruitment (by increased proliferation and differentiation) of new adipocytes (white and/or beige) to the ingWAT, which is fundamental for the healthy expansion of WAT.

Fish Oil Enriched in EPA, but Not in DHA, Reverses the Metabolic Syndrome and Adipocyte Dysfunction Induced by a High-Fat Diet.

This study aimed to investigate the effects of two commercially available fish oils (FOs) containing different proportions of two omega-3 fatty acids (FA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the metabolic and endocrine dysfunctions of white adipose tissue resulting from obesity. Male C57BL/6J mice, 8 weeks old, received a control or high-fat diet (CO and HF groups, with 9% and 59% energy from fat, respectively) for 8 weeks. The next 8 weeks, the HF group was subdivided into HF, HF+FO/E (HF+5:1 EPA:DHA), and HF+FO/D (HF+5:1 DHA:EPA). Supplementation was performed by gavage, three times a week. All groups that received the HF diet had lower food and caloric intake, but a higher fat intake, body weight (BW) gain, glucose intolerance, and a significant increase in inguinal (ING), retroperitoneal (RP), and epididymal (EPI) adipose tissues when compared to the CO group. Additionally, HF and HF+FO/D groups showed insulin resistance, adipocyte hypertrophy, increased lipolysis and secretion of TNF-α, resistin and IL-10 adipokines by ING and RP adipocytes, and adiponectin only by the HF+FO/D group in ING adipocytes. All of these effects were completely reversed in the HF+FO/E group, which also showed partial reversion in BW gain and glucose intolerance. Both the HF+FO/E and HF+FO/D groups showed a reduction in ING and RP adipose depots when compared to the HF group, but only HF+FO/E in the EPI depot. HF+FO/E, but not HF+FO/D, was able to prevent the changes triggered by obesity in TNF-α, Il-10, and resistin secretion in ING and RP depots. These results strongly suggest that different EPA:DHA ratios have different impacts on the adipose tissue metabolism, FO being rich in EPA, but not in DHA, and effective in reversing the changes induced by obesity.

Fish Oil Emulsion Reduces Liver Injury and Liver Transplantation in Children with Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Study.

OBJECTIVE: To compare the aspartate aminotransferase to platelet ratio index, liver transplantation, and mortality rates between children with intestinal failure-associated liver disease who received fish oil lipid emulsion (FOLE) or soybean oil intravenous lipid emulsion (SOLE). STUDY DESIGN: In this multicenter integrated analysis, FOLE recipients (1 g/kg/d) (n = 189) were compared with historical controls administered SOLE (≤3 g/kg/d) (n = 73). RESULTS: Compared with SOLE, FOLE recipients had a higher direct bilirubin level at baseline (5.8 mg/dL vs 3.0 mg/dL; P < .0001). Among FOLE recipients, 65% experienced cholestasis resolution vs 16% of SOLE recipients (P < .0001). The aspartate aminotransferase to platelet ratio index scores improved in FOLE recipients (1.235 vs 0.810 and 0.758, P < .02) but worsened in SOLE recipients (0.540 vs 2.564 and 2.098; P ≤ .0003) when baseline scores were compared with cholestasis resolution and end of study, respectively. Liver transplantation was reduced in FOLE vs SOLE (4% vs 12%; P = .0245). The probability of liver transplantation in relation to baseline direct or conjugated bilirubin (DB) was lower in FOLE vs SOLE recipients (1% vs 9% at DB of 2 mg/dL; 8% vs 35% at DB of 12.87 mg/dL; P = .0022 for both). Death rates were similar (FOLE vs SOLE: 10% vs 14% at DB of 2 mg/dL; 17% vs 23% at a DB of 12.87 mg/dL; P = .36 for both). CONCLUSIONS: FOLE recipients experienced a higher rate of cholestasis resolution, lower aspartate aminotransferase to platelet ratio index, and fewer liver transplants compared with SOLE. This study demonstrates that FOLE may be the preferred parenteral lipid emulsion in children with intestinal failure-associated liver disease when DB reaches 2 mg/dL. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00910104 and NCT00738101.

Fish oil attenuated dystrophic muscle markers of inflammation via FFA1 and FFA4 in the mdx mouse model of DMD.

In the present study we investigated the involvement of free fatty acid (FFA) receptors in the anti-inflammatory role of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in dystrophic muscles, by administering FFA blockers in the mdx mouse model of dystrophy. Mdx mice (3 months-old) were treated with fish oil capsules (FDC Vitamins; 0.4 g EPA and 0.2 g DHA; gavage) alone or concomitant to FFA1 and FFA4 blockers (GW1100 and AH7614; i.p.). C57BL/10 mice (3 months-old) and untreated-mdx mice received mineral oil and were used as controls. After 1 month of treatment, plasma markers of myonecrosis (total and cardiac creatine kinase; CK), the levels of FFA1 and FFA4 and of the markers of inflammation, nuclear transcription factor kappa B (NFkB), tumor necrosis factor alpha (TNF-α) and interleukin 1ß (IL-1ß) were analyzed in the diaphragm muscle and heart by western blot. Fish oil significantly reduced total CK, cardiac CK and the levels of NFkB (diaphragm), and of TNF-α and IL-1ß (diaphragm and heart) in mdx. In the dystrophic diaphragm, FFA1 was increased compared to normal. Blockers of FFA1 and FFA4 significantly inhibited the effects of fish oil treatment in both dystrophic muscles. The anti-inflammatory effects of fish oil in dystrophic diaphragm muscle and heart were mediated through FFA1 and FFA4.

No presente estudo investigamos o envolvimento de receptores de ácidos graxos livres (FFA) no efeito anti-inflamatório dos ácidos eicosapentaenoico (EPA) e docosahexaenoico (DHA) em músculos distróficos, administrando bloqueadores de FFA no camundongo mdx, modelo de distrofia. Camundongos mdx (3 meses de idade) foram tratados com cápsulas de óleo de peixe (FDC Vitamins; 0.4 g EPA e 0.2 g DHA; gavagem) ou com cápsulas de óleo de peixe concomitante a bloqueadores de FFA1 e FFA4 (GW1100 e AH7614; i.p.). Camundongos C57BL/10 (3 meses de idade) e camundongos mdx não tratados receberam óleo mineral e serviram de controle. Após 1 mês de tratamento, marcadores plasmáticos de mionecrose (creatina quinase total e cardíaca; CK), os níveis de FFA1 e FFA4 e dos marcadores de inflamação fator de transcrição nuclear kappa B (NFkB, nuclear transcription factor kappa B), fator de necrose tumoral alpha (TNF-α, tumor necrosis factor alpha) e interleucina 1ß (IL-1ß) foram analisados no músculo diafragma e no coração através de western blot. O óleo de peixe reduziu de forma significativa a CK total, CK cardíaca e os níveis de NFkB (diafragma), TNF-α e IL-1ß (diafragma e coração) no mdx. No diafragma distrófico, FFA1 estava aumentado comparado ao normal. Os bloqueadores de FFA1 e FFA4 inibiram de forma significativa os efeitos do tratamento com óleo de peixe em ambos músculos distróficos. Os efeitos anti-inflamatórios do óleo de peixe nos músculos distróficos diafragma e cardíaco foram mediados por FFA1 e FFA4.