Synergistic Antidepressant-like Effects of Biotics and n-3 Polyunsaturated Fatty Acids on Dopaminergic Pathway through the Brain-Gut Axis in Rats Exposed to Chronic Mild Stress.

Probiotics, postbiotics, and n-3 polyunsaturated fatty acids (PUFA) have antidepressant-like effects. However, the underlying mechanisms of the dopaminergic pathway are unclear. The present study investigated the hypothesis that probiotics and postbiotics combined with n-3 PUFA synergistically improve depression by modulating the dopaminergic pathway through the brain-gut axis. Rats were randomly divided into seven groups: non-chronic mild stress (CMS) with n-6 PUFA, and CMS with n-6 PUFA, n-3 PUFA, probiotics, postbiotics, probiotics combined with n-3 PUFA, and postbiotics combined with n-3 PUFA. Probiotics, postbiotics, and n-3 PUFA improved depressive behaviors, decreased blood concentrations of interferon-γ, and interleukin-1ß, and increased the brain and gut concentrations of short chain fatty acids and dopamine. Moreover, probiotics, postbiotics, and n-3 PUFA increased the brain and gut expression of glucocorticoid receptor and tyrosine hydroxylase; brain expression of l-type amino acid transporter 1 and dopamine receptor (DR) D1; and gut expression of DRD2. The expression of phosphorylated protein kinase A/protein kinase A and phosphorylated cAMP response element-binding protein/cAMP response element-binding protein increased in the brain, however, decreased in the gut by the supplementation of probiotics, postbiotics, and n-3 PUFA. There was synergistic effect of probiotics and postbiotics combined with n-3 PUFA on the depressive behaviors and dopaminergic pathway in blood, brain, and gut. Moreover, no significant difference in the dopaminergic pathways between the probiotics and postbiotics was observed. In conclusion, probiotics and postbiotics, combined with n-3 PUFA have synergistic antidepressant-like effects on the dopaminergic pathway through the brain-gut axis in rats exposed to CMS.

Editorial Special Issue: 2022 consortium for trans-pyrenean investigations on obesity and diabetes.

This Special Issue of the Journal of Physiology and Biochemistry contains 7 contributions that have been elaborated in the context of the mini-network "Consortium of Trans-Pyrenean Investigations on Obesity and Diabetes" (CTPIOD), which is on its 19th year of existence. This scientific community, mostly involving research groups from France and Spain, but also open to participants coming from other countries, is focused on investigating the molecular and physiological mechanisms implicated in the development of obesity, diabetes, non-alcoholic fatty liver disease, and other noncommunicable diseases, as well as new preventive and therapeutic strategies. This special issue covers novel nutritional, molecular, and physiological aspects related to these metabolic diseases. Some of these papers emerge from the lectures of the 19th Conference on Trans-Pyrenean Investigations in Obesity and Diabetes, organized by the University of Zaragoza and celebrated in the town of Jaca (Spain) on 17-18th October 2022, and have been prepared in collaboration between different groups of the network. Many lectures were focused on the preventive role of specific fatty acids, dietary phenolic compounds and other phytochemicals against metabolic disorders. Consequently, we encouraged submission of original research in this field for this special issue.

EPA and DHA Enhance CACT Promoter Activity by GABP/NRF2.

Carnitine-acylcarnitine translocase (CACT) is a nuclear-encoded mitochondrial carrier that catalyzes the transfer of long-chain fatty acids across the inner mitochondrial membrane for ß-oxidation. In this study, we conducted a structural and functional characterization of the CACT promoter to investigate the molecular mechanism underlying the transcriptional regulation of the CACT gene by n-3 PUFA, EPA and DHA. In hepatic BRL3A cells, EPA and DHA stimulate CACT mRNA and protein expression. Deletion promoter analysis using a luciferase reporter gene assay identified a n-3 PUFA response region extending from -202 to -29 bp. This region did not contain a response element for PPARα, a well-known PUFA-responsive nuclear receptor. Instead, bioinformatic analysis revealed two highly conserved GABP responsive elements within this region. Overexpression of GABPα and GABPß subunits, but not PPARα, increased CACT promoter activity, more remarkably upon treatment with EPA and DHA. ChIP assays showed that n3-PUFA enhanced the binding of GABPα to the -202/-29 bp sequence. Furthermore, both EPA and DHA induced nuclear accumulation of GABPα. In conclusion, our findings indicate that the upregulation of CACT by n3-PUFA in hepatic cells is independent from PPARα and could be mediated by GABP activation.

Fish Oil Supplementation Mitigates High-Fat Diet-Induced Obesity: Exploring Epigenetic Modulation and Genes Associated with Adipose Tissue Dysfunction in Mice.

This study investigated the effects of fish oil (FO) treatment, particularly enriched with eicosapentaenoic acid (EPA), on obesity induced by a high-fat diet (HFD) in mice. The investigation focused on elucidating the impact of FO on epigenetic modifications in white adipose tissue (WAT) and the involvement of adipose-derived stem cells (ASCs). C57BL/6j mice were divided into two groups: control diet and HFD for 16 weeks. In the last 8 weeks, the HFD group was subdivided into HFD and HFD + FO (treated with FO). WAT was removed for RNA and protein extraction, while ASCs were isolated, cultured, and treated with leptin. All samples were analyzed using functional genomics tools, including PCR-array, RT-PCR, and Western Blot assays. Mice receiving an HFD displayed increased body mass, fat accumulation, and altered gene expression associated with WAT inflammation and dysfunction. FO supplementation attenuated these effects, a potential protective role against HFD-induced obesity. Analysis of H3K27 revealed HFD-induced changes in histone, which were partially reversed by FO treatment. This study further explored leptin signaling in ASCs, suggesting a potential mechanism for ASC dysfunction in the obesity-rich leptin environment of WAT. Overall, FO supplementation demonstrated efficacy in mitigating HFD-induced obesity, influencing epigenetic and molecular pathways, and shedding light on the role of ASCs and leptin signaling in WAT dysfunction associated with obesity.

Effects of short-term supplementation with DHA-enriched phosphatidylcholine and phosphatidylserine on lipid profiles in the brain and liver of n-3 PUFA-deficient mice in early life after weaning.

BACKGROUND: Lack of n-3 polyunsaturated fatty acids during the period of maternity drastically lowers the docosahexaenoic acid (DHA) level in the brain of offspring and studies have demonstrated that different molecular forms of DHA are beneficial to brain development. The aim of this study was to investigate the effect of short-term supplementation with DHA-enriched phosphatidylserine (PS) and phosphatidylcholine (PC) on DHA levels in the liver and brain of congenital n-3-deficient mice. RESULTS: Dietary supplementation with DHA significantly changed the fatty acid composition of various phospholipid molecules in the cerebral cortex and liver while DHA-enriched phospholipid was more effective than DHA triglyceride (TG) in increasing brain and liver DHA. Both DHA-PS and DHA-PC could effectively increase the DHA levels, but DHA in the PS form was superior to PC in the contribution of DHA content in the brain ether-linked PC (ePC) and liver lyso-phosphatidylcholine molecular species. DHA-PC showed more significant effects on the increase of DHA in liver TG, PC, ePC, phosphatidylethanolamine (PE) and PE plasmalogen (pPE) molecular species and decreasing the arachidonic acid level in liver PC plasmalogen, ePC, PE and pPE molecular species compared with DHA-PS. CONCLUSION: The effect of dietary interventions with different molecular forms of DHA for brain and liver lipid profiles is different, which may provide theoretical guidance for dietary supplementation of DHA for people. © 2024 Society of Chemical Industry.

Enhancing Endothelial Function with Nutrient-Enriched Table Hen Eggs: A Randomized Study in Patients Recovering from Acute Coronary Syndrome.

Purpose: This study investigated the effect of consumption of table eggs enriched with n-3 polyunsaturated fatty acids (n-3 PUFA), lutein, vitamin E and selenium on microvascular function, oxidative stress and inflammatory mediators in patients after acute coronary syndrome (ACS). Patients and Methods: In a prospective, randomized, interventional, double-blind clinical trial, ACS patients were assigned to either the Nutri4 (N=15, mean age: 57.2 ± 9.2 years), or the Control group (N=13; mean age 56.8 ± 9.6 years). The Nutri4 group consumed three enriched hen eggs daily for three weeks, providing approximately 1.785 mg of vitamin E, 0.330 mg of lutein, 0.054 mg of selenium and 438 mg of n-3 PUFAs. Biochemical parameters, including serum lipids, liver enzymes, nutrient concentrations, serum antioxidant enzyme activity (catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD)), and markers of oxidative stress (thiobarbituric acid reactive substances (TBARS) and ferric reducing ability (FRAP)), were assessed before and after the dietary interventions. Additionally, arterial blood pressure, heart rate, body composition, fluid status, anthropometric measurements, and skin microvascular blood flow responses to various stimuli (postocclusive reactive hyperemia (PORH), acetylcholine- (Ach ID), and sodium nitroprusside- (SNP ID)) were measured using laser Doppler flowmetry (LDF) throughout the study. Results: The intake of Nutri4 eggs led to a significant reduction in LDL cholesterol levels, while the levels of total cholesterol remained within the established reference values. Consuming Nutri4 eggs resulted in a 12.7% increase in serum vitamin E levels, an 8.6% increase in selenium levels, and demonstrated a favorable impact on microvascular reactivity, as evidenced by markedly improved PORH and ACh ID. Nutri4 eggs exerted a significant influence on the activity of GPx and SOD, with no observed changes in TBARS or FRAP values. Conclusion: The consumption of Nutri4 eggs positively influenced microvascular function in individuals with ACS, without eliciting adverse effects on oxidative stress.

Current Insights into the Effects of Dietary α-Linolenic Acid Focusing on Alterations of Polyunsaturated Fatty Acid Profiles in Metabolic Syndrome.

The plant-derived α-linolenic acid (ALA) is an essential n-3 acid highly susceptible to oxidation, present in oils of flaxseeds, walnuts, canola, perilla, soy, and chia. After ingestion, it can be incorporated in to body lipid pools (particularly triglycerides and phospholipid membranes), and then endogenously metabolized through desaturation, elongation, and peroxisome oxidation to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with a very limited efficiency (particularly for DHA), beta-oxidized as an energy source, or directly metabolized to C18-oxilipins. At this moment, data in the literature about the effects of ALA supplementation on metabolic syndrome (MetS) in humans are inconsistent, indicating no effects or some positive effects on all MetS components (abdominal obesity, dyslipidemia, impaired insulin sensitivity and glucoregulation, blood pressure, and liver steatosis). The major effects of ALA on MetS seem to be through its conversion to more potent EPA and DHA, the impact on the n-3/n-6 ratio, and the consecutive effects on the formation of oxylipins and endocannabinoids, inflammation, insulin sensitivity, and insulin secretion, as well as adipocyte and hepatocytes function. It is important to distinguish the direct effects of ALA from the effects of EPA and DHA metabolites. This review summarizes the most recent findings on this topic and discusses the possible mechanisms.

n-3 fatty acids and the risk of atrial fibrillation, review.

Atrial fibrillation (AF) is the most frequent type of cardiac arrhythmia that affects over six million individuals in Europe. The incidence and prevalence of AF rises with age, and often occurs after cardiac surgery. Other risk factors correlated with AF comprise high blood pressure, diabetes mellitus, left atrial enlargement, ischemic heart disease, and congestive heart failure. Considering the high prevalence of AF in aging societies, strategies to prevent serious complications, such as stroke or heart failure, are important because they are correlated with high morbidity and mortality. The supplementation of sea-derived n-3 polyunsaturated fatty acids (PUFA) is widely discussed in this context, but the results of experimental and observational studies are in contrast to randomized placebo-controlled intervention trials (RCTs). Specifically, larger placebo-controlled n-3 PUFA supplementation studies with long follow-up showed a dose-dependent rise in incident AF. Daily n-3 PUFA doses of ≥1 g/d are correlated with a 50 % increase in AF risk, whereas a daily intake of <1 g/d causes AF in only 12 %. Individuals with a high cardiovascular risk (CVD) risk and high plasma-triglycerides seem particularly prone to develop AF upon n-3 PUFA supplementation. Therefore, we should exercise caution with n-3 PUFA supplementation especially in patients with higher age, CVD, hypertriglyceridemia or diabetes. In summary, existing data argue against the additive intake of n-3 PUFA for preventative purposes because of an incremental AF risk and lacking CVD benefits. However, more clinical studies are required to disentangle the discrepancy between n-3 PUFA RCTs and observational studies showing a lower CVD risk in individuals who regularly consume n-3 PUFA-rich fish.

Molecular Mechanisms Associated with the Inhibitory Role of Long Chain n-3 PUFA in Colorectal Cancer.

Colorectal cancer (CRC) is the third leading cause of cancer-related death in the world. Multiple evidence suggests that there is an association between excess fat consumption and the risk of CRC. The long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential for human health, and both in vitro and in vivo studies have shown that these fatty acids can prevent CRC development through various molecular mechanisms. These include the modulation of arachidonic acid (AA) derived prostaglandin synthesis, alteration of growth signaling pathways, arrest of the cell cycle, induction of cell apoptosis, suppression of angiogenesis and modulation of inflammatory response. Human clinical studies found that LC n-3 PUFA combined with chemotherapeutic agents can improve the efficacy of treatment and reduce the dosage of chemotherapy and associated side effects. In this review, we discuss comprehensively the anti-cancer effects of LC n-3 PUFA on CRC, with a main focus on the underlying molecular mechanisms.

Interaction of Vitamin D Supplements and Marine n-3 Fatty Acids on Digestive Tract Cancer Prognosis.

A meta-analysis suggested that marine n-3 polyunsaturated fatty acids (PUFAs), e.g., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), might reduce cancer mortality. However, a randomized clinical trial of marine n-3 PUFA and vitamin D supplementation failed to verify this benefit. This study aimed to investigate the potential interaction between vitamin D supplementation and serum EPA and DHA levels. This post hoc analysis of the AMATERASU trial (UMIN000001977), a randomized controlled trial (RCT), included 302 patients with digestive tract cancers divided into two subgroups stratified by median serum levels of EPA + DHA into higher and lower halves. The 5-year relapse-free survival (RFS) rate was significantly higher in the higher half (80.9%) than the lower half (67.8%; hazard ratio (HR), 2.15; 95% CI, 1.29-3.59). In the patients in the lower EPA + DHA group, the 5-year RFS was significantly higher in the vitamin D (74.9%) than the placebo group (49.9%; HR, 0.43; 95% CI, 0.24-0.78). Conversely, vitamin D had no effect in the higher half, suggesting that vitamin D supplementation only had a significant interactive effect on RFS in the lower half (p for interaction = 0.03). These results suggest that vitamin D supplementation may reduce the risk of relapse or death by interacting with marine n-3 PUFAs.

Krill Oil and Its Bioactive Components as a Potential Therapy for Inflammatory Bowel Disease: Insights from In Vivo and In Vitro Studies.

Krill oil is extracted from krill, a small crustacean in the Antarctic Ocean. It has received growing attention because of krill oil's unique properties and diverse health benefits. Recent experimental and clinical studies suggest that it has potential therapeutic benefits in preventing the development of a range of chronic conditions, including inflammatory bowel disease (IBD). Krill oil is enriched with long-chain n-3 polyunsaturated fatty acids, especially eicosapentaenoic and docosahexaenoic acids, and the potent antioxidant astaxanthin, contributing to its therapeutic properties. The possible underlying mechanisms of krill oil's health benefits include anti-inflammatory and antioxidant actions, maintaining intestinal barrier functions, and modulating gut microbiota. This review aims to provide an overview of the beneficial effects of krill oil and its bioactive components on intestinal inflammation and to discuss the findings on the molecular mechanisms associated with the role of krill oil in IBD prevention and treatment.

The influence of n-3 polyunsaturated fatty acids on cognitive function in individuals without dementia: a systematic review and dose-response meta-analysis.

BACKGROUND: Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been suggested as a cognitive enhancing agent, though their effect is doubtful. We aimed to examine the effect of n-3 PUFA on the cognitive function of middle-aged or older adults without dementia. METHODS: We reviewed randomized controlled trials of individuals aged 40 years or older. We systematically searched PubMed/MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Library databases. We used the restricted cubic splines model for non-linear dose-response meta-analysis in terms of the standardized mean difference with 95% confidence intervals. RESULTS: The current meta-analysis on 24 studies (n 9660; follow-up 3 to 36 months) found that the beneficial effect on executive function demonstrates an upward trend within the initial 12 months of intervention. This effect is prominently observed with a daily intake surpassing 500 mg of n-3 PUFA and up to 420 mg of eicosapentaenoic acid (EPA). Furthermore, these trends exhibit heightened significance in regions where the levels of blood docosahexaenoic acid (DHA) + EPA are not very low. CONCLUSIONS: Supplementation of n-3 PUFA may confer potential benefits to executive function among the middle-aged and elderly demographic, particularly in individuals whose dietary DHA + EPA level is not substantially diminished.

n-3 enriched Fish oil diet enhanced intestinal barrier integrity in broilers after Eimeria infection.

Coccidiosis caused by Eimeria spp. results in substantial economic losses in the poultry industry. The objective of this study was to investigate the effects of dietary supplementation with n-3 polyunsaturated fatty acids-enriched fish oil on growth performance, intestinal barrier integrity, and intestinal immune response of broilers challenged with Eimeria spp. A total of 576 fourteen-day-old broilers were randomly assigned in a completely randomized design with a 3 × 2 factorial arrangement, comprising 2 diets supplemented with either 5% fish oil or 5% soybean oil, and 3 Eimeria spp. infection levels: a nonchallenge control, a low dose of Eimeria challenge, and a high challenge dose. The results of the study revealed significant interactions between diet and Eimeria challenge to parameters of gut barrier integrity and feed intake. A significant interaction was observed in feed intake between 5 and 8 d postinfection (DPI), where the fish oil groups exhibited a higher amount of feed intake compared to the soybean oil diet groups after coccidiosis infection. The effects of the fish oil diet resulted in enhanced gut barrier integrity, as evidenced by a trend of decreased gastrointestinal leakage and a lower mean of small intestine lesion scores after Eimeria challenge. Additionally, significant interactions were noted between Eimeria spp. challenge and diet regarding jejunal crypt depth. The positive impact of the fish oil diet was particularly noticeable with the high Eimeria challenge dose. Overall, these findings underscore the relationship between the fish oil diet and Eimeria challenge on broiler chicken intestinal health. Dietary supplementation of fish oil has the potential to maintain small intestine barrier integrity with severe Eimeria infection conditions.

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.

Long chain n-3 polyunsaturated fatty acid intake across the life span for cardiovascular disease prevention in women.

Cardiovascular diseases (CVDs) are a major health concern for women. Historically there has been a misconception that men are at greater risk because CVD tends to occur earlier in life compared to women. Clinical guidelines for prevention of heart disease are currently the same for both sexes, but accumulating evidence demonstrates that risk profiles diverge. In fact, several CVD risk factors confer an even greater risk in women relative to men, including high blood pressure, obesity, diabetes and raised triglycerides. Furthermore, many female-specific CVD risk factors exist, including early menarche, pregnancy complications, polycystic ovary syndrome, reproductive hormonal treatments and menopause. Little is known about how diet interacts with CVD risk factors at various stages of a woman's life. Long chain (LC) n-3 polyunsaturated fatty acid (PUFA) intakes are a key dietary factor that may impact risk of CVD throughout the life course differentially in men and women. Oestrogen enhances conversion of the plant n-3 PUFA, alpha-linolenic acid, to LCn-3 PUFA. Increasing the frequency of oily fish consumption or LCn-3 PUFA supplementation may be important for reducing coronary risk during the menopausal transition, during which time oestrogen levels decline and the increase in CVD risk factors is accelerated. Women are under-represented in the evidence base for CVD prevention following LC n-3 PUFA supplementation. Therefore it is not clear whether there are sex differences in response to treatment. Furthermore, there is a lack of evidence on optimal intakes of LC n-3 PUFA across the lifespan for CVD prevention in women.

Experimental evidence that EPA and DHA are dietary requirements in a migratory shorebird, but they do not affect muscle oxidative capacity.

Dietary n-3 long chain polyunsaturated fatty acids (LCPUFAs) are hypothesized to be natural doping agents in migratory shorebirds, enabling prolonged flight by increasing membrane fluidity and oxidative capacity of the flight muscles. Animals can obtain n-3 LCPUFAs from the diet or by conversion of dietary α-linolenic acid, 18:3 n-3. However, the capacity to meet n-3 LCPUFA requirements from 18:3 n-3 varies among species. Direct tests of muscle oxidative enhancement and fatty acid conversion capacity are lacking in marine shorebirds that evolved eating diets rich in n-3 LCPUFAs. We tested whether the presence and type of dietary fatty acids influence the fatty acid composition and flight muscle oxidative capacity in western sandpipers (Calidris mauri). Sandpipers were fed diets low in n-3 PUFAs, high in 18:3 n-3, or high in n-3 LCPUFAs. Dietary fatty acid composition was reflected in multiple tissues, and low intake of n-3 LCPUFAs decreased the abundance of these fatty acids in all tissues, even with a high intake of 18:3 n-3. This suggests that 18:3 n-3 cannot replace n-3 LCPUFAs, and dietary n-3 LCPUFAs are required for sandpipers. Flight muscle indicators of enzymatic oxidative capacity and regulators of lipid metabolism did not change. However, the n-3 LCPUFA diet was associated with increased FAT/CD36 mRNA expression, potentially benefitting fatty acid transport during flight. Our study suggests that flight muscle lipid oxidation is not strongly influenced by n-3 PUFA intake. The type of dietary n-3 PUFA strongly influences the abundance of n-3 LCPUFAs in the body and could still impact whole-animal performance.

DHA and EPA in Sickle Cell Disease Favor Clinical Improvement and Contribute to Better Quality of Life: A Qualitative Systematic Review.

BACKGROUND: Sickle cell disease is a severe genetic disorder, and searching for therapeutic strategies is indispensable for prolonged and improved life for people affected by this condition. OBJECTIVE: This qualitative systematic review aimed to highlight the therapeutic potential of omega- 3 (n-3) in people with sickle cell disease. METHODS: The search was performed by combining sickle cell disease and n-3 descriptors in DeCS/ MeSH databases, including Scopus, PubMed, ScienceDirect, Web of Science, and Virtual Health Library. The risk of bias assessment in the primary studies was performed using the Cochrane risk of bias tool for randomized controlled trials. The evidence quality was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. RESULTS: From the 187 records identified, seven were selected for data collection. Based on the evidence, n-3 supplementation contributes to lower activation of pro-inflammatory biomarkers, improves the concentration of docosahexaenoic and eicosapentaenoic acids in the erythrocyte membrane, provides better hemostatic response, and helps in vaso-occlusive crisis, pain episodes, and hospitalization reduction. CONCLUSION: The findings suggest that n-3 adjuvant therapy favors the clinical and general aspects of people with sickle cell disease.

Nutrient composition of different energy-restricted diets determines plasma endocannabinoid profiles and adipose tissue DAGL-α expression; a 12-week randomized controlled trial in subjects with abdominal obesity.

The endocannabinoid system (ECS) is dysregulated during obesity and metabolic disorders. Weight loss favours the re-establishment of ECS homeostatic conditions, but also the fatty acid composition of the diet can modulate endocannabinoid profiles. However, the combined impact of nutrient quality and energy restriction on the ECS remains unclear. In this 12 weeks randomized controlled trial, men and women (40-70 years) with obesity (BMI: 31.3 ± 3.5 kg/ m2) followed either a low nutrient quality 25% energy-restricted (ER) diet (n=39) high in saturated fats and fructose, or a high nutrient quality ER diet (n=34) amongst others enriched in n-3 polyunsaturated fatty acids (PUFAs) or kept their habitual diet (controls). Profiles of plasma- and adipose N-acylethanolamines and mono-acyl glycerol esters were quantified using LC-MS/MS. Gene expression of ECS-related enzymes and receptors was determined in adipose tissue. Measurements were performed under fasting conditions before and after 12 weeks. Our results showed that plasma level of the DHA-derived compound docosahexaenoylethanolamide (DHEA) was decreased in the low nutrient quality ER diet (P<0.001) compared with the high nutrient quality ER diet, whereas anandamide (AEA) and arachidonoylglycerol (2-AG) levels were unaltered. However, adipose tissue gene expression of the 2-AG synthesizing enzyme diacylglycerol lipase alpha (DAGL-α) was increased following the low nutrient quality ER diet (P<.009) and differed upon intervention with both other diets. Concluding, nutrient quality of the diet affects N-acylethanolamine profiles and gene expression of ECS-related enzymes and receptors even under conditions of high energy restriction in abdominally obese humans. ClinicalTrials.gov NCT02194504.

High-Fat Diet-Induced Obesity Increases Brain Mitochondrial Complex I and Lipoxidation-Derived Protein Damage.

Obesity is a risk factor for highly prevalent age-related neurodegenerative diseases, the pathogenesis of whichinvolves mitochondrial dysfunction and protein oxidative damage. Lipoxidation, driven by high levels of peroxidizable unsaturated fatty acids and low antioxidant protection of the brain, stands out as a significant risk factor. To gain information on the relationship between obesity and brain molecular damage, in a porcine model of obesity we evaluated (1) the level of mitochondrial respiratory chain complexes, as the main source of free radical generation, by Western blot; (2) the fatty acid profile by gas chromatography; and (3) the oxidative modification of proteins by mass spectrometry. The results demonstrate a selectively higher amount of the lipoxidation-derived biomarker malondialdehyde-lysine (MDAL) (34% increase) in the frontal cortex, and positive correlations between MDAL and LDL levels and body weight. No changes were observed in brain fatty acid profile by the high-fat diet, and the increased lipid peroxidative modification was associated with increased levels of mitochondrial complex I (NDUFS3 and NDUFA9 subunits) and complex II (flavoprotein). Interestingly, introducing n3 fatty acids and a probiotic in the high-fat diet prevented the observed changes, suggesting that dietary components can modulate protein oxidative modification at the cerebral level and opening new possibilities in neurodegenerative diseases' prevention.

Fish oil supplement use modifies the relationship between dietary oily fish intake and plasma n-3 PUFA levels: an analysis of the UK Biobank.

Observational evidence linking dietary n-3 PUFA intake and health outcomes is limited by a lack of robust validation of dietary intake using blood n-3 PUFA levels and potential confounding by fish oil supplement (FOS) use. We investigated the relationship between oily fish intake, FOS use and plasma n-3 PUFA levels in 121 650 UK Biobank (UKBB) participants. Ordinal logistic regression models, adjusted for clinical and lifestyle factors, were used to quantify the contribution of dietary oily fish intake and FOS use to plasma n-3 PUFA levels (measured by NMR spectroscopy). Oily fish intake and FOS use were reported by 38 % and 31 % of participants, respectively. Increasing oily fish intake was associated with a higher likelihood of FOS use (P < 0·001). Oily fish intake ≥ twice a week was the strongest predictor of high total n-3 PUFA (OR 6·7 (95 % CI 6·3, 7·1)) and DHA levels (6·6 (6·3, 7·1). FOS use was an independent predictor of high plasma n-3 PUFA levels (2·0 (2·0, 2·1)) with a similar OR to that associated with eating oily fish < once a week (1·9 (1·8, 2·0)). FOS use was associated with plasma n-3 PUFA levels that were similar to individuals in the next highest oily fish intake category. In conclusion, FOS use is more common in frequent fish consumers and modifies the relationship between oily fish intake and plasma n-3 PUFA levels in UKBB participants. If unaccounted for, FOS use may confound the relationship between dietary n-3 PUFA intake, blood levels of n-3 PUFAs and health outcomes.