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.

Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Induced Carcinogenesis and Tumorigenesis by Omega-3 Fatty Acids in Mice In Vivo.

Lung cancer is the leading cause of cancer death worldwide. Polycyclic aromatic hydrocarbons (PAHs) are metabolized by the cytochrome P450 (CYP)1A and 1B1 to DNA-reactive metabolites, which could lead to mutations in critical genes, eventually resulting in cancer. Omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial against cancers. In this investigation, we elucidated the mechanisms by which omega-3 fatty acids EPA and DHA will attenuate PAH-DNA adducts and lung carcinogenesis and tumorigenesis mediated by the PAHs BP and MC. Adult wild-type (WT) (A/J) mice, Cyp1a1-null, Cyp1a2-null, or Cyp1b1-null mice were exposed to PAHs benzo[a]pyrene (BP) or 3-methylcholanthrene (MC), and the effects of omega-3 fatty acid on PAH-mediated lung carcinogenesis and tumorigenesis were studied. The major findings were as follows: (i) omega-3 fatty acids significantly decreased PAH-DNA adducts in the lungs of each of the genotypes studied; (ii) decreases in PAH-DNA adduct levels by EPA/DHA was in part due to inhibition of CYP1B1; (iii) inhibition of soluble epoxide hydrolase (sEH) enhanced the EPA/DHA-mediated prevention of pulmonary carcinogenesis; and (iv) EPA/DHA attenuated PAH-mediated carcinogenesis in part by epigenetic mechanisms. Taken together, our results suggest that omega-3 fatty acids have the potential to be developed as cancer chemo-preventive agents in people.

Omega-3 polyunsaturated fatty acid derived lipid mediators: a comprehensive update on their application in anti-cancer drug discovery.

INTRODUCTION: ω-3 Polyunsaturated fatty acids (PUFAs) have a range of health benefits, including anticancer activity, and are converted to lipid mediators that could be adapted into pharmacological strategies. However, the stability of these mediators must be improved, and they may require formulation to achieve optimal tissue concentrations. AREAS COVERED: Herein, the author reviews the literature around chemical stabilization and formulation of ω-3 PUFA mediators and their application in anticancer drug discovery. EXPERT OPINION: Aryl-urea bioisosteres of ω-3 PUFA epoxides that killed cancer cells targeted the mitochondrion by a novel dual mechanism: as protonophoric uncouplers and as inhibitors of electron transport complex III that activated ER-stress and disrupted mitochondrial integrity. In contrast, aryl-ureas that contain electron-donating substituents prevented cancer cell migration. Thus, aryl-ureas represent a novel class of agents with tunable anticancer properties. Stabilized analogues of other ω-3 PUFA-derived mediators could also be adapted into anticancer strategies. Indeed, a cocktail of agents that simultaneously promote cell killing, inhibit metastasis and angiogenesis, and that attenuate the pro-inflammatory microenvironment is a novel future anticancer strategy. Such regimen may enhance anticancer drug efficacy, minimize the development of anticancer drug resistance and enhance outcomes.

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.

Differential Effects of n-3 and n-6 Polyunsaturated Fatty Acids on Placental and Embryonic Growth and Development in Diabetic Pregnant Mice.

The present study aimed to investigate the differential effects of n-3 and n-6 polyunsaturated fatty acids (PUFAs) on placental and embryonic development. Pregnant mice were assigned to five groups: healthy control (HC), diabetes mellitus control (DMC), diabetes + low-dose n-3 PUFA (Ln-3), diabetes + high-dose n-3 PUFA (Hn-3), and diabetes + n-6 PUFA (n-6). On E12.5d, the Hn-3 group, but not the n-6 group, had a higher placenta weight. The weight ratio of embryo to placenta in the n-6 group was significantly lower than in the Hn-3 group but higher than in the DMC group. The Hn-3 group had significantly higher protein levels of VEGF, IGF-1, and IGFBP3, while the n-6 group had lower VEGF than the DMC group. Compared with the DMC group, embryonic Cer-16:0 was significantly higher in the Hn-3 group, while embryonic PC (36:6), PC (38:7), and PE (40:7) were significantly lower in the n-6 group. The embryo and placenta weights were positively correlated with placental VEGF, IGFBP3, and embryonic Cer-16:0, and they were negatively correlated with embryonic PC (36:6) and PE (40:7). The weight ratio of embryo to placenta was negatively correlated with embryonic PC (36:6). In addition, embryonic Cer-16:0 was positively correlated with placental VEGF and IGFBP3. In conclusion, n-3 PUFA and n-6 PUFA improved placental and embryonic growth through different mechanisms.

Gene and lncRNA Profiling of ω3/ω6 Polyunsaturated Fatty Acid-Exposed Human Visceral Adipocytes Uncovers Different Responses in Healthy Lean, Obese and Colorectal Cancer-Affected Individuals.

Colorectal cancer (CRC) is a major life-threatening disease, being the third most common cancer and a leading cause of death worldwide. Enhanced adiposity, particularly visceral fat, is a major risk factor for CRC, and obesity-associated alterations in metabolic, inflammatory and immune profiles in visceral adipose tissue (VAT) strongly contribute to promoting or sustaining intestinal carcinogenesis. The role of diet and nutrition in obesity and CRC has been extensively demonstrated, and AT represents the main place where diet-induced signals are integrated. Among the factors introduced with diet and processed or enriched in AT, ω3/ω6 polyunsaturated fatty acids (PUFAs) are endowed with pro- or anti-inflammatory properties and have been shown to exert either promoting or protective roles in CRC. In this study, we investigated the impact of ex vivo exposure to the ω3 and ω6 PUFAs docosahexaenoic and arachidonic acids on VAT adipocyte whole transcription in healthy lean, obese and CRC-affected individuals. High-throughput sequencing of protein-coding and long non-coding RNAs allowed us to identify specific pathways and regulatory circuits controlled by PUFAs and highlighted an impaired responsiveness of obese and CRC-affected individuals as compared to the strong response observed in healthy lean subjects. This further supports the role of healthy diets and balanced ω3/ω6 PUFA intake in the primary prevention of obesity and cancer.

Overview of alkyl quercetin lipophenol synthesis and its protective effect against carbonyl stress involved in neurodegeneration.

Oxidative stress and carbonyl stress resulting from the toxicity of small aldehydes are part of the detrimental mechanisms leading to neuronal cell loss involved in the progression of neurodegenerative diseases such as Alzheimer's disease. Polyunsaturated alkylated lipophenols represent a new class of hybrid molecules that combine the health benefits of anti-inflammatory omega-3 fatty acids with the anti-carbonyl and oxidative stress (anti-COS) properties of (poly)phenols in a single pharmacological entity. To investigate the therapeutic potential of quercetin-3-docosahexaenoic acid-7-isopropyl lipophenol in neurodegenerative diseases, three synthetic pathways using chemical or chemo-enzymatic strategies were developed to access milligram or gram scale quantities of this alkyl lipophenol. The protective effect of quercetin-3-DHA-7-iPr against cytotoxic concentrations of acrolein (a carbonyl stressor) was assessed in human SHSY-5Y neuroblastoma cells to underscore its ability to alleviate harmful mechanisms associated with carbonyl stress in the context of neurodegenerative diseases.

Curcumin and omega-3 polyunsaturated fatty acids as bioactive food components with synergistic effects on Alzheimer's disease.

Curcumin and omega-3 polyunsaturated fatty acids (ω-3 PUFA) are multifunctional compounds which play an important role in Alzheimer's disease (AD) and little has been addressed about the role of these two compounds together in the progression of the disease. There is evidence of the beneficial effect of combined administration of ω-3 PUFA and other dietary supplements such as vitamins and polyphenols in the prevention of AD, although much remains to be understood about their possible complementary or synergistic activity. Therefore, the objective of this work is to review the research focused on studying the effect and mechanisms of action of curcumin, ω-3 PUFA, and the combination of these nutraceutical compounds, particularly on AD, and to integrate the possible ways in which these compounds can potentiate their effect. The most important pathophysiologies that manifest in AD will be addressed, in order to have a better understanding of the mechanisms of action through which these bioactive compounds exert a neuroprotective effect.

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.

Phospholipid-rich krill oil promotes intestinal health by strengthening beneficial gut microbial interactions in an infectious colitis model.

Krill oil (KO) is rich in bioactive ingredients including phospholipids, omega-3 fatty acids, and astaxanthin. While health benefits and roles of KO in modulating lipid metabolism are well documented, its ability to alleviate symptoms related to infectious colitis and modulate gut microbial interactions is still largely unknown. Here we used a multi-omics approach, including transcriptome, microbiome, and metabolome analyses, to understand how KO mediates gut microbial interactions and promotes epithelial healing in an infectious colitis model. KO reversed the infection-induced intestinal hyperplasia to baseline. KO dampened intestinal inflammation via multiple targets, mediating several proinflammatory pathways, including IL17 signaling, and reducing luminal histamine levels. KO supplementation enriched butyrate-producing bacteria, including Roseburia and Clostridium, and strengthened beneficial microbial interactions in the gut microbial community. Supplementation with phospholipid-rich KO also increased microbial phylogenetic diversity. KO enhanced mucosal barrier function by increasing the production of Muc6 and the antimicrobial peptide, Leap2. KO played an active role during epithelial healing by inhibiting the expression of granzyme K while increasing the expression of a colitis protective factor, Dclk1. Together, our findings demonstrate that KO rich in omega-3 phospholipids can play a protective role in infectious colitis and should be considered a dietary option for promoting gut health.

Oleaginous Microbial Lipids' Potential in the Prevention and Treatment of Neurological Disorders.

The products of oleaginous microbes, primarily lipids, have gained tremendous attention for their health benefits in food-based applications as supplements. However, this emerging biotechnology also offers a neuroprotective treatment/management potential for various diseases that are seldom discussed. Essential fatty acids, such as DHA, are known to make up the majority of brain phospholipid membranes and are integral to cognitive function, which forms an important defense against Alzheimer's disease. Omega-3 polyunsaturated fatty acids have also been shown to reduce recurrent epilepsy seizures and have been used in brain cancer therapies. The ratio of omega-3 to omega-6 PUFAs is essential in maintaining physiological function. Furthermore, lipids have also been employed as an effective vehicle to deliver drugs for the treatment of diseases. Lipid nanoparticle technology, used in pharmaceuticals and cosmeceuticals, has recently emerged as a biocompatible, biodegradable, low-toxicity, and high-stability means for drug delivery to address the drawbacks associated with traditional medicine delivery methods. This review aims to highlight the dual benefit that lipids offer in maintaining good health for disease prevention and in the treatment of neurological diseases.

Potential nutritional strategies to prevent and reverse sarcopenia in aging process: Role of fish oil-derived ω-3 polyunsaturated fatty acids, wheat oligopeptide and their combined intervention.

INTRODUCTION: Nutritional support is potentially considered an essential step to prevent muscle loss and enhance physical function in older adults. OBJECTIVES: This study aimed to assess the role of potential nutritional strategies, i.e., fish oil-derived ω-3 polyunsaturated fatty acids (PUFAs), wheat oligopeptide and their combined intervention, in preventing and reversing sarcopenia in aging process. METHODS: One hundred 25-month-old Sprague-Dawley rats were randomly divided into 10 groups, and 10 newly purchased 6-month-old rats were included in young control group (n = 10). Fish oil (200, 400 or 800 mg/kg body weight), wheat oligopeptide (100, 200 or 400 mg/kg body weight), fish oil + wheat oligopeptide (800 + 100, 400 + 200 or 200 + 400 mg/kg body weight) or the equal volume of solvent were administered daily by gavage for 10 weeks. The effects of these interventions on natural aging rats were evaluated. RESULTS: All intervention groups had a significant increase in muscle mass and grip strength and reduction in perirenal fat weight when compared to the aged control group (P < 0.05). The results of biochemical parameters, magnetic resonance imaging, proteomics and western blot suggested that the combination of wheat oligopeptide and fish oil-derived ω-3 PUFA, especially group WFM 2 (400 + 200 mg/kg body weight fish oil + wheat oligopeptide), was found to be more effective against aging-associated muscle loss than single intervention. Additionally, the interventions ameliorated fatty infiltration, muscle atrophy, and congestion in the intercellular matrix, and inflammatory cell infiltration in muscle tissue. The interventions also improved oxidative stress, anabolism, hormone levels, and inflammatory levels of skeletal muscle. CONCLUSIONS: The combination of fish oil-derived ω-3 PUFA and wheat oligopeptide was found to be a promising nutritional support to prevent and reverse sarcopenia. The potential mechanism involved the promotion of protein synthesis and muscle regeneration, as well as the enhancement of muscle strength.

A diet rich in omega-3 fatty acid improves periodontitis and tissue destruction by MMP2- and MMP9-linked inflammation in a murine model.

Periodontitis is an oral-cavity inflammatory disease and is the principal cause associated with tooth loss. Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) are important proteases involved in periodontal tissue destruction. The omega-3 polyunsaturated fatty acids (ω-3 PUFA) have been demonstrated to possess immunoregulatory properties in periodontitis. The aim of the study was to investigate the effects of ω-3 PUFA on inflammation and on the expression of MMP-2 and -9 in a murine periodontitis model. Twenty-four male C57BL/6 mice were divided into control mice (Control), control mice treated with ω-3 PUFA (O3), mice with periodontitis (P), and mice with periodontitis treated with ω-3 PUFA (P + O3). ω-3 PUFA were administered orally once a day for 70 days. Periodontitis in mice was induced by Porphyromonas gingivalis-infected ligature placement around the second maxillary molar. The mice were sacrificed, and blood and maxillary samples were collected. Flow cytometry was used to quantify tumor necrosis factor-alpha (TNFα), interleukin (IL)-2, IL-4, IL-5, and interferon-gamma. Histologic analysis and immunohistochemistry for MMP-2 and -9 were performed. The data were statistically evaluated using analysis of variance (ANOVA) and the Tukey post hoc test. Histological analysis showed that ω-3 PUFA supplementation prevented inflammation and tissue destruction and revealed that bone destruction was more extensive in the P group than in the P + O3 group (p < 0.05). Also, it decreased the serum expressions of TNFα and IL-2 and the tissue expression of MMP-2 and -9 in the periodontitis-induced model (p < 0.05). ω-3 PUFA supplementation prevented alveolar bone loss and periodontal destruction, probably by decreasing the expression of MMP-2 and MMP-9 and its immunoregulatory properties.

Fish oil omega-3 Fatty Acids Alleviate Postoperative delirium-like Behavior in aged mice by Attenuating Neuroinflammation and Oxidative Stress.

Postoperative delirium (POD) is a common and serious neuropsychiatric syndrome among older patients, and lacks effective therapies. Omega-3 fatty acids, possessing anti-inflammatory and antioxidant properties, have shown potent neuroprotective effects in several diseases. The present study investigated whether omega-3 fatty acids could exert a neuroprotective role against POD in aged mice. A mouse model of POD was established to explore the role of omega-3 fatty acids in laparotomy-induced delirium-like behavior by evaluating systemic inflammatory changes, neuroinflammation, oxidative stress, and behavior at different time points in aged mice. Oral gavage with omega-3 fatty acids (300 mg/kg) for 3 weeks before surgery significantly attenuated anesthesia/surgery-induced POD-like behavior and the accumulation of proinflammatory cytokines from the peripheral blood in aged mice. Moreover, it also remarkably mitigated neuroinflammation and the oxidative stress response (malondialdehyde [MDA] and superoxide dismutase [SOD]) in the prefrontal cortex and hippocampus of surgical mice. Our findings provided evidence that pretreatment with omega-3 fatty acids may play a vital role in the treatment of POD through mechanisms involving its anti-inflammatory and antioxidant effects, which may be a promising prevention strategy for POD in aged patients.

The Effects of Omega-3 Fatty Acids Supplementation on Inflammatory Factors in Cancer Patients: A Systematic Review and Dose-Response Meta-Analysis of Randomized Clinical Trials.

Until now, no study evaluated the impact of optimum intake of omega-3 fatty acids on inflammatory factors. We aimed to investigate the dose-dependent effects of omega-3 fatty acids supplementation on inflammatory factors in cancer patients. PubMed, Scopus and ISI Web of Science were searched until July 2022 to find randomized controlled trials (RCTs) for examining the efficacy of omega-3 fatty acids on inflammatory factors. Our primary outcomes were interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and albumin. The results of 33 trials (2068 participants) revealed that each 1 g/day omega-3 fatty acids (oral/enteral) significantly reduced IL-6 (SMD: -1.17 pg/ml; 95% CI: -1.78, -0.55; p < 0.001; GRADE = moderate), and TNF-α (SMD: -2.15 pg/ml; 95% CI: -3.14, -1.16; p < 0.001; GRADE = very low). Moreover, each 0.5 g/kg/day omega-3 fatty acids (parenteral) significantly reduced TNF-α (SMD: -1.11 pg/ml; 95% CI: -2.02, -0.19; p = 0.017; GRADE = low). With moderate and very low evidence certainty, each 1 g/day of omega-3 fatty acids supplementation (oral/enteral) has a beneficial effect on IL-6 and TNF-α. Each 0.5 g/kg/day omega-3 fatty acids (parenteral) could also exert a favorable impact on TNF-α, but the certainty of the evidence was low.

n-3 PUFAs Show Promise as Adjuvants in Chemotherapy, Enhancing their Efficacy while Safeguarding Hematopoiesis and Promoting Bone Generation.

Cancer ranks as the second leading cause of mortality in high-income countries, underscoring the critical need for effective therapeutic strategies. One prominent approach, chemotherapy, is widely employed for treating solid tumors. However, the significant adverse effects associated with chemotherapy, notably myeloablation and osteonecrosis, impart considerable challenges by compromising immune function and diminishing patients' quality of life. Furthermore, the emergence of chemotherapy resistance poses a formidable hurdle in achieving successful cancer treatment outcomes. In this context, the focus is on exploring alternative approaches to enhance the efficacy of cancer treatment and mitigate its adverse consequences. Among these approaches, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), two n-3 polyunsaturated fatty acids (PUFAs), have garnered substantial interest. These PUFAs exhibit the potential to influence membrane lipid composition and modulate critical gene expressions associated with cancer, such as Bcl-2, PI3K, NF-κB, and phosphorylated Akt, thereby potentially reducing cancer risk. Moreover, emerging evidence highlights their ability to augment chemotherapy efficacy, particularly in drug-resistant cancer cells. Importantly, both preclinical and clinical investigations have provided compelling evidence supporting the protective effects of n-3 PUFAs on healthy cells. Leveraging these findings, there has been growing attention on the exploration of n-3 PUFAs as adjuvants to chemotherapy. This strategic approach holds promise in mitigating the adverse effects linked to chemotherapy, notably myeloablation and osteonecrosis, while simultaneously enhancing its effectiveness in combating cancer. This comprehensive review delves into the multifaceted attributes of n-3 PUFAs, encompassing their cytotoxic properties, potential as chemopreventive agents, and their prospective role in ameliorating the adverse effects commonly associated with chemotherapy, with a particular emphasis on myeloablation and osteonecrosis. By elucidating the intricate interplay between n-3 PUFAs and cancer treatment paradigms, this review contributes to the expanding body of knowledge aimed at refining cancer therapeutic strategies and enhancing patient outcomes.

Fish oil minimises feed intake and improves insulin sensitivity in Zucker fa/fa rats.

Long-chain n-3 PUFA (LC n-3 PUFA) prevent, in rodents, insulin resistance (IR) induced by a high-fat and/or fructose diet but not IR induced by glucocorticoids. In humans, contrasting effects have also been reported. We investigated their effects on insulin sensitivity, feed intake (FI) and body weight gain in genetically insulin resistant male obese (fa/fa) Zucker (ZO) rats during the development of obesity. ZO rats were fed a diet supplemented with 7 % fish oil (FO) + 1 % corn oil (CO) (wt/wt) (ZOFO), while the control group was fed a diet containing 8 % fat from CO (wt/wt) (ZOCO). Male lean Zucker (ZL) rats fed either FO (ZLFO) or CO (ZLCO) diet were used as controls. FO was a marine-derived TAG oil containing EPA 90 mg/g + DHA 430 mg/g. During an oral glucose tolerance test, glucose tolerance remained unaltered by FO while insulin response was reduced in ZOFO only. Liver insulin sensitivity (euglycaemic-hyperinsulinaemic clamp + 2 deoxyglucose) was improved in ZOFO rats, linked to changes in phosphoenolpyruvate carboxykinase expression, activity and glucose-6-phosphatase activity. FI in response to intra-carotid insulin/glucose infusion was decreased similarly in ZOFO and ZOCO. Hypothalamic ceramides levels were lower in ZOFO than in ZOCO. Our study demonstrates that LC n-3 PUFA can minimise weight gain, possibly by alleviating hypothalamic lipotoxicity, and liver IR in genetically obese Zucker rats.

Neuroprotective and antioxidant effects of docosahexaenoic acid (DHA) in an experimental model of multiple sclerosis.

Multiple sclerosis (MS) is a chronic demyelinating disease, whose etiology is not yet fully understood, although there are several factors that can increase the chances of suffering from it. These factors include nutrition, which may be involved in the pathogenesis of the disease. In relation to nutrition, docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (n-3 PUFA), has emerged as an important player in the regulation of neuroinflammation, being considered a pleiotropic molecule. This study aimed to evaluate the effect of DHA supplementation on clinical state and oxidative stress produced by experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Twenty-five Dark Agouti rats which were used divided into Control Group, Control+Vehicle Group, Control+DHA Group, EAE Group, and EAE+DHA Group. DHA was administered for 51 days by intraperitoneal (i.p.) injection at a dose of 40 mg/kg, once a day, 5 days a week. DHA supplementation produced a decrease in oxidative stress, as well as an improvement in the clinical score of the disease. DHA could exert a beneficial effect on the clinic of MS, through the activation of the antioxidant factor Nrf2.

Fish oil-derived n-3 polyunsaturated fatty acids downregulate aquaporin 9 protein expression of liver and white adipose tissues in diabetic KK mice and 3T3-L1 adipocytes.

Aquaporin 9 (AQP9) is an integral membrane protein that facilitates glycerol transport in hepatocytes and adipocytes. Glycerol is necessary as a substrate for gluconeogenesis in the physiological fasted state, suggesting that inhibiting AQP9 function may be beneficial for treating type 2 diabetes associated with fasting hyperglycemia. The n-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are rich in fish oil and lower the risk of metabolic syndrome; however, the effects of EPA and DHA on AQP9 expression in obese and type 2 diabetes are unclear. The KK mouse is an animal model of obesity and type 2 diabetes because of the polymorphisms on leptin receptor gene, which results in a part of cause for obese and diabetic conditions. In this study, we determined the effect of fish oil-derived n-3 PUFA on AQP9 protein expression in the liver and white adipose tissue (WAT) of KK mice and mouse 3T3-L1 adipocytes. The expression of AQP9 protein in the liver, epididymal WAT, and inguinal WAT were markedly decreased following fish oil administration. We also demonstrated that n-3 PUFAs, such as DHA, and to a lesser extent EPA, downregulated AQP9 protein expression in 3T3-L1 adipocytes. Our results suggest that fish oil-derived n-3 PUFAs may regulate the protein expressions of AQP9 in glycerol metabolism-related organs in KK mice and 3T3-L1 adipocytes.

Effects of hydrolyzed collagen alone or in combination with fish oil on the gut microbiome in patients with major burns.

Burns are associated with gut dysbiosis. Collagen peptides and omega-3 fatty acids (FAs) are suggested to improve wound healing and the inflammatory response. These are also correlated with microbiome colonization. Therefore, the present study aimed to investigate the effect of hydrolyzed collagen alone or in combination with fish oil on specific species of the gut microbiome in patients with major burns. In this randomized double-blind clinical trial, 57 adults (aged 18-60 years) with 20-45% total body surface area burns were randomised into three groups to receive either 40 gr hydrolyzed collagen +10 ml sunflower oil, 40 g hydrolyzed collagen +10 ml fish oil or placebo, divided into two daily drinks, for two weeks. Gut bacteria were measured using the real-time quantitative polymerase chain reaction (qPCR) method. The mean concentration of Bifidobacterium was significantly reduced in the control (P = 0.002) and collagen (P = 0.005) groups compared with the baseline values, whereas no significant change was observed in the collagen omega-3 group. The Firmicutes to Bacteroidetes ratio decreased significantly in the collagen group (p = 0.002) after supplementation compared to baseline . No significant changes in concentration of Lactobacillus, Enterobacteriaceae, and F.prausnitzii were observed between or within the study groups. Two weeks of supplementation with collagen and omega-3 FAs in patients with major burns did not result in a significant difference in the concentration of bacteria measured between the study groups. However, the addition of omega-3 FAs prevented a significant reduction in gut Bifidobacterium. Future studies are suggested to investigate the potential efficacy of these nutrients in improving the gut microbiota and clinical outcomes in major burns. REGISTRATION NUMBER: IRCT20131125015536N9.