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 (n-3) Fatty Acid-Statin Interaction: Evidence for a Novel Therapeutic Strategy for Atherosclerotic Cardiovascular Disease.

Managing atherosclerotic cardiovascular disease (ASCVD) often involves a combination of lifestyle modifications and medications aiming to decrease the risk of cardiovascular outcomes, such as myocardial infarction and stroke. The aim of this article is to discuss possible omega-3 (n-3) fatty acid-statin interactions in the prevention and treatment of ASCVD and to provide evidence to consider for clinical practice, highlighting novel insights in this field. Statins and n-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) are commonly used to control cardiovascular risk factors in order to treat ASCVD. Statins are an important lipid-lowering therapy, primarily targeting low-density lipoprotein cholesterol (LDL-C) levels, while n-3 fatty acids address triglyceride (TG) concentrations. Both statins and n-3 fatty acids have pleiotropic actions which overlap, including improving endothelial function, modulation of inflammation, and stabilizing atherosclerotic plaques. Thus, both statins and n-3 fatty acids potentially mitigate the residual cardiovascular risk that remains beyond lipid lowering, such as persistent inflammation. EPA and DHA are both substrates for the synthesis of so-called specialized pro-resolving mediators (SPMs), a relatively recently recognized feature of their ability to combat inflammation. Interestingly, statins seem to have the ability to promote the production of some SPMs, suggesting a largely unrecognized interaction between statins and n-3 fatty acids with relevance to the control of inflammation. Although n-3 fatty acids are the major substrates for the production of SPMs, these signaling molecules may have additional therapeutic benefits beyond those provided by the precursor n-3 fatty acids themselves. In this article, we discuss the accumulating evidence that supports SPMs as a novel therapeutic tool and the possible statin-n-3 fatty acid interactions relevant to the prevention and treatment of ASCVD.

LDL receptor-related protein 5 selectively transports unesterified polyunsaturated fatty acids to intracellular compartments.

Polyunsaturated fatty acids (PUFAs), which cannot be synthesized by animals and must be supplied from the diet, have been strongly associated with human health. However, the mechanisms for their accretion remain poorly understood. Here, we show that LDL receptor-related protein 5 (LRP5), but not its homolog LRP6, selectively transports unesterified PUFAs into a number of cell types. The LDLa ligand-binding repeats of LRP5 directly bind to PUFAs and are required and sufficient for PUFA transport. In contrast to the known PUFA transporters Mfsd2a, CD36 and FATP2, LRP5 transports unesterified PUFAs via internalization to intracellular compartments including lysosomes, and n-3 PUFAs depend on this transport mechanism to inhibit mTORC1. This LRP5-mediated PUFA transport mechanism suppresses extracellular trap formation in neutrophils and protects mice from myocardial injury during ischemia-reperfusion. Thus, this study reveals a biologically important mechanism for unesterified PUFA transport to intracellular compartments.

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.

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.

Impacts of Omega-3 Fatty Acids, Natural Elixirs for Neuronal Health, on Brain Development and Functions.

Omega-3 fatty acids play a seminal role in maintaining the structural and functional integrity of the nervous system. These specialized molecules function as precursors for many lipid-based biological messengers. Also, studies suggest the role of these fatty acids in regulating healthy sleep cycles, cognitive ability, brain development, etc. Dietary intake of essential poly unsaturated fatty acids (PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are foundational to the optimal working of the nervous system. Besides regulating health, these biomolecules have great therapeutic value in treating several diseases, particularly nervous system diseases and disorders. Many recent studies conclusively demonstrated the beneficial effects of Omega-3 fatty acids in treating depression, neuropsychiatric disorders, neurodegenerative disorders, neurochemical disorders, and many other illnesses associated with the nervous system. This chapter summates the multifaceted role of poly unsaturated fatty acids, especially Omega-3 fatty acids (EPA and DHA), in the neuronal health and functioning. The importance of dietary intake of these essential fatty acids, their recommended dosages, bioavailability, the mechanism of their action, and therapeutic values are extensively discussed.

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.

Effects of niacin and omega-3 fatty acids on HDL-apolipoprotein A-I exchange in subjects with metabolic syndrome.

HDL-apolipoprotein A-I exchange (HAE) measures a functional property associated with HDL's ability to mediate reverse cholesterol transport. HAE has been used to examine HDL function in case-control studies but not in studies of therapeutics that alter HDL particle composition. This study investigates whether niacin and omega-3 fatty acids induce measurable changes in HAE using a cohort of fifty-six subjects with metabolic syndrome (MetS) who were previously recruited to a double-blind trial where they were randomized to 16 weeks of treatment with dual placebo, extended-release niacin (ERN, 2g/day), prescription omega-3 ethyl esters (P-OM3, 4g/day), or the combination. HAE was assessed at the beginning and end of the study. Compared to placebo, ERN and P-OM3 alone significantly increased HAE by 15.1% [8.2, 22.0] (P<0.0001) and 11.1% [4.5, 17.7] (P<0.0005), respectively, while in combination they increased HAE by 10.0% [2.5, 15.8] (P = 0.005). When HAE was evaluated per unit mass of apoA-I ERN increased apoA-I specific exchange activity by 20% (2, 41 CI, P = 0.02) and P-OM3 by 28% (9.6, 48 CI, P<0.0006). However the combination had no statistically significant effect, 10% (-9, 31 CI, P = 0.39). With regard to P-OM3 therapy in particular, the HAE assay detected an increase in this property in the absence of a concomitant rise in HDL-C and apoA-I levels, suggesting that the assay can detect functional changes in HDL that occur in the absence of traditional biomarkers.

Interaction between citalopram and omega-3 fatty acids on anxiety and depression behaviors and maintaining the stability of brain pyramidal neurons in mice.

This research was done to examine the combination of citalopram, an antidepressant drug, and omega-3 in a mice model of depression. Mice received citalopram (1 and 2 mg/kg) or omega-3 (10 and 20 mg/kg) daily over 30 days. Then, they were exposed to acute and chronic restraint stress to assess the possible increasing effect of omega-3 on the antidepressant and anxiolytic effects of citalopram. Elevated plus-maze (EPM) and forced swimming test (FST) were used to assess anxiety and depression symptoms in non-restraint stress (NRS), acute restraint stress (ARS), and chronic restraint stress (CRS) mice. The results indicated that induction of acute and chronic restraint stress reduced %OAT (Open arm time) and %OAE (Open arm entrance) in the EPM test but enhanced immobility time in the FST, showing anxiogenic- and depressive-like effects. These stresses reduced the stability of pyramidal neurons in the prefrontal cortex (PFC) and hippocampus. Aone and combination administration with citalopram and omega-3 induced anxiolytic- and antidepressant-like effects in NRS, ARS, and CRS mice. This combination usage increased the stability of pyramidal neurons in the PFC and hippocampus. These results suggested an interaction between citalopram and omega-3 upon the induction of anxiolytic- and antidepressant-like effects as well as augmentation of the ratio of pyramidal live to dark neurons in the PFC and hippocampus of the ARS and CRS mice.

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.

Combining proteins with n-3 PUFAs (EPA + DHA) and their inflammation pro-resolution mediators for preservation of skeletal muscle mass.

The optimal feeding strategy for critically ill patients is still debated, but feeding must be adapted to individual patient needs. Critically ill patients are at risk of muscle catabolism, leading to loss of muscle mass and its consequent clinical impacts. Timing of introduction of feeding and protein targets have been explored in recent trials. These suggest that "moderate" protein provision (maximum 1.2 g/kg/day) is best during the initial stages of illness. Unresolved inflammation may be a key factor in driving muscle catabolism. The omega-3 (n-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are substrates for synthesis of mediators termed specialized pro-resolving mediators or SPMs that actively resolve inflammation. There is evidence from other settings that high-dose oral EPA + DHA increases muscle protein synthesis, decreases muscle protein breakdown, and maintains muscle mass. SPMs may be responsible for some of these effects, especially upon muscle protein breakdown. Given these findings, provision of EPA and DHA as part of medical nutritional therapy in critically ill patients at risk of loss of muscle mass seems to be a strategy to prevent the persistence of inflammation and the related anabolic resistance and muscle loss.

N-3 polyunsaturated fatty acids attenuate amyloid-beta-induced toxicity in AD transgenic Caenorhabditis elegans via promotion of proteasomal activity and activation of PPAR-gamma.

Alzheimer's disease (AD) is a common neurodegenerative disease that causes progressive cognitive decline. A major pathological characteristic of AD brain is the presence of senile plaques composed of ß-amyloid (Aß), the accumulation of which induces toxic cascades leading to synaptic dysfunction, neuronal apoptosis, and eventually cognitive decline. Dietary n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for patients with early-stage AD; however, the mechanisms are not completely understood. In this study, we investigated the effects of n-3 PUFAs on Aß-induced toxicity in a transgenic AD Caenorhabditis elegans (C. elegans) model. The results showed that EPA and DHA significantly inhibited Aß-induced paralytic phenotype and decreased the production of reactive oxygen species while reducing the levels of Aß in the AD worms. Further studies revealed that EPA and DHA might reduce the accumulation of Aß by restoring the activity of proteasome. Moreover, treating worms with peroxisome proliferator-activated receptor (PPAR)-γ inhibitor GW9662 prevented the inhibitory effects of n-3 PUFAs on Aß-induced paralytic phenotype and diminished the elevation of proteasomal activity by n-3 PUFAs, suggesting that PPARγ-mediated signals play important role in the protective effects of n-3 PUFAs against Aß-induced toxicity.

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.

The efficacy of Omega-3 polyunsaturated fatty acids for severe burn patients: A systematic review and trial sequential meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: Severe burns lead to metabolic changes, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Omege-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties. In the absence of substantial evidence for use on major burns, we systematically reviewed the efficacy of omega-3 PUFAs for patients with severe burns. METHODS: We comprehensively searched MEDLINE, Web of Science, Embase, Cochrane Library, China National Knowledge Internet, Wang Fang Data, Chinese Biomedicine Database, and Science Direct databases to collect randomised controlled trials of omega-3 PUFAs administered to patients with burns from January 2000 to June 2023. Two researchers independently screened the literatures, extracted the data, and assessed the risk of bias in the included studies. The outcomes were mortality, the risk of severe sepsis, septic shock, and multiple organ dysfunction syndrome. Data synthesis was conducted using Review Manager. Trial sequential analyses (TSA) for outcomes were performed. RESULTS: Three randomised controlled trials involving 140 patients were included. Of these, 71 patients received omega-3 PUFAs. The results showed that omega-3 PUFAs significantly reduced the incidence of severe sepsis, septic shock, multiple organ dysfunction syndrome (RR = 0.38, 95 % CI [0.19, 0.75], P = 0.005), C-reactive protein levels (MD = -39.70[-81.63, 2.23], P = 0.06), and improved respiratory outcomes. However, there was no difference in 14-day mortality (RR = 1.10, 95%CI [0.59, 2.05], P = 0.75). TSA showed that the results for the incidence of severe sepsis, septic shock, multiple organ dysfunction syndrome are insufficient and inconclusive. CONCLUSIONS: Omega-3 PUFAs may reduce inflammatory response and risk of sepsis, septic shock, and multiple organ dysfunction syndrome in severe burns patients and may shorten hospital stay but cannot reduce risk of death. Due to the limitation of the quantity and quality of the included studies, the evidence level is low, and the conclusions need to be verified by larger scale and higher quality randomised controlled trials.

The adjuvant treatment role of ω-3 fatty acids by regulating gut microbiota positively in the acne vulgaris.

Objectives:We aimed to explore the potential role of omega-3 (ω-3) fatty acids on acne vulgaris by modulating gut microbiota.Materials and Methods:We randomly divided the untreated acne patients into two groups with or without ω-3 fatty acids intervention for 12 weeks. The Sprague Dawley (SD) rats with acne model were given isotretinoin, ω-3 fatty acids or their combination respectively. Then the colonic contents samples of the drug intervention SD rats were transferred to the pseudo sterile rats with acne model. The severity of the disease was assessed by the Global Acne Grading System (GAGS) score of the patients, and the swelling rate of auricle and the pathological section of the rat with acne model. The 16S rDNA gene sequencing was performed to detect the alteration of the gut microbiota.Results:ω-3 fatty acids could increase the diversity of the gut microbiota and regulate the flora structure positively both in the patients and rats, increase the abundance of butyric acid producing bacteria and GAGS score in the patients, and alleviate the inflammation and comedones of rats.Conclusion:Supplementation of ω-3 fatty acids could alleviate the inflammation of acne vulgaris by increasing the abundance of butyric acid producing bacteria.

Effects of n-3 polyunsaturated fatty acid supplementation on appetite: a systematic review and meta-analysis of controlled clinical trials.

BACKGROUND: The current studies explore the effect of omega-3 polyunsaturated fatty acids (PUFAs) on appetite. OBJECTIVE: To examine the effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on appetite using a systematic review and meta-analysis of controlled clinical trials (CTs). PATIENTS AND METHODS: Online databases including PubMed, Scopus, ISI Web of Science, and Google Scholar were searched up to January 2022. A random-effects model was used to compare the overall standardized mean difference in appetite scores between n-3 PUFAs supplemented and control individuals. RESULTS: Fifteen eligible CTs with 1504 participants (872 for n-3 PUFA supplementation and 632 for placebo groups) were included in our systematic review. The meta-analysis showed no significant difference in overall appetite score between n-3 PUFAs supplemented and control groups (standardized mean difference [SMD] = 0.458, 95% confidence interval [CI] - 0.327, 1.242, P value = 0.25). However, the n-3 PUFA supplementation significantly increased the desire to eat (SMD = 1.07, 95% CI 0.116, 2.029, P = 0.02) compared to control. CONCLUSION: Although we found no effect of omega-3 supplementation on overall appetite score, it modestly increases the desire to eat. Further CTs evaluating the effect of PUFAs on appetite are still needed to confirm these findings.

Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use.

Dietary polyunsaturated fatty acids (PUFA) are increasingly recognized for their health benefits, whereas a high production of endogenous fatty acids - a process called de novo lipogenesis (DNL) - is closely linked to metabolic diseases. Determinants of PUFA incorporation into complex lipids are insufficiently understood and may influence the onset and progression of metabolic diseases. Here we show that fatty acid synthase (FASN), the key enzyme of DNL, critically determines the use of dietary PUFA in mice and humans. Moreover, the combination of FASN inhibition and PUFA-supplementation decreases liver triacylglycerols (TAG) in mice fed with high-fat diet. Mechanistically, FASN inhibition causes higher PUFA uptake via the lysophosphatidylcholine transporter MFSD2A, and a diacylglycerol O-acyltransferase 2 (DGAT2)-dependent incorporation of PUFA into TAG. Overall, the outcome of PUFA supplementation may depend on the degree of endogenous DNL and combining PUFA supplementation and FASN inhibition might be a promising approach to target metabolic disease.

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.