Dietary Polyunsaturated Fatty Acids Research Articles

Dietary fatty acids and mortality risk from heart disease in US adults: an analysis based on NHANES

We investigated the association of dietary intake of major types of fatty acids with heart disease mortality in a general adult cohort with or without a prior diagnosis of myocardial infarction (MI). This cohort study included US adults who attended the National Health and Nutrition Examination Surveys from 1988 to 2014. Heart disease mortality was ascertained by linkage to the National Death Index records through 31 December 2015. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of fatty acid intake for heart disease mortality. This cohort included 45,820 adults among which 1,541 had a prior diagnosis of MI. Participants were followed up for 532,722 person-years (mean follow-up, 11.6 years), with 2,313 deaths recorded from heart disease being recorded. Intake of saturated (SFAs) and monounsaturated fatty acids (MUFAs) was associated with heart disease mortality after adjustment for all the tested confounders. In contrast, a 5% higher calorie intake from polyunsaturated fatty acids (PUFAs) was associated with a 9% (HR, 0.91; 95% CI 0.83–1.00; P = 0.048) lower multivariate-adjusted risk of heart disease mortality. Sub-analyses showed that this inverse association was present in those without a prior diagnosis of MI (HR,0.89; 95% CI 0.80–0.99) but not in those with the condition (HR, 0.94; 95% CI 0.75–1.16). The lack of association in the MI group could be due to a small sample size or severity and procedural complications (e.g., stenting and medication adherence) of the disease. Higher PUFA intake was associated with a favourable lipid profile. However, further adjustment for plasma lipids did not materially change the inverse association between PUFAs and heart disease mortality. Higher intake of PUFAs, but not SFAs and MUFAs, was associated with a lower adjusted risk of heart disease mortality in a large population of US adults supporting the need to increase dietary PUFA intake in the general public.

The relationship of dietary antioxidant capacity with laboratory and anthropometric measurements in hemodialysis patients

Aim: Dietary antioxidant intake correlates with blood antioxidant content and protects against oxidative damage and related inflammatory complications. This study was conducted to examine the relationship between total antioxidant capacity of diet and effective factors with laboratory and anthropometric parameters in patients undergoing hemodialysis. Material and Method: The present case-control study consisted of 62 cases and 59 controls individuals who received hemodialysis treatment between the ages of 35-75. Dietary intake, sociodemographic data, medical history, and anthropometric measurements were collected from participants using a validated questionnaire. Results: Examining the association between dietary components and diet's total antioxidant capacity (dTAC) reveals a positive correlation between dietary protein (kg/avg), beta carotene (mcg/day), vitamin C (mg/day), vitamin E (mg/day), and polyunsaturated fatty acids (PUFA) (g/day) (p=0.002). The serum albumin, serum neutrophil to lymphocyte ratio and HDL-cholesterol have been reported to have a positive relationship with dTAC. And body mass ındex (BMI) and other anthropometric parameters were found to have a negative connection with dTAC (p=0.007). Conclusion: Total dietary antioxidant capacity is effective on anthropometric measurements and serum laboratory values. Increasing the antioxidant capacity of the diet in hemodialysis patients is important to prevent complications related to inflammation.

Interaction between SIDT2 and ABCA1 Variants with Nutrients on HDL-c Levels in Mexican Adults.

Previous studies have reported that the SIDT2 and ABCA1 genes are involved in lipid metabolism. We aimed to analyze the association-the gene x gene interaction between rs17120425 and rs1784042 on SIDT2 and rs9282541 on ABCA1 and their diet interaction on the HDL-c serum levels-in a cohort of 1982 Mexican adults from the Health Workers Cohort Study. Demographic and clinical data were collected through a structured questionnaire and standardized procedures. Genotyping was performed using a predesigned TaqMan assay. The associations and interactions of interest were estimated using linear and logistic regression. Carriers of the rs17120425-A and rs1784042-A alleles had slightly higher blood HDL-c levels compared to the non-carriers. In contrast, rs9282541-A was associated with low blood HDL-c levels (OR = 1.34, p = 0.013). The rs1784042 x rs9282541 interaction was associated with high blood HDL-c levels (p = 3.4 × 10-4). Premenopausal women who carried at least one rs17120425-A allele and consumed high dietary fat, protein, monounsaturated, or polyunsaturated fatty acids levels had higher HDL-c levels than the non-carriers. These results support the association between the genetic variants on SIDT2 and ABCA1 with HDL-c levels and suggest gene-gene and gene-diet interactions over HDL-c concentrations in Mexican adults. Our findings could be a platform for developing clinical and dietary strategies for improving the health of the Mexican population.

Increased Intake of Omega-3 Polyunsaturated Fatty Acids Is Associated with Reduced Odds of Low Hand Grip Strength in Korean Adults

Nutritional status is thought to be one of the modifiable risk factors for muscle health. This study investigates the association between dietary omega-3 polyunsaturated fatty acids (PUFA) intake and hand grip strength (HGS) in Korean adults. The cross-sectional analysis was performed on 18,278 participants aged ≥19 years enrolled in the Korea National Health and Nutrition Examination Survey from 2016-2019. Omega-3 PUFA consumption was positively linked to the dietary intake of nuts, fish, and shellfish in Korean adults. After adjusting for potential confounders, the results showed that increased omega-3 PUFA intake was associated with a decreased risk of low HGS (odds ratio (OR) for upper quartile (Q4) compared to Q1, men: OR = 1.42 (95% CI: 1.17-1.72), women: OR = 1.61 (1.37-1.89)). This inverse association was reported in people who did no resistance exercise or had an insufficient protein intake. In contrast, this association was not evident in adults who did resistance exercise or had sufficient protein intake. Furthermore, participants with hypertension or type 2 diabetes showed stronger associations between dietary omega-3 PUFA intake and HGS compared with other subgroups. These results suggest that dietary omega-3 PUFA intake positively related with HGS in Korean adults.

The Beneficial Effects of Pine Nuts and Its Major Fatty Acid, Pinolenic Acid, on Inflammation and Metabolic Perturbations in Inflammatory Disorders.

Inflammatory disorders such as atherosclerosis, diabetes and rheumatoid arthritis are regulated by cytokines and other inflammatory mediators. Current treatments for these conditions are associated with significant side effects and do not completely suppress inflammation. The benefits of diet, especially the role of specific components, are poorly understood. Polyunsaturated fatty acids (PUFAs) have several beneficial health effects. The majority of studies on PUFAs have been on omega-3 fatty acids. This review will focus on a less studied fatty acid, pinolenic acid (PNLA) from pine nuts, which typically constitutes up to 20% of its total fatty acids. PNLA is emerging as a dietary PUFA and a promising supplement in the prevention of inflammatory disorders or as an alternative therapy. Some studies have shown the health implications of pine nuts oil (PNO) and PNLA in weight reduction, lipid-lowering and anti-diabetic actions as well as in suppression of cell invasiveness and motility in cancer. However, few reviews have specifically focused on the biological and anti-inflammatory effects of PNLA. Furthermore, in recent bioinformatic studies on human samples, the expression of many mRNAs and microRNAs was regulated by PNLA indicating potential transcriptional and post-transcriptional regulation of inflammatory and metabolic processes. The aim of this review is to summarize, highlight, and evaluate research findings on PNO and PNLA in relation to potential anti-inflammatory benefits and beneficial metabolic changes. In this context, the focus of the review is on the potential actions of PNLA on inflammation along with modulation of lipid metabolism and oxidative stress based on data from both in vitro and in vivo experiments, and human findings, including gene expression analysis.

Preferential deposition of dairy derived fatty acids in muscle tissue is partially due to the upregulation of CD36 in a low-birth-weight swine model.

Metabolic syndrome is a worldwide health issue. Previous research has revealed that low-birth weight (LBW) swine fed a high-fat (HF) diet were susceptible to insulin resistance (IR) and developed a preferential intestinal lipid absorption, hypertriglyceridemia, and muscle steatosis. We hypothesized that fatty acid transporters such as CD36, FATP4, and FABP2 could potentially explain the development of these conditions. In addition, dairy-derived fatty acids have been shown to be valid biomarkers to assess dairy intake, which can be utilized to investigate muscle lipid deposition in LBW swine. The overall aim of this study was to delineate molecular transport candidates responsible for intestinal lipid absorption and muscle lipid deposition in LBW swine; and secondly to determine what dietary fatty acids might accumulate preferentially in pork muscle when consuming dairy products. At 5 weeks of age, normal birth weight (NBW) and LBW piglets were randomly assigned to three experimental diets: 1-chow diet, 2-HF diet, or 3-isocaloric HF diet supplemented with full fat dairy products. At 12 weeks of age, piglets were euthanized, and carcass, fasting plasma, biceps femoris and jejunum mucosal scrapings were collected. Results showed that HF-fed LBW swine exhibited early signs of IR (fasting glucose, P < 0.05; fasting insulin, P = 0.091; HOMA-IR, P = 0.086) compared with NBW-Chow, which were attenuated with increased dairy intake. Muscle samples from HF-fed LBW swine contained significantly more triglyceride compared to Chow-fed NBW swine (P < 0.05). Increased dairy intake significantly increased myristic acid (C14:0) and DPA (C22:5n3) relative to HF feeding alone (P < 0.05). All HF-fed LBW swine (regardless of dairy intake) exhibited an upregulation of CD36 expression (but not FABP2) compared with NBW littermates in both the small intestine and muscle (P < 0.05). Interestingly, increased dairy intake significantly increased the Canadian Lean Yield percentage in LBW swine fed an HF diet (P < 0.05). Findings from this study provide evidence on the mechanistic pathway of intestinal and muscle lipid metabolism in an innovative LBW swine model. We have also revealed that increasing dairy intake can enhance the incorporation of dietary long-chain polyunsaturated fatty acids into pork, as well as increasing the predicted lean yield of the carcass.

PS-BPP06-9: ASSOCIATIONS BETWEEN SERUM AND DIETARY OMEGA-3 FATTY ACID AND COGNITIVE FUNCTION IN A POPULATION OF COMMUNITY-DWELLING JAPANESE. TANUSHIMARU STUDY

Objective: Previous studies indicate that dietary omega-3 polyunsaturated fatty acids (PUFA) are modifiable risk factors for CVD and cognitive decline. This study aimed to investigate the association between serum and dietary omega-3 PUFA and cognitive function were measured in a general population. Design and method: A total of 976 residents (381 males, 595 females, mean age 62.6 years) underwent a physical examination, a nutrition survey and the mini-mental state examination as an evaluation of cognitive function in 2009 and followed up in 2018. Results: The serum omega-3/omega-6 ratio were significantly associated with age (p &lt; 0.0001), sex (male, p &lt; 0.0001), MMSE (p &lt; 0.0001), LDL-c (inversely, p &lt; 0.01), and salt intake (p &lt; 0.05), using by multiple stepwise regression analysis. The dietary intake of proteins from fish (p &lt; 0.0001), trace elements, (p &lt; 0.01), vitamin D, B6, B12 (p &lt; 0.0001), and salt (p &lt; 0.0001) showed dose dependent relationships with the serum omega-3/omega-6 ratio using analysis of covariance. Subjects were divided into 4 groups according to their progression of cognitive decline in 10 years. Serum omega-3 levels of group with normal cognitive function (NC) were significantly higher than those of group with cognitive decline (CD) (p &lt; 0.05). However, dietary intakes of omega-3 and omega-6 PUFA were not significant. Interestingly, salt intakes in group with CD were higher than those in group with NC (p &lt; 0.05). The logistic regression analysis revealed that salt intakes was associated with cognitive decline 10 years later after adjustments for confounding factors (odds ratio, 1.1; 95% C.I., 1.01–1.13; p = 0.01) Conclusion: The present study demonstrated that omega-3 PUFA may preserve a cognitive function and excessive intakes of salt may have an adverse effect on cognitive function.

Omega-3 polyunsaturated fatty acids and corneal nerve health: Current evidence and future directions.

Corneal nerves play a key role in maintaining ocular surface integrity. Corneal nerve damage, from local or systemic conditions, can lead to ocular discomfort, pain, and, if poorly managed, neurotrophic keratopathy. Omega-3 polyunsaturated fatty acids (PUFAs) are essential dietary components that play a key role in neural development, maintenance, and function. Their potential application in modulating ocular and systemic inflammation has been widely reported. Omega-3 PUFAs and their metabolites also have neuroprotective properties and can confer benefit in neurodegenerative disease. Several preclinical studies have shown that topical administration of omega-3 PUFA-derived lipid mediators promote corneal nerve recovery following corneal surgery. Dietary omega-3 PUFA supplementation can also reduce corneal epithelial nerve loss and promote corneal nerve regeneration in diabetes. Omega-3 PUFAs and their lipid mediators thus show promise as therapeutic approaches to modulate corneal nerve health in ocular and systemic disease. This review discusses the role of dietary omega-3 PUFAs in maintaining ocular surface health and summarizes the possible applications of omega-3 PUFAs in the management of ocular and systemic conditions that cause corneal nerve damage. In examining the current evidence, this review also highlights relatively underexplored applications of omega-3 PUFAs in conferring neuroprotection and addresses their therapeutic potential in mediating corneal nerve regeneration.

Association between dietary polyunsaturated fatty acids and their concentration in blood plasma, red blood cell, and semen of dogs.

In dogs, dietary omega 3 polyunsaturated fatty acids (n-3 PUFA) affect the fatty acid (FA) profile of blood plasma, erythrocyte membrane (EM), and semen, but their correlation has not yet been investigated. In this study, we evaluated the association between dietary PUFA and their profile in blood plasma, EM, and semen of dogs, with the possibility to predict the semen profile using the values of the three first. Twelve male dogs received the same standard commercial diet for 4 weeks. The FA profile was analyzed by gas chromatography in paired diet, blood (plasma and EM determinations), and semen samples. Data were analyzed with SAS Proc Corr version 9.4. Pearson´s correlation coefficient (significant if p < 0.05) was used to assess the association of dietary FA profiles with those in blood plasma, EM, and semen. There was a positive correlation between dietary eicosapentaenoic acid (EPA) and blood plasma (r = 0.97), EM (r = 0.94) and semen (r = 0.92) EPA, and between dietary docosahexaenoic acid (DHA) and arachidonic acid (ARA) and semen DHA (r = 0.93) and ARA (r = 0.92), respectively. There was a negative correlation between dihomo-gamma-linolenic acid (DGLA) in the diet and EM DGLA (r = -0.94). The dietary EPA is correlated with blood plasma, EM, and semen EPA concentrations, and dietary DHA and ARA are associated with semen DHA and ARA concentrations in dogs. These findings suggest that dietary EPA, DHA, and ARA concentrations could be helpful to predictive markers for such concentrations in the semen of dogs.

An evaluation of fatty acid profiles of two commercial diets on the growth of Indonesian shortfin eel,Anguilla bicolor

This study aimed to evaluate the effects of two commercial diets' fatty acid compositions on the growth and survival ofA. bicolor. Animal test weighing of 52.01±24.21 g were fed two different diets, such as : CEF (diet specially formulated for eels) and CFF (diet for freshwater fish). Myristic acid (4.16% and 4.32%), palmitic acid (22.45% and 33.97%), and stearic acid for the CFF diet (13.15%), comprised the majority of the diet's saturated fatty acids (SFAs). The monounsaturated fatty acids (MUFAs) were mainly palmitoleic acid (4.71% and 5.54%) and oleic acid (17.75% and 19.63%). Polyunsaturated fatty acids (PUFAs) were 37.5% and 14.1%, respectively. Essential fatty acids (EFAs), such as linoleic acid, alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid from the CEF diet were higher (3.73%, 1.25%, 9.22%, and 19.71%, respectively) than the CFF diet of 1.59%, 0.51%, 1.84%, and 7.99%, respectively. For eels fed the CEF and CFF diets, the ratio of n-3 to n-6 fatty acids was 4.14 and 0.66, respectively. Biomass production and fish survival were higher for the CEF diet animals. It can be concluded that the diet's PUFA and especially EFA contents further affect the growth and survival ofA. bicolor.

Effect of dietary omega-3 polyunsaturated fatty acids supplementation of Astyanax lacustris males on semen quality

Abstract This study aimed to verify whether the inclusion of omega-3 polyunsaturated fatty acids (PUFAs-ô3) in the diet of Astyanax lacustris males improves seminal quality. Four hundred fish were arranged in 20 boxes of 180 L in the recirculation system. These were fed with isoprotein diets (32% CP), until apparent satiation, with four levels of marine fish oil rich in PUFAs-ô3 inclusion (In% = 0, 3, 6, and 9), for 105 days. After, males were hormonally induced to spermiation, and semen was collected after 226 ATUs. Parameters evaluated were osmolality, seminal volume and color, spermatic concentration, sperm morphology, membrane integrity and, sperm motility (total and progressive motility, velocity curvilinear, straight line and average path, linearity and rectilinearity coefficients, trajectory oscillation, head lateral displacement amplitude, and cross-beat frequency). Seminal volume was greater in the In-0 and In-3 groups. Inclusion of PUFAs-ô3 positively influenced the kinetic parameters, as treatment with 6% and 9% of inclusion fish oil resulted in higher values for most of these parameters and did not differ statistically from each other. Thus, it is concluded that the addition of PUFAs-ô3 to the feed of breeders significantly improved the seminal quality of A. lacustris males.

Does Dietary Polyunsaturated Fatty Acid Intake Associate With Bone Mineral Density and Limb Structural Changes in Early Rheumatoid Arthritis?

Rheumatoid arthritis (RA) is an inflammatory disease that can result in bone erosion, lean mass lowering, and increase of fat mass without changes in body weight. The dietary consumption of polyunsaturated fatty acids (PUFAs) has been assessed in many studies due to their potential anti-inflammatory effect. The aim of this research was to identify if dietary intake of PUFAs associates with bone mineral density (BMD) and limb structural changes in early rheumatoid arthritis (ERA) compared to a population-based control group. The study was conducted because previous results have been insufficient. The study group consisted of 83 ERA patients and 321 control subjects. A dual-energy X-Ray absorptiometry (DXA) machine was used to measure hip, lumbar spine, and radius BMD, as well as arm and leg fat, lean, and bone mass. Dietary habits and inflammatory markers were assessed to evaluate the effects to BMD and limb structural changes. In ERA subjects, higher dietary consumption of PUFAs was associated with a decrease in arm fat mass (b -28.17, P = .02) and possibly with higher lumbar BMD (b 0.008, P = .058). Limb bone and lean mass changes were not associated with dietary intake of PUFAs. Balanced nutrition is essential. Consuming PUFAs could be beneficial in ERA preventing structural changes to hands, but additional research is needed.

Peroxisome proliferator-activated receptor pathways in diabetic rat decidua early after implantation: regulation by dietary polyunsaturated fatty acids

Research questionAre peroxisome proliferator-activated receptor (PPAR) pathways and moieties involved in histotrophic nutrition altered in the decidua of diabetic rats? Can diets enriched in polyunsaturated fatty acids (PUFA) administered early after implantation prevent these alterations? Can these dietary treatments improve morphological parameters in the fetus, decidua and placenta after placentation? DesignStreptozotocin-induced diabetic Albino Wistar rats were fed a standard diet or diets enriched in n3- or n6-PUFAs early after implantation. Decidual samples were collected on day 9 of pregnancy. Fetal, decidual and placental morphological parameters were evaluated on day 14 of pregnancy. ResultsOn gestational day 9, PPARδ levels showed no changes in the diabetic rat decidua compared with controls. In diabetic rat decidua, PPARα levels and the expression of its target genes Aco and Cpt1 had reduced. These alterations were prevented by the n6-PUFA-enriched diet. Levels of PPARγ, the expression of its target gene Fas, lipid droplet number and perilipin 2 and fatty acid binding protein 4 levels increased in the diabetic rat decidua compared with controls. Diets enriched with PUFA prevented PPARγ increase, but not the increased lipid-related PPARγ targets. On gestational day 14, fetal growth, decidual and placental weight reduced in the diabetic group, and alterations prevented by the maternal diets were enriched in PUFAs. ConclusionWhen diabetic rats are fed diets enriched in n3- and n6-PUFAs early after implantation, PPAR pathways, lipid-related genes and proteins, lipid droplets and glycogen content in the decidua are modulated. This influences decidual histotrophic function and later feto-placental development.

Effects of PUFA-Rich Dietary Strategies on Ruminants' Mammary Gland Gene Network: A Nutrigenomics Review.

Although the inclusion of polyunsaturated fatty acids (PUFAs) in ruminants' diets appears to be a well-documented strategy to enrich milk with PUFAs, several gene networks that regulate milk synthesis and mammary gland homeostasis could be impaired. The objective of this literature review is to assess the effects of nutritional strategies focused on enriching milk with PUFAs on gene networks regulating mammary gland function and lipogenesis, as well as the impact of feed additives and bioactive compounds with prominent antioxidant potential on immune-oxidative transcriptional profiling, as a part of mammary gland homeostasis and health. The findings support the conclusion that PUFAs' inclusion in ruminants' diets more strongly downregulate the stearoyl-CoA desaturase (SCD) gene compared to other key genes involved in de novo fatty acid synthesis in the mammary gland. Additionally, it was revealed that seed oils rich in linoleic and linolenic acids have no such strong impact on networks that regulate lipogenic homeostasis compared to marine oils rich in eicosapentaenoic and docosahexaenoic acids. Furthermore, ample evidence supports that cows and sheep are more prone to the suppression of lipogenesis pathways compared to goats under the impact of dietary marine PUFAs. On the other hand, the inclusion of feed additives and bioactive compounds with prominent antioxidant potential in ruminants' diets can strengthen mammary gland immune-oxidative status. Considering that PUFA's high propensity to oxidation can induce a cascade of pro-oxidant incidences, the simultaneous supplementation of antioxidant compounds and especially polyphenols may alleviate any side effects caused by PUFA overload in the mammary gland. In conclusion, future studies should deeply investigate the effects of PUFAs on mammary gland gene networks in an effort to holistically understand their impact on both milk fat depression syndrome and homeostatic disturbance.

Fatty Acids of Echinoderms: Diversity, Current Applications and Future Opportunities.

The phylum Echinodermata comprising the classes Asteroidea, Ophiuroidea, Echinoidea, Holothuroidea, and Crinodeia, is one of the important invertebrate groups. Members of this phylum live exclusively in marine habitats and are distributed in almost all depths and latitudes. Some of them, such as sea urchins and sea cucumbers, are commercially valuable and constitute a major fishery resource. Echinoderms are increasingly recognized as a unique source of various metabolites with a wide range of biological activities. The importance of dietary polyunsaturated fatty acids, such as eicosapentaenoic acid, in human health has drawn attention to echinoderms as a promising source of essential fatty acids (FAs). Extensive information on the FAs of the phylum has been accumulated to date. The biosynthetic capabilities and feeding habits of echinoderms explain the findings of the unusual FAs in them. Certain common and unusual FAs may serve as chemotaxonomic markers of the classes. The main goal of the review was to gather the relevant information on the distribution of FAs among the echinoderm classes, describe the structures, distribution, biosynthetic pathways, and bioactivity, with an emphasis on the FAs specific for echinoderms. A large part of the review is devoted to the FAs derived from echinoderms that exhibit various biological activities promising for potential therapeutic applications.

Low Sulfur Amino Acid, High Polyunsaturated Fatty Acid Diet Inhibits Breast Cancer Growth

Cancer cells may acquire resistance to stress signals and reprogram metabolism to meet the energetic demands to support their high proliferation rate and avoid death. Hence, targeting nutrient dependencies of cancer cells has been suggested as a promising anti-cancer strategy. We explored the possibility of killing breast cancer (BC) cells by modifying nutrient availability. We used in vitro models of BC (MCF7 and MDA-MB-231) that were maintained with a low amount of sulfur amino acids (SAAs) and a high amount of oxidizable polyunsatured fatty acids (PUFAs). Treatment with anti-apoptotic, anti-ferroptotic and antioxidant drugs were used to determine the modality of cell death. We reproduced these conditions in vivo by feeding BC-bearing mice with a diet poor in proteins and SAAs and rich in PUFAs (LSAA/HPUFA). Western blot analysis, qPCR and histological analyses were used to assess the anti-cancer effects and the molecular pathways involved. We found that BC cells underwent oxidative damage to DNA and proteins and both apoptosis and ferroptosis were induced. Along with caspases-mediated PARP1 cleavage, we found a lowering of the GSH-GPX4 system and an increase of lipid peroxides. A LSAA/HPUFA diet reduced tumor mass and its vascularization and immune cell infiltration, and induced apoptosis and ferroptotic hallmarks. Furthermore, mitochondrial mass was found to be increased, and the buffering of mitochondrial reactive oxygen species limited GPX4 reduction and DNA damage. Our results suggest that administration of custom diets, targeting the dependency of cancer cells on certain nutrients, can represent a promising complementary option for anti-cancer therapy.

Dietary supplementation of n-3 PUFAs ameliorates LL37-induced rosacea-like skin inflammation via inhibition of TLR2/MyD88/NF-κB pathway

Rosacea is a facial chronic inflammatory skin disease with dysfunction of immune and neurovascular system and treatments for rosacea are challenging. N-3 polyunsaturated fatty acids (PUFAs), one of essential fatty acids, are needed for health maintenance and exert anti-inflammation and immunomodulatory effects in a series of cutaneous diseases such as atopic dermatitis and photoaging through dietary supplementation. However, the role of n-3 PUFAs on rosacea remains to be elucidated. In this study, KEGG enrichment analysis and GO analysis indicated that the biological process and signaling pathways, including chemokine signaling pathway, regulated by n-3 PUFAs highly overlapped with those in the pathogenic biological process of rosacea, especially the erythema telangiectasia type. Next, mice were randomized to fed with a customized n-3 PUFAs diet. We showed that n-3 PUFAs ameliorated skin erythema, inhibited dermal inflammatory cell infiltration (mast cells, neutrophils, and CD4 +T cells) and suppressed elevated pro-inflammatory cytokines in LL37-induced rosacea-like mice. Besides, n-3 PUFAs were also verified to repress angiogenesis in LL37-induced mice skin. Further investigation revealed that n-3 PUFAs attenuated LL37-induced inflammation via TLR2/ MyD88/ NF-κB pathway both in mice and in keratinocytes. In conclusion, our findings underscore that dietary supplementation of n-3 PUFAs have the potential to become an efficient and safe clinical therapeutic candidate for rosacea.

Effects of altering the ratio of n-6 to n-3 fatty acids and concentrations of polyunsaturated fatty acids in diets on milk production and energy balance of Holstein cows

Our objective was to examine the effects of different ratios of n-6 to n-3 (n-6/n-3) fatty acids (FA) and amounts of PUFA on milk production and nutrient utiliza- tion in mid-lactating Holstein cows. Twenty-four lactating cows (550 ± 50 kg of BW and 100 ± 5 DIM) were randomly assigned to receive 1 of the 4 diets: (1) high n-6/n-3 (8.45) FA and low PUFA (19.0 g/kg of DM) concentration (n- 6-SFA), (2) high n-6/n-3 (8.78) FA and high PUFA (26.7 g/kg of DM) concentration (n-6-UFA), (3) low n-6/n-3 (5.74) FA and low PUFA (21.2 g/kg of DM) concentration (n-3-SFA), and (4) low n-6/n-3 (6.22) FA and high PUFA (26.7 g/kg of DM) concentration (n-3-UFA). The n-3-SFA diet improved milk production, fat- and energy-corrected milk, milk fat and protein yields, and digestibility of NDF compared with other diets. Dry matter intake, milk fat and protein content, BW, and BCS were not affected, although es- timated energy balance was lower in n-3-SFA compared with the other diets. The n-3-SFA diet had the greatest feed efficiency value. Partial replacement of SFA with n-3 FA (n-3-SFA) could be considered for improving produc- tion and feed efficiency in dairy cows. Decreasing the ra- tio of n-6/n-3 and the amount of dietary PUFA increased milk, milk-fat, and milk-protein yields, whereas DMI was similar; thus, feed conversion to milk improved. Therefore, diets containing similar concentrations of fat but greater n-3 FA and less content of PUFA may be beneficial for improving production in mid-lactating Holstein cows.

A ferroptosis-inducing biomimetic nanocomposite for the treatment of drug-resistant prostate cancer.

Second-generation androgen receptor (AR) inhibitors such as enzalutamide are the first-line treatments for castration-resistant prostate cancer (CRPC). Resistance to enzalutamide will greatly increase the difficulty of prostate cancer treatment and reduce the survival time of patients. However, drug-resistant cancer cells seem to be more sensitive to ferroptosis. Therefore, we constructed a biomimetic tumor-targeting magnetic lipid nanoparticle (t-ML) to codeliver dihomo-γ-linolenic acid (DGLA) and 2,4-dienoyl-CoA reductase 1 (DECR1) siRNA (t-ML@DGLA/siDECR1). DGLA is a dietary polyunsaturated fatty acid (PUFA), while DECR1 is overexpressed in prostate cancer and can inhibit the generation of PUFAs. The combination of DGLA and siDECR1 can efficiently induce ferroptosis by peroxidation of PUFAs, which has been verified both in vitro and in vivo. With the assistance of an external magnet, t-ML showed good tumor targeting ability and biocompatibility, and t-ML@DGLA/siDECR1 exhibited significant ferroptosis induction and tumor suppression capabilities. Moreover, in a nude mouse model of prostate cancer fed on a high-fat diet (HFD), there was no distant organ metastasis when the tumor-bearing mice were treated with t-ML@DGLA/siDECR1 and an external magnet, with upregulated PUFAs and downregulated monounsaturated fatty acids (MUFAs). Hence, this study has broadened the way of treating drug-resistant prostate cancer based on ferroptosis induction.

Interaction among dietary n-3 and n-6 polyunsaturated fatty acid intake, fatty acid desaturase 2 genetic variants, and low-density lipoprotein cholesterol levels in type 2 diabetes patients.

Fatty acid desaturase (FADS) genetic polymorphisms are strongly correlated with the risk of dyslipidemia and cardiovascular disease. In this study, we examined the impact of FADS1 and FADS2 genetic variants on plasma lipid status, and assessed interactions between FADS genetic polymorphisms and plasma n-3/n-6 fatty acids regarding lipid status within a population of 816 Taiwanese patients with type 2 diabetes. Selected tag single-nucleotide polymorphisms (FADS1 rs174546 [T/C]; FADS2 rs174602 [A/G] and rs2072114 [A/G]) were genotyped (n=816). The distribution of genotypes were compared with reports publicly available in the Genome Aggregation Database for East Asian populations (https://gnomad.broadinstitute.org). In the subgroup of patients not taking lipid-lowering medications (n=192), we observed that the G allele of FADS2 rs174602 was statistically significantly correlated with lower low-density lipoprotein cholesterol (LDL-C) concentrations (P=0.001), whereas the G allele of rs2072114 was marginally associated with LDL-C concentrations (P=0.091). Using a general linear model adjusted for confounding factors, statistically significant interactions (P= 0.016) between single-nucleotide polymorphisms in rs2072114 and a low alpha-linolenic acid (18:3n-3)/linoleic acid (18:2n-6) ratio; the G allele correlated with lower LDL-C levels among individuals with a low alpha-linolenic acid/linoleic acid ratio. Interaction between rs174602 single-nucleotide polymorphisms and low alpha-linolenic acid/linoleic acid values on LDL-C was only marginally significant (P= 0.063). Our results show the role of n-3/n-6 dietary polyunsaturated fatty acids in modifying the effects of genetic susceptibility on lipoprotein concentrations in patients with type 2 diabetes. Our findings highlight the potential of interventions with dietary polyunsaturated fatty acids regarding developing individualized prevention strategies for type 2 diabetes presenting with co-occurring dyslipidemia and cardiovascular diseases.