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Biomarkers based on DNA methylation are relevant in the field of environmental health for precision health. Although tobacco smoking is one of the factors with a strong and consistent impact on DNA methylation, there are very few studies analyzing its methylation signature in southern European populations and none examining its modulation by the Mediterranean diet at the epigenome-wide level. We examined blood methylation smoking signatures on the EPIC 850 K array in this population (n = 414 high cardiovascular risk subjects). Epigenome-wide methylation studies (EWASs) were performed analyzing differential methylation CpG sites by smoking status (never, former, and current smokers) and the modulation by adherence to a Mediterranean diet score was explored. Gene-set enrichment analysis was performed for biological and functional interpretation. The predictive value of the top differentially methylated CpGs was analyzed using receiver operative curves. We characterized the DNA methylation signature of smoking in this Mediterranean population by identifying 46 differentially methylated CpGs at the EWAS level in the whole population. The strongest association was observed at the cg21566642 (p = 2.2 × 10−32) in the 2q37.1 region. We also detected other CpGs that have been consistently reported in prior research and discovered some novel differentially methylated CpG sites in subgroup analyses. In addition, we found distinct methylation profiles based on the adherence to the Mediterranean diet. Particularly, we obtained a significant interaction between smoking and diet modulating the cg5575921 methylation in the AHRR gene. In conclusion, we have characterized biomarkers of the methylation signature of tobacco smoking in this population, and suggest that the Mediterranean diet can increase methylation of certain hypomethylated sites.

Purpose of review Nonalcoholic fatty liver is the result of an imbalance between lipid storage [from meal, de novo lipogenesis (DNL) and fatty acid (FA) uptake] and disposal (oxidation and VLDL output). Knowledge on the contribution of each of these pathways to liver fat content in humans is essential to develop tailored strategies to prevent and treat nonalcoholic fatty liver. Here, we review the techniques available to study the different storage pathways and review dietary modulation of these pathways. Recent findings The type of carbohydrate and fat could be of importance in modulating DNL, as complex carbohydrates and omega-3 FAs have been shown to reduce DNL. No effects were found on the other pathways, however studies investigating this are scarce. Techniques used to assess storage pathways are predominantly stable isotope techniques, which require specific expertise and are costly. Validated biomarkers are often lacking. These methodological limitations also translate into a limited number of studies investigating to what extent storage pathways can be modulated by diet. Further research is needed to elucidate in more detail the impact that fat and carbohydrate type can have on liver fat storage pathways and content.

Age‐associated diseases are rising to pandemic proportions, exposing the need for efficient and low‐cost methods to tackle these maladies at symptomatic, behavioral, metabolic, and physiological levels. While nutrition and health are closely intertwined, our limited understanding of how diet precisely influences disease often precludes the medical use of specific dietary interventions. Caloric restriction (CR) has approached clinical application as a powerful, yet simple, dietary modulation that extends both life‐ and healthspan in model organisms and ameliorates various diseases. However, due to psychological and social‐behavioral limitations, CR may be challenging to implement into real life. Thus, CR‐mimicking interventions have been developed, including intermittent fasting, time‐restricted eating, and macronutrient modulation. Nonetheless, possible side effects of CR and alternatives thereof must be carefully considered. We summarize key concepts and differences in these dietary interventions in humans, discuss their molecular effects, and shed light on advantages and disadvantages., Can dietary modulations promote better health? The current article comprehensively reviews key concepts of dietary interventions, their clinical application and the beneficial and disadvantageous effects of caloric restriction and fasting on human health.

Mammalian mitochondria contain small genomes [mitochondrial DNA (mtDNA)], which encode several of the proteins that are crucial for respiration. As such, maintaining the integrity of mtDNA is essential for healthy life. Nutritional strategies such as “Calorie Restriction” may play an important role in regulating mtDNA integrity and prolonging lifespan. In this review, we compare mtDNA with nuclear DNA damage and discuss how the resulting cell fates relate to human health. We provide a description of the mechanisms behind Calorie Restriction as an approach to induce mitochondrial processes contributing to a longer lifespan. We make connections between the current repertoire of studies to propose that how nutrition may mitigate mitochondrial dysfunction and potentially reduce DNA damage. Finally, we describe nutritional-based approaches to prevent mitochondrial dysfunction with a focus on mimetics of dietary and calorie restriction.

Edible insects are proposed as a nutritious and environmentally sustainable alternative source to animal proteins, due to their numerous advantages in terms of reduced ecological impact and high nutritional value. However, the novelty for edible insects relies on the content of bioactive ingredients potentially able to induce a functional effect in the body. The present review summarizes the main findings on the antioxidant properties of edible insects available in the literature. A total of 30 studies involving animals, cell cultures, or in vitro experimental studies evaluating the antioxidant effect of edible insects are presented in this work. When the antioxidant activity was investigated, using a wide variety of in vitro tests and in cellular models, positive results were shown. Dietary supplementation with edible insects was also able to counteract dietary oxidative stress in animal models, restoring the balance of antioxidant enzymes and reducing the formation of oxidation damage markers. On the basis of the reviewed evidences, edible insects might represent a source of novel redox ingredients at low ecological impact able to modulate oxidative stress. However, due to the fact that majority of these evidences have been obtained in vitro and in cellular and animal models, dietary intervention trials are needed to assess the efficacy of edible insect consumption to modulate redox status in humans.

Personalised dietary modulation of the gut microbiota may be key to disease management. Current investigations provide a broad understanding of the impact of diet on the composition and activity of the gut microbiota, yet detailed knowledge in applying diet as an actionable tool remains limited. Further to the relative novelty of the field, approaches are yet to be standardised and extremely heterogeneous research outcomes have ensued. This may be related to confounders associated with complexities in capturing an accurate representation of both diet and the gut microbiota. This review discusses the intricacies and current methodologies of diet-microbial relations, the implications and limitations of these investigative approaches, and future considerations that may assist in accelerating applications. New investigations should consider improved collection of dietary data, further characterisation of mechanistic interactions, and an increased focus on -omic technologies such as metabolomics to describe the bacterial and metabolic activity of food degradation, together with its crosstalk with the host. Furthermore, clinical evidence with health outcomes is required before therapeutic dietary strategies for microbial amelioration can be made. The potential to reach detailed understanding of diet-microbiota relations may depend on re-evaluation, progression, and unification of research methodologies, which consider the complexities of these interactions.

A dramatic rise in the prevalence of nonalcoholic fatty liver (NAFL) has been observed over the last few decades and it is now considered to be the most common liver disorder worldwide [1]. NAFL is characterized by excessive fat accumulation in the liver that is not associated with high alcohol consumption and NAFL can progress to more severe stages of liver disease. Importantly, even if no further progression of liver disease occurs, NAFL per se is also very strongly associated with metabolic diseases such as cardiovascular disease and type II diabetes [2–4]. Excessive fat accumulation in the liver is thought to be the result of an imbalance between lipid storage (due to increased delivery and synthesis), and disposal (Fig. ​(Fig.1).1). It is now well established that fat that is stored in the liver (in hepatocytes) originates from three main sources: first, direct fat storage from a meal; second, de novo synthesis of fatty acids (FAs) from glucose, fructose or amino acids (de novo lipogenesis; DNL); third, from uptake of plasma non-esterified FAs (NEFA) mainly derived from adipose tissue lipolysis (Fig. ​(Fig.1).1). Knowledge on the contribution of each of these pathways to liver fat content in humans is sparse [5,6], in part because appropriate techniques are lacking. Gaining a better understanding of the mechanisms, which contribute to hepatic fat accumulation is crucial to the development of effective treatment strategies for NAFL and its associated metabolic disturbances. Here, we discuss the techniques available to study storage pathways contributing to NAFL and review recent nutritional studies using these techniques to investigate whether these pathways can be modulated by diet. Open in a separate window FIGURE 1 Overview of liver fat storage and disposal pathways. Storage pathways include direct fat storage from a meal, de novo lipogenesis from carbohydrates and adipose tissue derived non-esterified fatty acid uptake. Liver lipid disposal pathways are mitochondrial fatty acid oxidation and ketogenesis after initial s-oxidation (acetyl-CoA disposal), and triglyceride incorporation into VLDL-particles to be secreted into the circulation.

This study explored the effects of natural growth promoters (phytogenic feed additives and organic acids) on animal performance, carcass characteristics, blood parameters, gut microflora composition, and microbe–host interactions in broiler chickens over a 42-day feeding period. Two-hundred-fifty-day-old chicks were randomly assigned to one of five treatments: (i) control diets (CON); (ii) control diets + 40 g/tons antibiotic growth promoter (AB); (iii) control diets + 3 kg/tons organic acids (ORG); (iv) control diets + 3 kg/tons phytogenic feed additives (PHY); (v) control diets + 3 kg/tons organic acids + phytogenic feed additive combination (COM). A non-significant differences (p > 0.05) were observed in broiler performance among treatments at 21 days of age; however, a gradually increasing body weight gain and reduced feed conversion ratio were observed at 42 days in treatments versus control group. Biochemical indices were non-significant (p > 0.05) except for decreased cholesterol (p

Epigenetics is the study of heritable mechanisms that can modify gene activity and phenotype without modifying the genetic code. The basis for the concept of epigenetics originated more than 2,000 yr ago as a theory to explain organismal development. However, the definition of epigenetics continues to evolve as we identify more of the components that make up the epigenome and dissect the complex manner by which they regulate and are regulated by cellular functions. A substantial and growing body of research shows that nutrition plays a significant role in regulating the epigenome. Here, we critically assess this diverse body of evidence elucidating the role of nutrition in modulating the epigenome and summarize the impact such changes have on molecular and physiological outcomes with regards to human health.

Emerging evidence and an in-depth understanding of the microbiome have helped in identifying beneficial commensals and their therapeutic potentials. Specific commensal taxa/ strains of the human gut microbiome have been positively associated with human health and recently termed as next-generation probiotics (NGPs). Of these, Akkermansia muciniphila, Ruminococcus bromii, Faecalibacterium prausnitzii, Anaerobutyricum hallii, and Roseburia intestinalis are the five most relevant gut-derived NGPs that have demonstrated therapeutic potential in managing metabolic diseases. Specific and natural dietary interventions can modulate the abundance and activity of these beneficial bacteria in the gut. Hence, the understanding of targeted stimulation of specific NGP by specific probiotic-targeted diets (PTD) is indispensable for the rational application of their combination. The supplementation of NGP with its specific PTD will help the strain(s) to compete with harmful microbes and acquire its niche. This combination would enhance the effectiveness of NGPs to be used as “live biotherapeutic products” or food nutraceuticals. Under the current milieu, we review various PTDs that influence the abundance of specific potential NGPs, and contemplates potential interactions between diet, microbes, and their effects on host health. Taking into account the study mentioned, we propose that combining NGPs will provide an alternate solution for developing the new diet in conjunction with PTD.

Trace elements (TEs) are essential for diverse processes maintaining body function and health status. The complex regulation of the TE homeostasis depends among others on age, sex, and nutritional status. If the TE homeostasis is disturbed, negative health consequences can result, e.g., caused by impaired redox homeostasis and genome stability maintenance. Based on age-related shifts in TEs which have been described in mice well-supplied with TEs, we aimed to understand effects of a long-term feeding with adequate or suboptimal amounts of four TEs in parallel. As an additional intervention, we studied mice which received an age-adapted diet with higher concentrations of selenium and zinc to counteract the age-related decline of both TEs. We conducted comprehensive analysis of diverse endpoints indicative for the TE and redox status, complemented by analysis of DNA (hydroxy)methylation and markers denoting genomic stability maintenance. TE concentrations showed age-specific alterations which were relatively stable and independent of their nutritional supply. In addition, hepatic DNA hydroxymethylation was significantly increased in the elderly mice and markers indicative for the redox status were modulated. The reduced nutritional supply with TEs inconsistently affected their status, with most severe effects regarding Fe deficiency. This may have contributed to the sex-specific differences observed in the alterations related to the redox status and DNA repair activity. Overall, our results highlight the complexity of factors impacting on the TE status and its physiological consequences. Alterations in TE supply, age, and sex proved to be important determinants that need to be taken into account when considering TE interventions for improving general health and supporting convalescence in the clinics., Graphical abstract Image 1, Highlights • Trace element profiles differ by age and sex under moderately modulated TE supply. • Maintenance of age-related trace element shifts through all feeding groups. • Cu/Zn ratio and DNA hydroxymethylation emerge as appropriate murine ageing markers.

Background Diet-derived short-chain fatty acids (SCFAs) in the rumen have broad effects on the health and growth of ruminants. The microbe-G-protein-coupled receptor (GPR) and microbe-histone deacetylase (HDAC) axes might be the major pathway mediating these effects. Here, an integrated approach of transcriptome sequencing and 16S rRNA gene sequencing was applied to investigate the synergetic responses of rumen epithelium and rumen microbiota to the increased intake of dietary non-fiber carbohydrate (NFC) from 15 to 30% in the goat model. In addition to the analysis of the microbial composition and identification of the genes and signaling pathways related to the differentially expressed GPRs and HDACs, the combined data including the expression of HDACs and GPRs, the relative abundance of the bacteria, and the molar proportions of the individual SCFAs were used to identify the significant co-variation of the SCFAs, clades, and transcripts. Results The major bacterial clades promoted by the 30% NFC diet were related to lactate metabolism and cellulose degradation in the rumen. The predominant functions of the GPR and HDAC regulation network, under the 30% NFC diet, were related to the maintenance of epithelium integrity and the promotion of animal growth. In addition, the molar proportion of butyrate was inversely correlated with the expression of HDAC1, and the relative abundance of the bacteria belonging to Clostridum_IV was positively correlated with the expression of GPR1. Conclusions This study revealed that the effects of rumen microbiota-derived SCFA on epithelium growth and metabolism were mediated by the GPR and HDAC regulation network. An understanding of these mechanisms and their relationships to dietary components provides better insights into the modulation of ruminal fermentation and metabolism in the promotion of livestock production. Electronic supplementary material The online version of this article (10.1186/s40168-017-0341-z) contains supplementary material, which is available to authorized users.

Received: 2017-01-09 | Accepted: 2017-02-24 | Available online: 2017-06-20 http://dx.doi.org/10.15414/afz.2017.20.01.31-35 Ageing is accompanied by physiological changes in the human oral cavity. These include potential reduction of the fungiform papillae (FP) density which has been associated with impaired taste acuity. Because the studies have demonstrated either contrary or non-significant evidences, we decided to verify the hypothesis about FP reduction and ageing. Total of 150 human living subjects aged 19–87 years participated in the study. The tongues were stained with blue food dye, quantification area with 10 mm diameter was defined, and images of the tongues were captured with digital camera. The number of FP has been scored on each photo by five individual scorers according to a decision tree. The scoring was accomplished in ImageJ open source program using a cell counter plugin. The mean FP density value within all subjects was 18.02 ±15.95 FP per cm -2 , the lowest and the highest values were 0.25 ±0.57 FP per cm -2 and 65.00 ±1.66 FP per cm -2 of the tongue tip, respectively. Based on age, the subjects were divided into categories with 6.0 increasing step, in order access effect of ageing on FP densities. Age categories were significantly different in mean FP densities as determined by Welch's F (8, 22.04) = 28.81, P

The concept that dietary changes could improve the response to cancer therapy is extremely attractive to many patients, who are highly motivated to take control of at least some aspect of their treatment. Growing insight into cancer metabolism is highlighting the importance of nutrient supply to tumor development and therapeutic response. Cancers show diverse metabolic requirements, influenced by factors such as tissue of origin, microenvironment, and genetics. Dietary modulation will therefore need to be matched to the specific characteristics of both cancers and treatment, a precision approach requiring a detailed understanding of the mechanisms that determine the metabolic vulnerabilities of each cancer.

The concept of using specific dietary components to selectively modulate the gut microbiota to confer a health benefit, defined as prebiotics, originated in 1995. In 2018, a group of scientists met at the International Scientific Association for Probiotics and Prebiotics annual meeting in Singapore to discuss advances in the prebiotic field, focussing on issues affecting functionality, research methodology, and geographical differences. The discussion ranged from examining scientific literature supporting the efficacy of established prebiotics, to the prospects for establishing health benefits associated with novel compounds, isolated from different sources. While many promising candidate prebiotics from across the globe have been highlighted in preliminary research, there are a limited number with both demonstrated mechanism of action and defined health benefits as required to meet the prebiotic definition. Prebiotics are part of a food industry with increasing market sales, yet there are great disparities in regulations in different countries. Identification and commercialisation of new prebiotics with unique health benefits means that regulation must improve and remain up-to-date so as not to risk stifling research with potential health benefits for humans and other animals. This summary of the workshop discussions indicates potential avenues for expanding the range of prebiotic substrates, delivery methods to enhance health benefits for the end consumer, and guidance to better elucidate their activities in human studies. This article is protected by copyright. All rights reserved.

Western lifestyle is linked to autoimmune and metabolic diseases, driven by changes in diet and gut microbiota composition. Using a Toll-like receptor 7 (TLR7)-dependent mouse models of lupus, we dissect dietary effects on the gut microbiota and find that Lactobacillus reuteri can drive autoimmunity but is ameliorated via dietary resistant starch (RS). Culture of internal organs and 16S rDNA sequencing revealed TLR7-dependent translocation of Lactobacillus reuteri in mice and fecal enrichment of Lactobacillus in a subset of lupus patients. L. reuteri colonization worsened autoimmune manifestations under specific-pathogen-free and gnotobiotic conditions, notably increasing plasmacytoid dendritic cells (pDCs) and interferon signaling. However, RS suppressed the abundance and translocation of L. reuteri via short-chain fatty acids, which inhibited its growth. Additionally, RS decreased pDCs, interferon pathways, organ involvement and mortality. Thus, RS exerts beneficial effects in lupus-prone hosts through suppressing a pathobiont that mediates interferon pathways implicated in the pathogenesis of human autoimmunity.

Utilization of marine algae has increased considerably over the past decades, since biodiversity within brown, red and green marine algae offers possibilities of finding a variety of bioactive compounds. Marine algae are rich sources of dietary fibre. The remarkable positive effects of seaweed dietary fibre on human body are related to their prebiotic activity over the gastrointestinal tract (GIT) microbiota. However, dietary modulation of microorganisms present in GIT can be influenced by different factors such as type and source of the dietary fibre, their molecular weight, type of extraction and purification methods employed, composition and modification of polysaccharide and oligosaccharide. This review will demonstrate evidence that polysaccharides and oligosaccharides from marine algae can be used as prebiotics, emphasizing their use in human health, their application as food and other possible applications. Furthermore, an important approach of microbial enzymes employment during extraction, modification or production of those prebiotics is highlighted.

Simple Summary Throughout the world, piglet mortality and morbidity in large litters are a major welfare concern and source of economic losses. Gastro-intestinal problems rank amongst the highest causes of morbidity, mortality and antimicrobial use. As evidenced in the recent literature, nutritional interventions before and after weaning can modulate gut development, thereby reducing the risk of gastro-intestinal problems. In particular, early-life nutrition has begun to receive increasing interest, given its potential to modulate gut health in the long-term. The literature nevertheless contains little information on how pre-weaning and post-weaning nutritional strategies can be combined to sustain optimal gut health throughout the challenging process of weaning. To address this gap in current knowledge, this review summarises a large body of literature on nutritional strategies aimed at supporting gut health in piglets, combining individual strategies into a structured nutritional approach over time, starting from a few days after birth to 5–6 weeks post-weaning. The review also contains propositions concerning potential avenues for future research that may contribute to the reduction in gastro-intestinal problems and the associated use of antimicrobials in the pig industry. Abstract This is a comprehensive review on the use of nutritional strategies to shape the functioning of the gastro-intestinal tract in suckling and weaned piglets. The progressive development of a piglet’s gut and the associated microbiota and immune system offers a unique window of opportunity for supporting gut health through dietary modulation. This is particularly relevant for large litters, for which sow colostrum and milk are insufficient. The authors have therefore proposed the use of supplemental milk and creep feed with a dual purpose. In addition to providing nutrients to piglets, supplemental milk can also serve as a gut modulator in early life by incorporating functional ingredients with potential long-term benefits. To prepare piglets for weaning, it is important to stimulate the intake of solid feed before weaning, in addition to stimulating the number of piglets eating. The use of functional ingredients in creep feed and a transition diet around the time of weaning helps to habituate piglets to solid feed in general, while also preparing the gut for the digestion and fermentation of specific ingredients. In the first days after weaning (i.e., the acute phase), it is important to maintain high levels of feed intake and focus on nutritional strategies that support good gastric (barrier) function and that avoid overloading the impaired digestion and fermentation capacity of the piglets. In the subsequent maturation phase, the ratio of lysine to energy can be increased gradually in order to stimulate piglet growth. This is because the digestive and fermentation capacity of the piglets is more mature at this stage, thus allowing the inclusion of more fermentable fibres. Taken together, the nutritional strategies addressed in this review provide a structured approach to preparing piglets for success during weaning and the period that follows. The implementation of this approach and the insights to be developed through future research can help to achieve some of the most important goals in pig production: reducing piglet mortality, morbidity and antimicrobial use.

Colorectal cancer is a major global cause of morbidity and mortality. Current strategies employed to increase detection of early, curable stages of this disease are contributing to a reduction of the negative health impact from it. While there is a genetic component to the risk of disease, diet and environment are known to have major effects on the risk of an individual for developing the disease. However, there is the potential to reduce the impact of this disease further by preventing disease development. Biomarkers which can either predict the risk for or early stages of colorectal cancer could allow intervention at a time when prospects could be modified by environmental factors, including lifestyle and diet choices. Thus, such biomarkers could be used to identify high risk individuals who would benefit from lifestyle and dietary interventions to prevent this disease. This review will give an overview on one type of biomarker in the form of microRNAs, which have the potential to predict an individual's risk for colorectal cancer, as well as providing a highly sensitive and non-invasive warning of disease presence and/or progression. MicroRNA biomarkers which have been studied and whose levels look promising for this purpose include MiR-18a, MiR-21, MiR-92a, MiR-135b, MiR-760, MiR-601. Not only have several individual microRNAs appeared promising as biomarkers, but panels of these may be even more useful. Furthermore, understanding dietary sources and ways of dietary modulation of these microRNAs might be fruitful in reducing the incidence and slowing the progression of colorectal cancer.

Obesity increases the risk of type 2 diabetes, cardiovascular diseases, and certain cancers, which are among the leading causes of death worldwide. Obesity and obesity-related metabolic diseases are characterized by specific alterations in the human gut microbiota. Experimental studies with gut microbiota transplantations in mice and in humans indicate that a specific gut microbiota composition can be the cause and not just the consequence of the obese state and metabolic disease, which suggests a potential for gut microbiota modulation in prevention and treatment of obesity-related metabolic diseases. In addition, dietary intervention studies have suggested that modulation of the gut microbiota can improve metabolic risk markers in humans, but a causal role of the gut microbiota in such studies has not yet been established. Here, we review and discuss the role of the gut microbiota in obesity-related metabolic diseases and the potential of dietary modulation of the gut microbiota in metabolic disease prevention and treatment.

Energy for fish to carry on with its biological activities and growth comes from food that they eat. In artificial diets, protein become the most expensive source of energy so it is necessary to keep the proportion of protein down to the optimum levels for good growth and feed conversion. In another study, prebiotics resulted in good growth of fish using a manufactured prebiotic supplement. Ideally, we want food material available all year, inexpensive and not be in competition with food material for human consumption. In this study, food formulation with prebiotics made from local products were prepared for fish food. In this study sago was the source of carbohydrates, mackerel and land snails were the source of protein. The formulation was fed to humpback grouper Cromileptes altivelis to study the effectiveness on its growth. Ninety humpback groupers (size 9-9.5 cm, weight 10 – 11 g) were reared in 3 fiberglass tanks for four weeks. Each tank had 30 fish, first tank as control without sago and the two tanks with sago in dietary prebiotic pellet. Length and weight gain were recorded every week then growth performance of fish were assessed in the form of Specific Growth Rate (SGR), Food Conversion Ratio (FCR), weight gain daily and length-weight relationship. Food proximate test were carried out separately in the Integrated Chemistry Laboratory, Institut Pertanian Bogor. Data analysis showed a significant difference in the growth performance of humpback grouper through the values of SGR, FCR and average growth daily, between treatment A and B (with sago) and treatment C (control, zero sago). The proximate test displayed lower protein in treatment A (57.95%) and B (55.95%) but higher in treatment C (59.37%), in the contrary to carbohydrate for treatment A (27.80%), treatment B (26%) and treatment C (22.98%).

Nitro-fatty acids (NO 2 -FA) are pleiotropic modulators of redox signaling pathways. Their effects on inflammatory signaling have been studied in great detail in cell, animal and clinical models primarily using exogenously administered nitro-oleic acid. While we know a considerable amount regarding NO 2 -FA signaling, endogenous formation and metabolism is relatively unexplored. This review will cover what is currently known regarding the proposed mechanisms of NO 2 -FA formation, dietary modulation of endogenous NO 2 -FA levels, pathways of NO 2 -FA metabolism and the detection of NO 2 -FA and corresponding metabolites. Fil: Buchan, Gregory J.. University of Pittsburgh; Estados Unidos Fil: Bonacci, Gustavo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Fazzari, Marco. University of Pittsburgh; Estados Unidos. Fondazione Ri.Med; Italia Fil: Salvatore, Sonia Rosana. University of Pittsburgh; Estados Unidos Fil: Gelhaus Wendell, Stacy. University of Pittsburgh; Estados Unidos

Background Consumption of long-chain polyunsaturated fatty acids (PUFAs), which are abundant in seafood and nuts, ameliorates components of the metabolic syndrome. Circulating microRNAs (miRNAs) have demonstrated to be valuable biomarkers of metabolic diseases. Here, we investigated whether a sustained nuts-enriched diet can lead to changes in circulating miRNAs, in parallel to the dietary modification of fatty acids (FAs). Methods and Results The profile of 192 common miRNAs was assessed (TaqMan low-density arrays) in plasma from 10 healthy women before and after an 8-week trial with a normocaloric diet enriched with PUFAs (30 g/day of almonds and walnuts). The most relevant miRNAs were validated in an extended sample of 30 participants (8 men and 22 women). Adiponectin was measured by immunoassay and FAs by gas liquid chromatography coupled to mass spectrometry. The percentage of both ω-3 ( P =.01) and ω-6 ( P =.029) PUFAs of dietary origin (as inferred from plasma FA concentrations) increased, whereas saturated FAs decreased ( P =.0008). Concomitantly with changes in circulating FAs, several miRNAs were modified by treatment, including decreased miR-328, miR-330-3p, miR-221 and miR-125a-5p, and increased miR-192, miR-486-5p, miR-19b, miR-106a, miR-769-5p, miR-130b and miR-18a. Interestingly, miR-106a variations in plasma correlated with changes in PUFAs, while miR-130b ( r =0.58, P =.003) and miR-221 ( r =0.46, P =.03) reflected changes in C-reactive protein. The dietary modulation of miR-125a-5p mirrored changes in fasting triglycerides ( r =−0.44, P =.019) and increased adiponectin ( r =0.43, P =.026). Conclusion Dietary FAs (as inferred from plasma FA concentration) are linked to changes in circulating miRNAs, which may be modified by a PUFAs-enriched diet.