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Non-alcoholic fatty liver disease (NAFLD) is a rising epidemic affecting around 25% of the global population, in parallel with increasing worldwide rates of obesity and metabolic syndrome. NAFLD is a complex condition with a genetic component shared with other liver or related metabolic disorders. To date, healthy lifestyle modifications based on diet and physical activity are a cornerstone of the NAFLD therapy, where the genetic involvement appears to affect treatment outcomes by interacting with environmental factors. In this context, this research focused on the following objectives: 1) To analyze the association of the SH2B1 rs7359397 gene polymorphism with steatosis severity in subjects with obesity and NAFLD (Chapter 1); 2) To evaluate the influence of the SH2B1 rs7359397 genetic variant on changes in body composition, metabolic status and liver health after 6-month energy-restricted treatment in overweight/obese subjects with NAFLD (Chapter 2); 3) To assess three different genetic risk scores (GRSs) based on Fatty Liver Index (FLI), Magnetic Resonance Imaging (MRI) and lipidomic (OWLiver®-test) for a nutrigenetic personalized management of NAFLD after a 6-months weight-loss nutritional treatment (Chapter 3); and 4) To build a predictive model based on genetic and hepatic health information, deeming insulin resistance markers in order to personalize dietary treatment in overweight/obese subjects with NAFLD (Chapter 4). Regarding the first objective, the results suggested that the risk genotype concerning the SH2B1 rs7359397 genetic variant was associated with higher homeostatic model assessment of insulin resistance, FLI and protein intake. while lower mono- unsaturated fatty acid and fiber intake was found. Moreover, individuals with the minor risk allele also showed a higher susceptibility of advanced stages of NAFLD. Considering the second objective, carriers of the minor allele of the SH2B1 rs7359397 genetic variant showed a better response to a weight-loss dietary intervention in terms of hepatic health and liver status. Furthermore, adherence to Mediterranean dietary pattern rich in fiber and other components such as omega-3 fatty acids might boost these benefits. In relation to the third objective, three GRSs based on different diagnostic tools for detecting NAFLD were able to predict the improvement in liver health after a 6-month energy-restricted nutritional treatment. These associations were particularly influenced by factors such as insulin resistance, inflammatory biomarkers and specific nutrients. Concerning the fourth objective, the designed GRS was able to predict the change in FLI adjusted by diet, age and sex, allowing to personalize the most suitable diet for 72% of the volunteers. Similar models were also able to predict the changes on variables related to insulin resistance depending on diet. In conclusion, new diagnostics and personalized intervention approaches based on nutrigenetics instruments could help to improve precision nutrition management in subjects with NAFLD, reducing the severity, some associated comorbidities and impact on healthcare concerning this disease, as well as explaining the benefits of individualized prescribed dietary patterns.

Neck circumference (NC) and its relationship to height (NHtR) and weight (NWtR) appear to be good candidates for the non-invasive management of non-alcoholic fatty liver disease (NAFLD). This study aimed to evaluate the ability of routine variables to assess and manage NAFLD in 98 obese subjects with NAFLD included in a 2-year nutritional intervention program. Different measurements were performed at baseline, 6, 12 and 24 months. The nutritional intervention significantly improved the anthropometric, metabolic and imaging variables. NC was significantly associated with the steatosis degree at baseline (r = 0.29), 6 m (r = 0.22), 12 m (r = 0.25), and 24 m (r = 0.39) (all p < 0.05). NC was also significantly associated with visceral adipose tissue at all the study time-points (basal r = 0.78; 6 m r = 0.65; 12 m r = 0.71; 24 m r = 0.77; all p < 0.05). NC and neck ratios combined with ALT levels and HOMA-IR showed a good prediction ability for hepatic fat content and hepatic steatosis (at all time-points) in a ROC analysis. The model improved when weight loss was included in the panel (NC-ROC: 0.982 for steatosis degree). NC and ratios combined with ALT and HOMA-IR showed a good prediction ability for hepatic fat during the intervention. Thus, their application in clinical practice could improve the prevention and management of NAFLD.

Nonalcoholic fatty liver disease (NAFLD) prevalence is estimated around 25% worldwide being related to the growing rates of obesity, type 2 diabetes mellitus, and cardiovascular disease. NAFLD onset and progression are complex and have shown relationships with multiple environmental contributors, including unbalanced diets. A link between NAFLD and some psychological traits and inadequate sleep has been suggested, but the nature of these relationships is poorly understood. The current management of NAFLD relies on lifestyle modifications that promote weight loss by means of changes in the diet and/or physical activity. In this context, this research had the following objectives: 1) To evaluate the long-term effects of two personalized energy-restricted dietary strategies on weight loss, anthropometric measurements, biochemical determinations, and hepatic status in subjects with overweight or obesity and NAFLD within a follow-up of 24 months (Chapter 1); 2) To assess the potential relationships of different nutritional factors with hepatic outcomes of individuals with overweight or obesity and NAFLD following personalized energy-restricted dietary strategies (Chapter 2 and 3); 3)To analyze the potential relationships between well-being factors including psychological traits and sleep features with hepatic health markers of individuals with overweight or obesity and NAFLD (Chapter 4 and 5). Regarding the first objective, the results suggested that both dietary strategies may be suitable alternatives for NAFLD management. However, the Fatty Liver in Obesity strategy seemed to provide greater and more persistent metabolic and hepatic benefits. In relation to the second objective, the decrease in liver fat content was associated with a greater weight loss and a higher adherence to the Mediterranean Diet (MedDiet) and dietary Total antioxidant capacity (TAC) after 6 months of intervention. Moreover, the adherence to dietary strategies for 6 months led to changes in erythrocyte membrane omega-3 fatty acid composition, which in turn were associated with changes in hepatic markers (liver stiffness and liver iron content). Concerning the third objective, dietary strategies produced benefits not only in hepatic status but also in depressive and anxiety symptoms, which were positively associated with anthropometric and hepatic determinations. In addition, NAFLD subjects showed poorer sleep features compared to non-NAFLD controls. Likewise, higher sleep disturbances were associated with more probability of having NAFLD, while more sleep disturbances and worse sleep quality were associated with higher values of liver stiffness in NAFLD subjects. In conclusion, healthy energy-restricted dietary strategies with high adherence to MedDiet, as well as TAC and omega-3 fatty acids seem to be effective to improve different metabolic and hepatic markers in subjects with NAFLD. Moreover, beneficial effects on depressive and anxiety symptoms are promoted with these approaches fostering improvements in overall health. In addition to dietary factors, psychological traits and characteristics of sleep pattern should receive attention in the design and implementation of strategies for the prevention and management of NAFLD.

Introducción: la enfermedad de hígado graso no alcohólico (EHGNA) es la patología hepática con mayor prevalencia en la población, caracterizada por la acumulación lipídica e inflamación en los hepatocitos. La vitamina D podría tener un papel beneficioso en EHGNA a través de sus propiedades antiinflamatorias y antifibróticas. Objetivo: revisar la relación entre los niveles sanguíneos de vitamina D y el desarrollo de EHGNA, evaluar los efectos de la suplementación nutricional de vitamina D en los marcadores de afectación hepática y analizar los suplementos y productos alimenticios con vitamina D disponibles en España. Material y Métodos: utilización de la base de datos PubMed como principal fuente bibliográfica mediante la metodología PRISMA, así como la herramienta BotPlus para los complementos alimenticios. Resultados: los pacientes con EHGNA presentan menores niveles sanguíneos de vitamina D en sangre que la población general. La suplementación nutricional con vitamina D ayuda a normalizar sus niveles y disminuye los niveles de marcadores de inflamación (IL-6 y TNF-α), pero no los de enzimas hepáticas. Se observan 455 complementos alimenticios con vitamina D en España, de los cuales un 70% son multivitamínicos, 25% son productos alimenticios y 5% suplementos exclusivos de vitamina D. Conclusiones: la vitamina D podría ser un factor nutricional a considerar en EHGNA, incluyendo la suplementación como una medida adicional a las estrategias nutricionales ya establecidas para esta patología. Introduction: non-alcoholic fatty liver disease (NAFLD) is the most prevalent hepatic pathology in population, characterized by lipid accumulation and inflammation in hepatocytes. Vitamin D could have a beneficial role in NAFLD through anti- inflammatory and antifibrotic features in the liver. Aim: Review the relationship between vitamin D blood levels and NAFLD, evaluate the effects of vitamin D supplementation and hepatic biomarkers and analyse the supplements and nutritional products with vitamin D available in Spain. Material & Methods: Use of database PubMed as the main bibliographic source using PRISMA methodology, as well as BotPlus tool for nutritional products. Results: patients with NAFLD show lower vitamin D blood levels than healthy people. Vitamin D supplementation lowers the levels of inflammatory biomarkers (IL-6 and TNF-α), but not the levels of hepatic enzymes. Conclusions: vitamin D could be a nutritional factor to consider in NAFLD, including supplementation as an additional measure to the nutritional strategies already established for this pathology.

Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. Some genetic variants might be involved in the progression of this disease. The study hypothesized that individuals with the rs7359397 T allele have a higher risk of developing severe stages of NAFLD compared with non-carriers where dietary intake according to genotypes could have a key role on the pathogenesis of the disease. SH2B1 genetic variant was genotyped in 110 overweight/obese subjects with NAFLD. Imaging techniques, lipidomic analysis and blood liver biomarkers were performed. Body composition, general biochemical and dietary variables were also determined. The SH2B1 risk genotype was associated with higher HOMA-IR p equal 0.001; and Fatty Liver Index (FLI) p equal 0.032. Higher protein consumption (p equal 0.028), less mono-unsaturated fatty acid and fiber intake (p equal 0.045 and p equal 0.049, respectively), was also referred to in risk allele genotype. Lipidomic analysis showed that T allele carriers presented a higher frequency of non-alcoholic steatohepatitis (NASH) (69.1/100 vs. 44.4/100; p equal 0.006). In the genotype risk group, adjusted logistic regression models indicated a higher risk of developing an advanced stage of NAFLD measured by FLI (OR 2.91) and ultrasonography (OR 4.15). Multinomial logistic regression models showed that risk allele carriers had higher liver fat accumulation risk (RRR 3.93) and an increased risk of NASH (RRR 7.88). Consequently, subjects carrying the T allele were associated with a higher risk of developing a severe stage of NAFLD. These results support the importance of considering genetic predisposition in combination with a healthy dietary pattern in the personalized evaluation and management of NAFLD.

Introducción: La sarcopenia es un síndrome geriátrico caracterizado por la pérdida progresiva de masa, fuerza y función muscular, reconocido por la Organización Mundial de la Salud como una enfermedad (M62.84). El algoritmo propuesto por el grupo europeo de trabajo sobre la sarcopenia en las personas mayores (EWGSOP) coloca la medición de la fuerza muscular como primer paso para el diagnóstico de sarcopenia, seguido en caso de resultar positivo de la medición de la cantidad y calidad muscular. Hipótesis y objetivos: La hipótesis de este proyecto de investigación es que el estado nutricional y la salud muscular influyen sobre la recuperación tras una fractura de cadera y sobre la mortalidad. Los objetivos específicos de este proyecto de investigación son: (1) Describir cómo el estado nutricional y la intervención nutricional influyen sobre la evolución clínica y la mortalidad; (2) Valorar si la suplementación nutricional oral enriquecida en -hydroxi--metil-butirato (HMB) y vitamina D, mejora la masa muscular y marcadores del estado nutricional; (3) Identificar los factores asociados con la presencia de sarcopenia al ingreso (sarcopenia crónica) y con el desarrollo de sarcopenia durante la estancia hospitalaria (sarcopenia incidente), e investigar la influencia de la sarcopenia sobre el riesgo de mortalidad durante 7 años de seguimiento. Métodos: Para alcanzar los objetivos específicos planteados, se ha realizado una revisión científica, y se han evaluado dos poblaciones específicas: estudio HIPERPROT-GER (intervención hiperproteica en pacientes con fractura de cadera) y estudio PREFISSARC-GER (PREvalencia y FISiopatología de la SARCopenia en pacientes con fractura de cadera). Resultados: En relación al primer objetivo los resultados demuestran que en los pacientes con fractura de cadera la prevalencia de desnutrición es muy alta (siendo casi del 46%), y que esta se asocia con un riesgo aumentado de complicaciones y peor recuperación funcional. La desnutrición, independientemente del criterio utilizado para su definición, se asocia con un aumento de la mortalidad. La intervención nutricional mejora los parámetros nutricionales y se asocia con una mayor recuperación funcional tras la fractura de cadera. En relación al segundo objetivo los resultados obtenidos demuestran que una dieta enriquecida en HMB y vitamina-D mejora la masa muscular, y previene la pérdida de peso en pacientes mayores con fractura de cadera. Respecto al tercer objetivo los factores de riesgo asociados con la sarcopenia incidente y crónica fueron el IMC y el MNA-SF, la fuerza de prensión de la mano y el índice de masa muscular esquelética. Durante el seguimiento, murieron 114 pacientes (sarcopénicos 60,5% vs no sarcopénicos 39,5%, p = 0,001). El análisis de regresión de Cox mostró que los factores asociados con un mayor riesgo de mortalidad fueron la sarcopenia (HR 1,67, IC 95% 1,11-2,51) y la fuerza de prensión disminuida (HR 1,76, IC 95% 1,08-2,88). Conclusiones: La literatura científica pone de manifiesto la alta prevalencia de desnutrición en personas mayores con fractura de cadera. La suplementación nutricional oral enriquecida en HMB y vitamina-D evita la pérdida de peso y mejora la masa muscular en las personas mayores con fractura de cadera. Los pacientes mayores con desnutrición mostraron mayor riesgo de desarrollar sarcopenia durante la estancia hospitalaria. Además los pacientes sarcopénicos presentaron dos veces mayor riesgo de mortalidad que los pacientes no sarcopénicos durante el seguimiento tras una fractura de cadera. Por todo ello podemos concluir que, la prevención de la desnutrición podría contribuir en reducir la incidencia de fractura, que la suplementación nutricional contribuye en prevenir la pérdida de peso y en mejorar la masa muscular tras una fractura de cadera, y en último que la sarcopenia se asocia con un aumento de la mortalidad tras una fractura de cadera.

Obesity is associated to a variety of metabolic disorders and psychological disturbances. The improvement of dietary habits and the promotion of physical activity are the principal strategies to combat obesity. Currently, antioxidants are thoroughly being investigated. Cocoa is one of the richest sources of antioxidants, principally flavanols, with healthy properties to prevent cardiovascular disease, endothelial dysfunctions and oxidative stress. In this context, the principal aim of this investigation was to assess if the daily consumption of 1.4 g of cocoa extract (645 mg of polyphenols with 415 mg of flavanols) within ready‐to‐eat meals and consumed under an energy restricted diet (‐15% E) during 4 weeks, could have beneficial effects on the nutritional and the cardiometabolic status, as well as on depression and anxiety symptoms of middle‐aged overweight/obese subjects. In this sense, the specific objectives were: 1) to analyse the effect of the dietary intervention on general nutrition and metabolism; 2) to assess the effects of cocoa extract consumption on anthropometrics and body composition, blood pressure, routine blood biochemical determinations and biomarkers related to oxidative status, endothelial function and inflammation; 3) to investigate the acute effects of cocoa consumption on blood pressure and blood biochemical markers (0, 60, 120 and 180 min), before and after 4 weeks of daily cocoa consumption; 4) to analyse the effect of cocoa intake within ready‐to‐eat meals on depressive and anxiety symptoms, as well as on the peripheral dopaminergic activity; 5) to evaluate plasma and urinary metabolomic profile in order to assess the presence of cocoa derived metabolites. For that purpose, a 4 week, double‐blind, randomised, placebo‐controlled parallel intervention with a simultaneous postprandial sub‐study was carried out. Fifty subjects were recruited, 25 in each group. The intervention consisted on the daily intake of ready‐to‐eat meals supplemented with 1.4 g of cocoa extract and integrated within a 15% energy restricted diet. At the endpoint, 24 subjects completed the study in the control group and 23 subjects in the cocoa group. This investigation showed that an energy restriction of 15% resulted in beneficial outcomes reducing anthropometric and body composition variables, cardiometabolic markers, inflammatory and oxidative markers, and contributed to the reduction of depressive symptoms. Concerning the inclusion of 1.4 g of cocoa extract, a significantly higher reduction of oxidised low‐density lipoprotein‐cholesterol levels was found in cocoa consumers. However, no difference was demonstrated in the oxidative DNA damage between both groups. Interestingly, the daily consumption of the cocoa extract during 4 weeks revealed a higher reduction of the postprandial systolic blood pressure response compared to the control group, suggesting an adaptive effect over time. On the other hand, the consumption of cocoa extract during 4 weeks did not induce a direct effect on Beck Depression Inventory. However, pHVA, which reflects dopaminergic activity in the brain, showed a greater increase in cocoa consumers compared to the control group. In cocoa group, pHVA was negatively associated with the reduction of depressive symptoms, suggesting the implication of cocoa on psychological behaviour. Finally, the higher presence of cocoa derived metabolites in plasma and urine on cocoa consumers suggested the adequate adherence of the volunteers, as well as the bioavailability of cocoa compounds within the meals.

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. Obesity and unhealthy dietary habits are described as risk factors for NAFLD. The aim of this study was to investigate the association between the consumption of different animal protein sources and hepatic status in NAFLD adults. A total of 112 overweight/obese participants with NAFLD from Fatty Liver in Obesity (FLiO) study were evaluated at baseline. Diet, body composition, and biochemical variables were evaluated. Hepatic status was also assessed by Magnetic Resonance Imaging, ultrasonography, and elastography. Red meat consumption showed a positive relationship with liver iron content (r = 0.224; p = 0.021) and ferritin concentration (r = 0.196; p = 0.037). Processed meat consumption exhibited a positive association with liver iron content (r = 0.308; p = 0.001), which was also found in the quantile regression (β = 0.079; p = 0.028). Fish consumption was related with lower concentration of ferritin (r = -0.200; p = 0.034). This association was further evidenced in the regression model (β = -0.720; p = 0.033). These findings suggest that the consumption of different animal protein sources differentially impact on liver status in obese subjects with NAFLD, showing fish consumption as a healthier alternative for towards NAFLD features.

The preservation of muscle mass and muscle function after weight loss therapy is currently a considerable challenge in the fight against obesity. Muscle mass secretes proteins called myokines that have relevant functions in the regulation of metabolism and health. This study was aimed to evaluate whether a very low-calorie ketogenic (VLCK) diet may modulate myokine levels, in addition to changes in body composition, compared to a standard, balanced low-calorie (LC) diet or bariatric surgery in patients with obesity. Body composition, ketosis, insulin sensitivity and myokines were evaluated in 79 patients with overweight/obesity after a therapy to lose weight with a VLCK diet, a LC diet or bariatric surgery. The follow-up was 6 months. The weight loss therapies induced changes in myokine levels in association with changes in body composition and biochemical parameters. The effects on circulating myokine levels compared to those at baseline were stronger after the VLCK diet than LC diet or bariatric surgery. Differences reached statistical significance for IL-8, MMP2 and irisin. In conclusion, nutritional interventions or bariatric surgery to lose weight induces changes in circulating myokine levels, being this effect potentially most notable after following a VLCK diet.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. NAFLD management is mainly focused on weight loss, but the optimal characteristics of the diet demand further investigation. This study aims to evaluate the effects of two personalized energy-restricted diets on the liver status in overweight or obese subjects with NAFLD after a 6 months follow-up. Ninety-eight individuals from the Fatty Liver in Obesity (FLiO) study were randomized into two groups and followed different energy-restricted diets. Subjects were evaluated at baseline and after 6 months. Diet, anthropometry, body composition, and biochemical parameters were evaluated. Liver assessment included ultrasonography, Magnetic Resonance Imaging, elastography, and determination of transaminases. Both dietary groups significantly improved their metabolic and hepatic markers after the intervention, with no significant differences between them. Multivariate regression models evidenced a relationship between weight loss, adherence to the Mediterranean Diet (MedDiet), and a decrease in liver fat content, predicting up to 40.9% of its variability after 6 months. Moreover, the antioxidant capacity of the diet was inversely associated with liver fat content. Participants in the group with a higher adherence to the MedDiet showed a greater reduction in body weight, total fat mass, and hepatic fat. These results support the benefit of energy-restricted diets, high adherence to the MedDiet, and high antioxidant capacity of the diet for the management of NAFLD in individuals with overweight or obesity.

Background: Olfaction is an important sense influencing food preferences, appetite, and eating behaviors. This hypothesis-driven study aimed to assess associations between olfactory pathway gene methylation signatures, obesity features, and dietary intakes. Methods: A nutriepigenomic analysis was conducted in 474 adults from the Methyl Epigenome Network Association (MENA) project. Anthropometric measurements, clinical data, and serum metabolic profiles of the study population were obtained from structured databases of the MENA cohorts. Habitual dietary intake was assessed using a validated semiquantitative food frequency questionnaire. DNA methylation was measured in circulating white blood cells by microarray (Infinium Human Methylation 450 K BeadChips). FDR values (p < 0.0001) were used to select those CpGs that showed the best correlation with body mass index (BMI) and waist circumference (WC). Pathway analyses involving the characterization of genes involved in the olfactory transduction system were performed using KEGG and pathDIP reference databases. Results: Overall, 15 CpG sites at olfactory pathway genes were associated with BMI (p < 0.0001) and WC (p < 0.0001) after adjustments for potential confounding factors. Together, methylation levels at the15 CpG sites accounted for 22% and 20% of the variability in BMI and WC (r 2 = 0.219, p < 0.001, and r 2 = 0.204, p < 0.001, respectively). These genes encompassed olfactory receptors (OR4D2, OR51A7, OR2T34, and OR2Y1) and several downstream signaling molecules (SLC8A1, ANO2, PDE2A, CALML3, GNG7, CALML6, PRKG1, and CAMK2D), which significantly regulated odor detection and signal transduction processes within the complete olfactory cascade, as revealed by pathway enrichment analyses (p = 1.94 × 10–10). Moreover, OR4D2 and OR2Y1 gene methylation patterns strongly correlated with daily intakes of total energy (p < 0.0001), carbohydrates (p < 0.0001), protein (p < 0.0001), and fat (p < 0.0001). Conclusions: The results of this study suggest novel relationships between olfactory pathway gene methylation signatures, obesity indices, and dietary intakes.

Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of liver disease in the Western world, affecting up to 20-30% of the general adult population. It is a growing public health problem, because of the increasing prevalence of the pathologies that contribute to its development such as obesity and inflammation status. The diagnostic method of choice for NAFLD is liver biopsy, but since it is a long-standing disease, it is difficult to follow large population groups through serial biopsies. Therefore, it is necessary to identify noninvasive liver damage tools that facilitate the diagnosis and prognosis of the disease and allow for the establishment of a follow-up protocol that prevents progression to severe stages of NAFLD. Moreover, the main therapeutic basis is the modification of lifestyle through diet and exercise In this context, this research work aimed: 1) to assess the possible association between a validated Dietary Inflammatory Index (DII) and specific dietary components with suitable non-invasive markers of liver status in overweight/obese subjects with cardiovascular risk; 2) to evaluate the influence of two energy-restricted diets on non-invasive markers and scores of liver damage in overweight/obese individuals with features of metabolic syndrome after six months of follow-up and to assess the role of fiber content in metabolic outcomes; 3) to assess the influence of weight loss on lysophospholipid metabolism and liver status in overweight/obese subjects as well as to provide new evidence regarding the interaction of lysophospholipids metabolism as a key factor in the onset and management of obesity-related diseases such as liver damage; 4) to analyze the response of FGF-21 after a weight loss intervention and the relationships with other putative inflammatory liver biomarkers; 5) to evaluate the fatty liver status by several validated approaches and to compare imaging techniques, lipidomic and routine blood markers with magnetic resonance imaging (MRI) in adults subjects with NAFLD. In relation with the first objective, the results of this chapter evidended that the consumption of an anti-inflammatory dietary pattern might contribute to the reduction of obesity and related comorbidities, especially NAFLD through precision nutrition guidelines. Concerning the second objective, we concluded that the design of dietary patterns based on the consumption of insoluble fiber and fiber from fruits in the context of energy restriction is a good choice the management of obese patients suffering from NAFLD. The third chapter suggested a generalized decrease in circulating lysophospholipids (LP), particularly lysophosphatidylcholine, after a weight loss intervention in a population with metabolic syndrome features. Changes in fatty liver index, waist circumference and BAAT score revealed positive association with lysophosphatidylcholine score. The involvement of particular LP in liver metabolism and obesity merits further attention. The fourth chapter revealed that FGF-21 changes exhibit a great association with non-alcoholic fatty liver inflammation, M30 fragment and PAI-I, independently of weight loss. These findings suggest that FGF-21 is involved in the obesity-inflammation-liver process. Finally, in relation to the fifth objective we concluded that ultrasonography, a metabolomic test and a panel combination including routine blood markers linked to insulin resistance showed the highest associations with MRI, which is considered the gold standard for non-invasive liver fat content assessment, suggesting these tools could contribute to the diagnosis and prognosis of NAFLD.

The relevance of sleep patterns in the onset or evolution of nonalcoholic fatty liver disease (NAFLD) is still poorly understood. Our aim was to investigate the association between sleep characteristics and hepatic status indicators in obese people with NAFLD compared to normal weight non-NAFLD controls. Ninety-four overweight or obese patients with NAFLD and 40 non-NAFLD normal weight controls assessed by abdominal ultrasonography were enrolled. Hepatic status evaluation considered liver stiffness determined by Acoustic Radiation Force Impulse elastography (ARFI) and transaminases. Additionally, anthropometric measurements, clinical characteristics, and biochemical profiles were determined. Sleep features were evaluated using the Pittsburgh Sleep Quality Index (PSQI). Hepatic status parameters, anthropometric measurements, and clinical and biochemical markers differed significantly in NAFLD subjects compared to controls, as well as sleep efficiency, sleep disturbance score, and sleep quality score. In the NAFLD group, a higher prevalence of short sleep duration (p = 0.005) and poor sleep quality (p = 0.041) were found. Multivariate-adjusted odds ratio (95% confidence interval) for NAFLD considering sleep disturbance was 1.59 (1.11–2.28). Regression models that included either sleep disturbance or sleep quality predicted up to 20.3% and 20.4% of the variability of liver stiffness, respectively, and after adjusting for potential confounders.Current findings suggest that sleep disruption may be contributing to the pathogenesis of NAFLD as well as the alteration of the liver may be affecting sleep patterns. Consequently, sleep characteristics may be added to the list of modifiable behaviors to consider in health promotion strategies and in the prevention and management of NAFLD.

Malnutrition is very prevalent in geriatric patients with hip fracture. Nevertheless, its importance is not fully recognized. The objective of this paper is to review the impact of malnutrition and of nutritional treatment upon outcomes and mortality in older people with hip fracture. We searched the PubMed database for studies evaluating nutritional aspects in people aged 70 years and over with hip fracture. The total number of studies included in the review was 44, which analyzed 26,281 subjects (73.5% women, 83.6 +/- 7.2 years old). Older people with hip fracture presented an inadequate nutrient intake for their requirements, which caused deterioration in their already compromised nutritional status. The prevalence of malnutrition was approximately 18.7% using the Mini-Nutritional Assessment (MNA) (large or short form) as a diagnostic tool, but the prevalence was greater (45.7%) if different criteria were used (such as Body Mass Index (BMI), weight loss, or albumin concentration). Low scores in anthropometric indices were associated with a higher prevalence of complications during hospitalization and with a worse functional recovery. Despite improvements in the treatment of geriatric patients with hip fracture, mortality was still unacceptably high (30% within 1 year and up to 40% within 3 years). Malnutrition was associated with an increase in mortality. Nutritional intervention was cost effective and was associated with an improvement in nutritional status and a greater functional recovery. To conclude, in older people, the prevention of malnutrition and an early nutritional intervention can improve recovery following a hip fracture.

Background: Dietary total antioxidant capacity (TAC), glycemic index (GI), and glycemic load (GL) are accepted indicators of diet quality, which have an effect on diet–disease relationships. The aim of this study was to evaluate potential associations of dietary TAC, GI, and GL with variables related to nutritive status and insulin resistance (IR) risk in cardiometabolic subjects. Methods: A total of 112 overweight or obese adults (age: 50.8 ± 9 years old) were included in the trial. Dietary intake was assessed by a validated 137-item food frequency questionnaire (FFQ), which was also used to calculate the dietary TAC, GI, and GL. Anthropometrics, blood pressure, body composition by dual-energy X-ray absorptiometry (DXA), glycemic and lipid profiles, C-reactive protein (CRP), as well as fatty liver quantification by magnetic resonance imaging (MRI) were assessed. Results: Subjects with higher values of TAC had significantly lower circulating insulin concentration and homeostatic model assessment of insulin resistance (HOMA-IR). Participants with higher values of HOMA-IR showed significantly higher GI and GL. Correlation analyses showed relevant inverse associations of GI and GL with TAC. A regression model evidenced a relationship of HOMA-IR with TAC, GI, and GL. Conclusion: This data reinforces the concept that dietary TAC, GI, and GL are potential markers of diet quality, which have an impact on the susceptible population with a cardiometabolic risk profile.

Background: Non-coding RNAs (i.e., miRNAs) play a role in the development of obesity and related comorbidities and the regulation of body weight. Objective: To identify candidate miRNA biomarkers throughout omics approaches in order to predict the response to specific weight-loss dietary treatments. Design: Genomic DNA and cDNA isolated from white blood cells of a subset from the RESMENA nutritional intervention study (Low-responders (LR) vs High-responders (HR)) was hybridized in Infinium Human Methylation450 BeadChip and in Illumina Human HT-12 v4 gene expression BeadChips arrays respectively. A bioinformatic prediction of putative target sites of selected miRNAs was performed by applying miRBase algorithms. HEK-293T cells were co-transfected with expression vectors containing the 3'-UTR of candidate genes to validate the binding of miRNAs to its target sites. Results: 134 miRNAs were differentially methylated between HR and LR in the methylation array, whereas 44 miRNAs were differentially expressed between both groups in the expression array. Specifically, miR-1237, miR-1976, miR-642, miR-636, miR-612 and miR-193B were simultaneously hypomethylated and overexpressed in HR. miR-612 and miR-1976 showed greatest differences in methylation and expression levels, respectively. The bioinformatic prediction revealed that TP53 was a putative target gene of miR-612 and CD40 of miR-1976. Moreover, TP53 was downregulated in the expression array when comparing HR vs LR expression levels adjusted by sex, diet, age and baseline weight, and CD40 showed a statistical trend. Furthermore, gene expression levels of TP53 and CD40 in white blood cells, when measured by qPCR, were also downregulated in HR. Finally, miR-612 and miR-1976 potently repressed TP53 and CD40 respectively by targeting its 3'-UTR regions. Conclusion: miR-612 and miR-1976 levels could be prospective biomarkers of response to specific weight-loss diets and might regulate the gene expression of TP53 and CD40.

The aim of this study was to evaluate whether genome-wide levels of DNA methylation are associated with age and the health risks of obesity (HRO); defined according to BMI categories as “Low HRO” (overweight and class 1 obesity) versus “High HRO” (class 2 and class 3 obesity). Anthropometric measurements were assessed in a subsample of 48 volunteers from the Metabolic Syndrome Reduction in Navarra (RESMENA) study and 24 women from another independent study, Effects of Lipoic Acid and Eicosapentaenoic Acid in Human Obesity (OBEPALIP study). In the pooled population; the methylation levels of 55 CpG sites were significantly associated with age after Benjamini-Hochberg correction. In addition, DNA methylation of three CpG sites located in ELOVL2; HOXC4 and PI4KB were further negatively associated with their mRNA levels. Although no differentially methylated CpG sites were identified in relation to HRO after multiple testing correction; several nominally significant CpG sites were identified in genes related to insulin signaling; energy and lipid metabolism. Moreover, statistically significant associations between BMI or mRNA levels and two HRO-related CpG sites located in GPR133 and ITGB5 are reported. As a conclusion, these findings from two Spanish cohorts add knowledge about the important role of DNA methylation in the age-related regulation of gene expression. In addition; a relevant influence of age on DNA methylation in white blood cells was found, as well as, on a trend level, novel associations between DNA methylation and obesity.

The present research evaluated circulating betatrophin levels in obese patients with metabolic syndrome features under energy-restricted weight-loss programs and in normal weight in order to stablish the putative interplay between the levels of this hormone, diet and metabolic risk factors linked to obesity and associated comorbidities.

El tribunal de esta tesis estuvo constituido por: - Dr. D. Salvador Zamora Navarro, Catedrático de Fisiología, Universidad de Murcia. - Dr. D. Miguel Ángel Martínez González, Catedrático de Medicina Preventiva y Salud Pública, Universidad de Navarra. - Dr. D. João Joaquim Rodrigues da Silva Breda, Investigador, WHO Regional Office for Europe - Dr Dª. Itziar Abete, Investigadora, Instituto de Investigación Sanitaria Biodonostia. - Dr Dª. María Teresa Macarulla Arenaza, Profesora Titular de Nutrición y Bromatología, Universidad del País Vasco. The rates of non-communicable diseases have reached epidemic proportions worldwide, with obesity and psychological disorders being among the most prevalent. The main purpose of this research was to determine the possible metabolic and epigenetic mechanisms behind weight loss in overweight individuals after following different energy-restricted diets, as well as evaluating the impact of the dietary treatments on symptoms of depression and anxiety disorders. To follow a hypocaloric diet designed to reduce metabolic syndrome (MetS) features was effective for decreasing depressive and anxiety symptoms in middle-aged subjects. The decrease in depressive manifestations was positively related to body weight and fat mass changes, as well as with the decrease in C-reactive protein (CRP), malondialdehyde (MDA) and leptin blood levels and with a higher folate intake during the intervention. In contrast, decline in anxiety symptoms was parallel to a greater decrease in body weight, body mass index (BMI), waist circumference and fat mass. Moreover, a positive cross-sectional association between a healthy dietary pattern and intake of some specific nutrients (water, fibre, vitamin B6, ascorbic acid, tryptophan, magnesium and selenium) with mood state was found. In addition, a negative relationship between depressive symptoms and consumption of omega-3 polyunsaturated fatty acids (PUFAs) was evidenced in middle-aged subjects with MetS. Interestingly, an increase in serotonin and dopamine (DA) blood levels after the weight loss treatment in obese patients with MetS was demonstrated, being this increase related with lower energy and carbohydrates intakes, respectively. Furthermore, in overweight and obese older adults baseline palmitoleic acid (C16:1) concentrations were found to be negative predictor of changes in adiposity, while baseline DA and serotonin receptor 2A (HTR2A) methylation levels were hypothesized as new biomarkers for the response to a nutritional intervention in subjects with MetS. In summary, this thesis provides further insights regarding emotional and metabolic factors behind body weight reduction after following different dietary treatments for weight loss in overweight and obese older adults as well as in middle-aged subjects with MetS.

Understanding the regulation of gene activities depending on DNA methylation has been the subject of much recent study. However, although polymorphisms of the HTR2A gene have been associated with both obesity and psychiatric disorders, the role of HTR2A gene methylation in these illnesses remains uncertain. The aim of this study was to evaluate the association of HTR2A gene promoter methylation levels in white blood cells (WBC) with obesity traits and depressive symptoms in individuals with metabolic syndrome (MetS) enrolled in a behavioural weight loss programme. Analyses were based on 41 volunteers (mean age 49 ± 1 year) recruited within the RESMENA study. Depressive symptoms (as determined using the Beck Depression Inventory), anthropometric and biochemical measurements were analysed at the beginning and after six months of weight loss treatment. At baseline, DNA from WBC was isolated and cytosine methylation in the HTR2A gene promoter was quantified by a microarray approach. In the whole-study sample, a positive association of HTR2A gene methylation with waist circumference and insulin levels was detected at baseline. Obesity measures significantly improved after six months of dietary treatment, where a lower mean HTR2A gene methylation at baseline was associated with major reductions in body weight, BMI and fat mass after the treatment. Moreover, mean HTR2A gene methylation at baseline significantly predicted the decrease in depressive symptoms after the weight loss treatment. In conclusion, this study provides newer evidence that hypermethylation of the HTR2A gene in WBC at baseline is significantly associated with a worse response to a weight-loss intervention and with a lower decrease in depressive symptoms after the dietary treatment in subjects with MetS.

This study presents a new dietary strategy, the RESMENA diet, to combat the comorbidities of the MetS and compares it with following a diet based on the AHA guidelines. The RESMENA diet proved to be more effective throughout a self-control period, where the participants had to apply on their own previous acquired dietary habits, regarding body composition, especially central obesity, and by reducing transaminase levels and maintaining uric acid and serum glucose levels in patients with MetS. Among people suffering MetS with hyperglycaemia, the RESMENA diet showed more benefits than the AHA diet concerning android fat mass reduction and improvement of the general oxidative stress status. Moreover, this investigation evidenced how fibre, TAC, vitamin C, tocopherols, lycopene and fruits are the dietary components that most contributed to improve the MetS related parameters. Furthermore, a link between the recently discovered myokine irisin and several lipid profile biomarkers was reported, suggesting a response of this myokine to atherogenic burdens or a resistance phenomenon. Finally, different dietary antioxidants were proposed to enhance the PON1 ARE activity by epigenetic regulation, lowering the PON1 gene methylation levels.

Background and aims Cocoa flavanols are recognised by their favourable antioxidant and vascular effects. This study investigates the influence on health of the daily consumption of ready-to-eat meals supplemented with cocoa extract within a hypocaloric diet, on middle-aged overweight/obese subjects. Methods and results Fifty healthy male and female middle-aged volunteers [57.26 ± 5.24 years and body mass index (BMI) 30.59 ± 2.33 kg/m2] were recruited to participate in a 4 week randomised, parallel and double-blind study. After following 3 days on a low-polyphenol diet, 25 volunteers received meals supplemented with 1.4 g of cocoa extract (645.3 mg of polyphenols) and the other 25 participants received control meals, within a 15% energy restriction diet. On the 4th week of intervention individuals in both dietary groups improved (p < 0.05) anthropometric, body composition, blood pressure and blood biochemical measurements. Oxidised LDL cholesterol (oxLDL), showed a higher reduction (p = 0.030) in the cocoa group. Moreover, myeloperoxidase (MPO) levels decreased only in the cocoa supplemented group (p = 0.007). Intercellular Adhesion Molecule-1 (sICAM-1) decreased significantly in both groups, while Vascular Cell Adhesion Molecule-1 (sVCAM-1) did not present differences after the 4 weeks of intervention. Interestingly, cocoa intake showed a different effect by gender, presenting more beneficial effects in men. Conclusions The consumption of cocoa extract as part of ready-to-eat meals and within a hypocaloric diet improved oxidative status (oxLDL) in middle-aged subjects, being most remarkable in males.

The application of metabolomics in nutritional research may be a useful tool to analyse and predict the response to a dietary intervention. The aim of this study was to examine metabolic changes in serum samples following exposure to an energy-restricted diet (-15% of daily energy requirements) over a period of 8weeks in overweight and obese older adults (n=22) using a gas chromatography/mass spectrometry (GC/MS) metabolomic approach. After 8weeks, there were significant reductions in weight (7%) and metabolic improvement (glucose and lipid profiles). Metabolomic analysis found that total saturated fatty acids (SFAs), including palmitic acid (C16:0) and stearic acid (C18:0) and monounsaturated fatty acids (MUFAs), were significantly decreased after the 8-week intervention. Furthermore, palmitoleic acid (C16:1) was found to be a negative predictor of change in body fat loss. Both the total omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) significantly decreased, although the overall total amounts of PUFAs did not. The branched chain amino acid (BCAA) isoleucine significantly decreased in the serum samples after the intervention. In conclusion, this study demonstrated that the weight loss intervention based on a hypocaloric diet identified changes in the metabolic profiles of serum in overweight and obese older adults, with a reduction in anthropometric and biochemical parameters also found.

BACKGROUND: Metabolic syndrome (MetS) and depression have become two prevalent diseases worldwide, whose interaction needs further investigation. Dietary treatment for weight loss in patients with MetS may improve depressive manifestations, however, the precise interactive pathways remain uncertain. Therefore, the aim of this study was to examine the effects of a hypocaloric diet designed to reduce MetS features on self-perceived depression and the possible underlying factors. METHODS: Sixty subjects (Age:50 +/- 1 y; BMI:36.1 +/- 0.6 kg/m2) with MetS were selected from the RESMENA study (control and intervention) after they completed the 6-months hypocaloric treatment and rated for depressive symptoms using the Beck Depression Inventory (BDI). Anthropometric and biochemical measurements including leptin, C-reactive protein (CRP) and insulin levels were evaluated. RESULTS: Depressive symptoms decreased during the weight loss intervention, with no differences between both dietary groups (control group -4.2 +/- 0.8 vs RESMENA group -3.2 +/- 0.6, P = 0.490). The number of criteria of the MetS was higher among subjects with more somatic-related depressive symptoms at baseline (B = 1.032, P-trend = 0.017). After six months of dietary treatment, body weight decreased in all subjects (-8.7%; confidence interval (95%CI) = 7.0-9.7) and also self-perceived depression (-37.9%; 95%CI = 2.7-4.9), as well as circulating leptin (-20.1%; 95%CI = 1.8-6.8), CRP (-42.8%; 95%CI = 0.6-3.0) and insulin (-37.7%; 95%CI = 4.1-7.2) concentrations. The decrease in BDI was significantly associated with declines in body fat mass (B = 0.34, 95%CI = 0.11-0.56) and also with the decrease in leptin (B = 0.16, 95%CI = 0.04-0.28) and CRP (B = 0.24, 95%CI = 0.01-0.46) concentrations. CONCLUSIONS: The decrease in depressive manifestations after a weight loss intervention was related with adiposity, CRP and leptin in subjects with MetS.

Objective A recently discovered myokine, irisin, may have an important role in energy metabolism. This study aimed to evaluate the relationship between this hormone and the lipid profile of Metabolic Syndrome (MetS) patients following a hypocaloric diet. Design Ninety-three Caucasian adults (52 men/41 women) diagnosed with MetS followed an 8-week-long energy restricted programme (-30% of the energy requirements). Anthropometric measurements, biochemical markers and plasma irisin levels were analysed before and after the nutritional intervention. Results Global plasma irisin levels were significantly reduced at the end of the study (-72•0 ± 100•9 ng/mL, p < 0•001) accompanying the weight loss (-6•9%). The depletion of irisin significantly correlated with changes in some atherogenic-related variables: total cholesterol (B = 0•106, p = 0•018), total cholesterol/high density lipoprotein-cholesterol ratio (B = 0•002, p = 0•036), low density lipoprotein-cholesterol (B = 0•085, p = 0•037) and apolipoprotein B (B = 0•052, p = 0•002), independently of changes in body weight. Conclusions An association between the reduction of plasma irisin levels and the depletion of important lipid metabolism biomarkers was observed in patients with MetS undergoing an energy restricted programme.

Obesity and metabolic syndrome (MetS) have become major public health problems worldwide. Dietary strategies represent the primary choice treatment. The aim of this study was to investigate the effect of a new energy-restricted dietary strategy (RESMENA) involving different dietary aspects such us a modified macronutrient profile including a moderately increased amount of proteins, an augmented meal frequency, an enhancement of low GI/GL and high antioxidant content food and with a high adherence to the Mediterranean Diet, on anthropometric, biochemical and inflammatory markers in obese subjects presenting MetS features after a nutritional intervention of 8 weeks duration. Additionally, the effectiveness of the RESMENA diet was compared with a pattern based on the American Heart Association (AHA) guidelines and potential underlying mechanisms such us hormonal influences and epigenetic modifications were studied. It was observed that the two dietary plans were equally effective on improving anthropometric and biochemical markers. Dietary total antioxidant capacity was evidenced as the major influential element given that several anthropometric and biochemical indicators were influenced by it. Moreover, the AHA-based pattern showed to be more beneficial in order to improve the inflammation status (CRP, PAI-1, TNF-α, IL-6) associated to obesity, at least in the short-term and it was observed an association between protein intake and the inflammation condition. Interestingly, animal origin protein as a whole, and meat derived protein showed to negatively influence the inflammatory status. However associations were found neither for vegetal origin protein, nor for fish. Subsequently, the new recently discovered myokine irisin was studied. It was observed that irisin plasma concentrations decreased after following the energy-restricted dietary patterns, without differences between them, in association with body weight reduction. Then, it was evidenced that irisin levels were associated with the changes in glucose homeostasis parameters, being greater the reductions on glucose, insulin and HOMA index among the participants with higher irisin baseline levels. Finally, DNA methylation of SERPINE1 gene, which codes for PAI-1, was assessed and it was observed that the higher methylation levels at baseline, the greater reductions were observed in some obesity indicators. In summary, these data evidenced the effectiveness of a new dietary pattern and the influence of specific dietary components on anthropometric, biochemical and inflammatory markers of obese subjects with MetS after an intervention of 8-weeks duration. Furthermore, the influence of the recently discovered irisin and the epigenetics modifications have been ¿manifested as influential in mediating the obtained outcomes.

PURPOSE: Dietary food composition influences postprandial glucose homeostasis. Thus, the objective was to investigate the effects of an acute intake of three different types of strawberry jam, differing in carbohydrate and antioxidants content, on postprandial glucose metabolism, lipid profile, antioxidant status, and satiety. METHODS: Sixteen healthy adults participated in a randomized, crossover, double-blind study with three arms, receiving 60 g of three different strawberry jams. Blood samples were collected at fasting and at 30, 60, 90, and 120 min after its intake. Blood analyses were performed with validated procedures and satiety was estimated with visual analogue scale (VAS). RESULTS: Blood glucose concentrations were maintained at normal values and without peaks within the 2 h after consumption of low-sugar jams. However, blood glucose and insulin were significantly higher at 30 and 60 min after high-sugar (HS) jam intake versus both low-sugar jams. Furthermore, HS jam produced more satisfaction at short time, but decreased as soon as blood glucose concentration began to decrease. Moreover, HS ingestion produced lower free fatty acid levels (p < 0.05) throughout the trial with respect both the low-sugar jams. However, no additional benefits on oxidative status (malondialdehyde, glutathione peroxidase, total antioxidant capacity, and uric acid), glucose, lipid, and satiety variables were observed due to the inclusion of an antioxidant to low-sugar jam. CONCLUSIONS: This study reinforces the idea that products without added sugars are appropriate for the management of glycemic alterations and provides further insight into the effect of natural antioxidants as a functional ingredient on oxidative status and related metabolic disturbances.

BACKGROUND: Despite oxidized low density lipoprotein (ox-LDL) plays important roles in the pro-inflammatory and atherosclerotic processes, the relationships with metabolic and oxidative stress biomarkers have been only scarcely investigated in young adult people. Thus, the aim of this study was to assess plasma ox-LDL concentrations and the potential association with oxidative stress markers as well as with anthropometric and metabolic features in healthy young adults. METHODS: This study enrolled 160 healthy subjects (92 women/68 men; 23±4 y; 22.0±2.9 kg/m2). Anthropometry, body composition, blood pressure, lifestyle features, biochemical data, and oxidative stress markers were assessed with validated tools. Selenium, copper, and zinc nail concentrations were measured by atomic absorption spectrophotometry. RESULTS: Total cholesterol (TC), LDL-c and uric acid concentrations, TC-to-HDL-c ratio, and glutathione peroxidase (GPx) activity were positive predictors of ox-LDL concentrations, while nail selenium level (NSL) was a negative predictor, independently of gender, age, smoking status, physical activity. Those individuals included in the highest tertile of GPx activity (≥611 nmol/[mL/min]) and of NSL (≥430 ng/g of nail) had higher and lower ox-LDL concentrations, respectively, independently of the same covariates plus truncal fat or body mass index, and total cholesterol or LDL-c concentrations. CONCLUSIONS: Ox-LDL concentrations were significantly associated with lipid biomarkers, GPx activity, uric acid concentration, and NSL, independently of different assayed covariates, in young healthy adults. These findings jointly suggest the early and complex relationship between lipid profile and redox status balance.

BACKGROUND: Dietary total antioxidant capacity (TAC) has been assumed as a useful tool to assess the relationship between the cumulative antioxidant food capacity and several chronic disorders. The aim of this cross-sectional study was to investigate the potential relationships of dietary TAC with adiposity, metabolic and oxidative stress markers in healthy young adults. METHODS: This study enrolled 266 healthy subjects (105 men/ 161 women; 22 ± 3 years-old; 22.0 ± 2.7 kg/m2). Dietary intake, anthropometry, blood pressure, lifestyle features, and biochemical data were assessed with validated procedures. RESULTS: In linear regression analyses, dietary TAC values were inversely associated with glycemia, total cholesterol:HDL-c ratio, triglycerides and oxidized-LDL concentrations, and positively associated with HDL-c concentrations, independently of gender, age, smoking status, physical activity, vitamin use supplement, waist circumference, energy intake, fatty acid intake. In addition, plasma TAC was negatively correlated with ox-LDL concentrations (r= -0.20, P = 0.003), independently of the assessed confounding variables. Finally, dietary TAC values were inversely related to waist circumference values (r= -0.17, P = 0.005) as well as to lower mild central obesity occurrence (waist circumference ≥ 80/ 94 cm for women/ men, respectively). CONCLUSION: Dietary TAC values are inversely associated with glucose and lipid biomarkers as well as with central adiposity measurements in healthy young adults, indicating dietary TAC as a useful tool to assess the health benefits of cumulative antioxidant capacity from food intake. In addition, the independent and inverse relationships of ox-LDL concentrations with dietary and plasma TAC respectively suggest a putative role of antioxidant rich-diet in the link between redox state and atherogenesis at early stage.

Epigenetics could help to explain individual differences in weight loss after an energy-restriction intervention. Here, we identify novel potential epigenetic biomarkers of weight loss, comparing DNA methylation patterns of high and low responders to a hypocaloric diet. Twenty-five overweight or obese men participated in an 8-wk caloric restriction intervention. DNA was isolated from peripheral blood mononuclear cells and treated with bisulfite. The basal and endpoint epigenetic differences between high and low responders were analyzed by methylation microarray, which was also useful in comparing epigenetic changes due to the nutrition intervention. Subsequently, MALDI-TOF mass spectrometry was used to validate several relevant CpGs and the surrounding regions. DNA methylation levels in several CpGs located in the ATP10A and CD44 genes showed statistical baseline differences depending on the weight-loss outcome. At the treatment endpoint, DNA methylation levels of several CpGs on the WT1 promoter were statistically more methylated in the high than in the low responders. Finally, different CpG sites from WT1 and ATP10A were significantly modified as a result of the intervention. In summary, hypocaloric-diet-induced weight loss in humans could alter DNA methylation status of specific genes. Moreover, baseline DNA methylation patterns may be used as epigenetic markers that could help to predict weight loss.

Introduction: The high prevalence of metabolic syndrome (MS) in Spain requires additional efforts for prevention and treatment. Objective: The study RESMENA-S aims to improve clinical criteria and biomarkers associated with MS though an integral therapy approach. Methods: The study is a randomized prospective parallel design in which is expected to participate a total of 100 individuals. The RESMENA-S group (n = 50) is a personalized weight loss (30% energy restriction) diet, with a macronutrient distribution (carbohydrate / fat / protein) of 40/30/30, high meal frequency (7 / day), low glycemic index/load and high antioxidant capacity as well as a high adherence to the Mediterranean diet. The control group (n = 50) is assigned to a diet with the same energy restriction and based on the American Heart Association pattern. Both experimental groups are under dietary and psychological control during 8 weeks. Likewise, for an additional period of 16 weeks of self-control, is expected that volunteers will follow the same pattern but with no dietary advice. Results: Anthropometrical data and body composition determinations as well as blood and urine samples are being collected at the beginning and end of each phase. This project is registered at www.clinicaltrials.gov with the number NCT01087086 and count with the Research Ethics Committee of the University of Navarra approval (065/2009). Conclusions: Intervention trials to promote the adoption of dietary patterns and healthy lifestyle are of great importance to identify the outcomes and nutritional mechanisms that might explain the link between obesity, metabolic syndrome and associated complications.

Background: Obesity is the most relevant overnutrition disease worldwide and is associated to different metabolic disorders such as insulin resistance and type-2 diabetes. Low glycemic load foods and diets and moderately high protein intake have been shown to reduce body weight and fat mass, exerting also beneficial effects on LDL-cholesterol, triglyceride concentrations, postprandial glucose curve and HDL-cholesterol levels. The present study aimed at studying the potential functionality of a series of low glycemic index products with moderately high protein content, as possible coadjuvants in the control of type-2 diabetes and weight management following a chronologically planned snacking offer (morning and afternoon). Methods: The current trial followed a single group, sequential, longitudinal design, with two consecutive periods of 4 weeks each. A total of 17 volunteers participated in the study. The first period was a free living period, with volunteers' habitual ad libitum dietary pattern, while the second period was a free-living period with structured meal replacements at breakfast, morning snack and afternoon snack, which were exchanged by specific products with moderately high protein content and controlled low glycemic index, following a scheduled temporal consumption. Blood extractions were performed at the beginning and at the end of each period (free-living and intervention). Parameters analysed were: fasting glucose, insulin, glycosylated hemoglobin, total-, HDL- and LDL-cholesterol, triglyceride, C - reactive protein and Homocysteine concentrations. Postprandial glucose and insulin were also measured. Anthropometrical parameters were monitored each 2 weeks during the whole study. Results: A modest but significant (p = 0.002) reduction on body weight (1 kg) was observed during the intervention period, mainly due to the fat mass loss (0.8 kg, p = 0.02). This weight reduction was observed without apparently associated changes in total energy intake. None of the biochemical biomarkers measured was altered throughout the whole study. Conclusions: Small changes in the habitual dietary recommendations in type-2 diabetes patients by the inclusion of specific low-glycemic, moderately high-protein products in breakfast, morning and afternoon snacks may promote body weight and fat-mass loss, without apparently altering biochemical parameters and cardiovascular risk-related factors.

This study assessed the potential association of some proinflammatory markers with adiposity (total vs. central) and metabolic features in young adults. Measurements included body composition, lifestyle features, blood biochemical, and selected inflammatory indicators on 154 healthy subjects (53 M/101 F; 21.5 ± 3 years; 22.1 ± 2.6 kg/m(2)). Those subjects with higher waist circumference (WC) and waist-hip ratio (WHR) showed higher (P

Dietary antioxidant intake has been suggested to protect against oxidative damage and related clinical complications. The aim of this study was to assess the potential relationships between the dietary total antioxidant capacity (TAC) and obesity-related features in children and adolescents. Anthropometric variables from 369 children and adolescents were measured (184 obese and 185 control). A validated food-frequency questionnaire was used to calculate the TAC and the daily nutrient and energy intake. Dietary TAC showed positive associations with fiber, folic acid, magnesium, and vitamins A, C and E. BMI, SDS-BMI and total body fat were inversely associated with dietary TAC only in obese subjects. These data suggest that dietary TAC may be a potential indicator of the risk to develop obesity-related features and could be considered as a useful method in assessing antioxidant intake.

BACKGROUND: Fruits and vegetables are important sources of fiber and nutrients with a recognized antioxidant capacity, which could have beneficial effects on the proinflammatory status as well as some metabolic syndrome and cardiovascular disease features. The current study assessed the potential relationships of fruit and vegetable consumption with the plasma concentrations and mRNA expression values of some proinflammatory markers in young adults. METHODS: One-hundred and twenty healthy subjects (50 men/70 women; 20.8 +/- 2.6 y; 22.3 +/- 2.8 kg/m2) were enrolled. Experimental determinations included anthropometry, blood pressure and lifestyle features as well as blood biochemical and inflammatory measurements. The mRNA was isolated from peripheral blood mononuclear cells (PBMC) and the gene expression concerning selected inflammatory markers was assessed by quantitative real-time PCR. Nutritional intakes were estimated by a validated semi-quantitative food-frequency questionnaire. RESULTS: The highest tertile of energy-adjusted fruit and vegetable consumption (>660 g/d) was associated with lower plasma concentrations of C-reactive protein (CRP) and homocysteine and with lower ICAM1, IL1R1, IL6, TNFalpha and NFkappaB1 gene expression in PBMC (P for trend < 0.05), independently of gender, age, energy intake, physical activity, smoking, body mass index, systolic blood pressure and circulating non-esterified fatty acids. In addition, plasma CRP, homocysteine and TNFalpha concentrations and ICAM1, TNFalpha and NFkappaB1 gene expression in PBMC showed a descending trend as increased fiber intake (>19.5 g/d) from fruits and vegetables (P for trend < 0.05). Furthermore, the participants within the higher tertile (>11.8 mmol/d) of dietary total antioxidant capacity showed lower plasma CRP and mRNA values of ICAM1, IL1R1, IL6, TNFalpha and NFkappaB1 genes (P for trend < 0.05). The inverse association between fruit and vegetable consumption and study proinflammatory markers followed the same trend and remained statistically significant, after the inclusion of other foods/nutrients in the linear regression models. CONCLUSION: A higher fruit and vegetable consumption was independently associated not only with reduced CRP and homocysteine concentrations but also with a lower mRNA expression in PBMC of some relevant proinflammatory markers in healthy young adults.

Objective To study the association between adherence to several a priori-defined healthy food patterns and the risk of hypertension. Design Prospective, multipurpose, dynamic cohort study (recruitment permanently open). We followed up 10 800 men and women (all of them university graduates), who were initially free of hypertension, for a variable period (range 2–6 years, median 4·6 years). During follow-up, 640 participants reported a new medical diagnosis of hypertension. Baseline diet was assessed using a validated 136-item FFQ. Validated information about non-dietary potential confounders was also gathered. We calculated adherence to fifteen different hypothesis-oriented food patterns and assessed the association between each of them and incident hypertension using multivariable Cox models. Setting The SUN (Seguimiento Universidad de Navarra – University of Navarra Follow-up) Project, Spain. Subjects Participants recruited to the SUN cohort before October 2005 were eligible for inclusion; after excluding those with self-reported hypertension or CVD at baseline, or with extreme total energy intake, data of 10 800 were analysed. Results Higher adherence to the DASH (Dietary Approaches to Stop Hypertension) diet (range of the score: 0 to 5) was significantly associated with a lower risk for developing hypertension (P for trend = 0·02). The other food patterns showed no significant association with incident hypertension. Conclusions Our results support a long-term protection of the DASH diet against the incidence of hypertension, but we found no evidence of a similar inverse association with hypertension for any other a priori-defined healthy food pattern.