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Digital, Background & aim Inflammation and oxidative stress are the most probable mechanistic link between obesity and its co-diseases with cancer among them. The aim of this study was to evaluate whether the nutritional ketosis and weight loss induced by a very-low-calorie ketogenic diet (VLCKD) modulates the inflammatory and oxidative stress profile, compared with a standard, balanced hypocaloric diet (LCD) or bariatric surgery (BS) in patients with obesity. Methods The study was performed in 79 patients with overweight or obesity and 32 normal-weight volunteers as the control group. Patients with obesity underwent a weight reduction therapy based on VLCKD, LCD or BS. The quantification of the circulating levels of a multiplexing test of cytokines and carcinogenesis/aging biomarkers, as well as of lipid peroxides and total antioxidant power, was carried out. Results First, we observed that pro-inflammatory cytokines increase, while anti-inflammatory cytokines decrease under excessive body weight. Relevantly, when patients underwent weight loss strategies, it was shown that energy-restricted and surgical strategies of weight loss induced changes in circulating cytokine and lipid peroxides. This effect was more notable in patients following the VLCKD than the LCD or BS and it was observed mainly in the ketosis phase of the intervention. Particularly, IL-11, IL-12, IL-2, INF-γ, INF-β, Pentraxin-3 or MMP1 changed after VLCKD. Whereas, APRIL, TWEAK, osteocalcin and IL-28A increased after BS. Conclusion As far as we know, this is the first study that evaluate the time-course of cytokines and oxidative stress markers after a VLCKD as compared with a standard LCD and BS. The observed results support the immunomodulatory effect of nutritional ketosis induced by a VLCKD synergistically with weight loss as a strategy to improve innate-immunity and to prevent infections and carcinogenesis in patients with obesity., Ciencias Médicas y de la Salud

Non-alcoholic fatty liver disease (NAFLD) development is linked to insulin resistance and influenced by environmental factors, but it also underlined a genetic predisposition. The aim of this research was 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.A 6-month nutritional intervention was conducted in 86 overweight/obese volunteers with NAFLD randomly assigned to 2 energy-restricted diets: the American Heart Association (AHA) diet and the Fatty Liver in Obesity (FLiO) diet. Individuals were genotyped using a predesigned panel of 95 genetic variants. A Genetic Risk Score (GRS) for each diet was computed using statistically relevant SNPs for the change on Fatty Liver Index (FLI) after 6-months of nutritional intervention. Body composition, liver injury and insulin resistance markers, as well as physical activity and dietary intake were also assessed.Under energy restriction, both the AHA and FLiO diets induced similar significant improvements on body composition, insulin resistance markers, hepatic health and dietary and lifestyle outcomes. The calculated score included in the linear mixed regression model was able to predict the change of FLI adjusted by diet, age and sex. This model allowed to personalize the most suitable diet for 72% of the volunteers. Similar models were also able to predict the changes on Triglycerides and Glucose (TyG) Index and retinol-binding protein 4 (RBP4) levels depending on diet.Models integrating genetic screening and insulin resistance markers can be useful for the personalization of NAFLD weight loss treatments.

Non-alcoholic fatty liver disease (NAFLD) is worldwide recognized as the most common cause of chronic liver disease. Current NAFLD clinical management relies on lifestyle change, nevertheless, the importance of the genetic make-up on liver damage and the possible interactions with diet are still poorly understood. The aim of the study was 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. In addition, gene-treatment interactions over the course of the intervention were examined. The SH2B1 genetic variant was genotyped in 86 overweight/obese subjects with NAFLD from the FLiO study (Fatty Liver in Obesity study). Subjects were metabolically evaluated at baseline and at 6-months. Liver assessment included ultrasonography, Magnetic Resonance Imaging, elastography, a lipidomic test (OWL®-test) and specific blood liver biomarkers. Additionally, body composition, general biochemical markers and dietary intake were determined. Both genotypes significantly improved their body composition, general metabolic status and liver health after following an energy-restricted strategy. Liver imaging techniques showed a greater decrease in liver fat content (− 44.3%, p

[Objectives] The number of people aged ≥60 y is increasing worldwide, so establishing a relationship between lifestyle and health-associated factors, such as gut microbiota in an older population, is important. This study aimed to characterize the gut microbiota of a presenior population, and analyze the association between some bacteria and quality of life with the Short Form (SF) 36 questionnaire., [Methods] Participants were adult men and women ages 50 to 80 y (n = 74). In addition to the SF-36 questionnaire, fecal samples were collected in cryotubes, and 16S RNA gene sequencing was performed to characterize microbial features. Participants were classified into two groups according to SF-36 punctuation. Linear and logistic regression models were performed to assess the possible association between any bacterial bowl and SF-36 score. Receiver operating characteristics curves were fitted to define the relative diagnostic strength of different bacterial taxa for the correct determination of quality of life., [Results] A positive relationship was established between SF-36 score and Actinobacteria (P = 0.0310; R = 0.2510) compared with Peptostreptococcaceae (P = 0.0259; R = –0.2589), which increased with decreasing quality of life. Logistic regressions models and receiver operating characteristics curves showed that the relative abundance of Actinobacteria and Peptostreptococcaceae may be useful to predict quality of life in a presenior population (area under the curve: 0.71)., [Conclusions] Quality of life may be associated with the relative abundance of certain bacteria, especially Actinobacteria and Peptostreptococcaceae, which may have a specific effect on certain markers and health care, which is important to improve quality of life in older populations., The authors express their gratitude to the NUTRIPRECISION consortium associated with the project “Strategies for improving the quality of life of presenior and senior populations based on precision nutrition”. The authors gratefully acknowledge the financial support from CDTI through the Programa Estratégico CIEN (IDI-20160734), cofounded by the European Regional Development Fund. The physician (B.E. Martínez de Morentin), dietitians (M. Hernández, N. Hernández), nurses (C. Castejón, S. Pérez), and technicians (V. Ciaurriz, M. Zabala) are thanked for their contribution to the Nutriprecision project. Begoña de Cuevillas appreciates the predoctoral grant received from Congelados de Navarra.

Identification of dietary factors involved in the development and progression of nonalcoholic fatty liver disease (NAFLD) is relevant to the current epidemics of the disease. Dietary amino acids appear to play a key role in the onset and progression of NAFLD. The aim of this study was to analyze potential associations between specific dietary amino acids and variables related to glucose metabolism and hepatic status in adults with overweight/obesity and NAFLD. One hundred and twelve individuals from the Fatty Liver in Obesity (FLiO) study were evaluated. Liver assessment was carried out by ultrasonography, magnetic resonance imaging and analysis of biochemical parameters. Dietary amino acid intake (aromatic amino acids (AAA); branched-chain amino acids (BCAA); sulfur amino acids (SAA)) was estimated by means of a validated 137-item food frequency questionnaire. Higher consumption of these amino acids was associated with worse hepatic health. Multiple adjusted regression models confirmed that dietary AAA, BCAA and SAA were positively associated with liver fat content. AAA and BCAA were positively associated with liver iron concentration. Regarding ferritin levels, a positive association was found with BCAA. Dietary intake of these amino acids was positively correlated with glucose metabolism (glycated hemoglobin, triglyceride and glucose index) although the significance disappeared when potential confounders were included in the model. These findings suggest that the consumption of specific dietary amino acids might negatively impact on liver status and, to a lesser extent on glucose metabolism in subjects with overweight/obesity and NAFLD. A control of specific dietary amino acid composition should be considered in the management of NAFLD and associated insulin resistance. NCT03183193; June 2017.

The Paleolithic diet (PaleoDiet) is an allegedly healthy dietary pattern inspired by the consumption of wild foods and animals assumed to be consumed in the Paleolithic era. Despite gaining popularity in the media, different operational definitions of this Paleolithic nutritional intake have been used in research. Our hypothesis is that specific components used to define the PaleoDiet may modulate the association of this diet with several health outcomes. We comprehensively reviewed currently applied PaleoDiet scores and suggested a new score based on the food composition of current PaleoDiet definitions and the theoretical food content of a staple dietary pattern in the Paleolithic age. In a PubMed search up to December 2019, fourteen different PaleoDiet definitions were found. We observed some common components of the PaleoDiet among these definitions although we also found high heterogeneity in the list of specific foods that should be encouraged or banned within the PaleoDiet. Most studies suggest that the PaleoDiet may have beneficial effects in the prevention of cardiometabolic diseases (type 2 diabetes, overweight/obesity, CVD and hyperlipidaemias) but the level of evidence is still weak because of the limited number of studies with a large sample size, hard outcomes instead of surrogate outcomes and long-term follow-up. Finally, we propose a new PaleoDiet score composed of eleven food items, based on a high consumption of fruits, nuts, vegetables, fish, eggs and unprocessed meats (lean meats); and a minimum content of dairy products, grains and cereals, and legumes and practical absence of processed (or ultra-processed) foods or culinary ingredients.

Resumen Introduccion y objetivos Los beneficios cardiovasculares de la dieta mediterranea se han evaluado bajo supuestos de ingesta total de energia ad libitum (sin restriccion de energia). En el presente trabajo se estudia basalmente la cohorte de un gran ensayo en marcha denominado PREDIMED-Plus y la asociacion entre la adherencia a la dieta mediterranea hipocalorica segun la escala de 17 puntos (MedDiet) de este ensayo con la prevalencia inicial de factores de riesgo cardiovascular (FRCV). Metodos Evaluacion transversal de los participantes de PREDIMED-Plus (6.874 adultos mayores con sobrepeso/obesidad y sindrome metabolico). Se evaluo a los participantes para determinar la prevalencia de 4 FRCV (hipertension, obesidad, diabetes, dislipemia). Se estimaron diferencias de medias y razones de prevalencia para FRCV individuales y agrupados con modelos multivariables. Resultados Una mejor adhesion al patron MedDiet se asocio significativamente con niveles mas bajos de trigliceridos, indice de masa corporal y perimetro abdominal. Comparado con una baja adhesion (≤ 7 puntos en el score de 17 puntos), una mejor adhesion a la MedDiet (11-17 puntos) mostro asociaciones inversas con hipertension (razon de prevalencia = 0,97; IC95%, 0,94-1,00) y obesidad (razon de prevalencia = 0,96; IC95% 0,92-1,00), pero se observaron asociaciones positivas con diabetes (razon de prevalencia = 1,19; IC95% 1,07-1,32). Comparado con el tercil mas bajo de adhesion, las mujeres en el tercil superior mostraron un riesgo menor para la agrupacion de 3 o mas FRCV (razon de prevalencia = 0,91; IC95% 0,83-0,98). Conclusiones Entre participantes con alto riesgo cardiovascular, la mejor adhesion a MedDiet se asocio a mejores perfiles lipidicos y medidas de adiposidad, y entre las mujeres mostro asociaciones inversas significativas con la agregacion de FRCV. Este ensayo se registro en 2014 en el International Standard Randomized Controlled Trial Registry (ISRCTN89898870).

Introduction and objectives The cardiovascular benefits of the Mediterranean diet have usually been assessed under assumptions of ad libitum total energy intake (ie, no energy restriction). In the recently launched PREDIMED-Plus, we conducted exploratory analyses to study the baseline associations between adherence to an energy-restricted Mediterranean diet (MedDiet) and the prevalence of cardiovascular risk factors (CVRF). Methods Cross-sectional assessment of all PREDIMED-Plus participants (6874 older adults with overweight/obesity and metabolic syndrome) at baseline. The participants were assessed by their usual primary care physicians to ascertain the prevalence of 4 CVRF (hypertension, obesity, diabetes, and dyslipidemia). A 17-point PREDIMED-Plus score was used to measure adherence to the MedDiet. Multivariable models were fitted to estimate differences in means and prevalence ratios for individual and clustered CVRF. Results Better adherence to a MedDiet pattern was significantly associated with lower average triglyceride levels, body mass index, and waist circumference. Compared with low adherence (≤ 7 points in the 17-point score), better adherence to the MedDiet (11-17 points) showed inverse associations with hypertension (prevalence ratio = 0.97; 95%CI, 0.94-1.00) and obesity (prevalence ratio = 0.96; 95%CI, 0.92-1.00), but positive associations with diabetes (prevalence ratio = 1.19; 95%CI, 1.07-1.32). Compared with the lowest third of adherence, women in the upper third showed a significantly lower prevalence of the clustering of 3 or more CVRF (prevalence ratio = 0.91; 95%CI, 0.83-0.98). Conclusions Among participants at high cardiovascular risk, better adherence to a MedDiet showed significant inverse associations with CVRF among women, and improved lipid profiles and adiposity measures. This trial was registered in 2014 at the International Standard Randomized Controlled Trial Registry (ISRCTN89898870).

Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS), which is co-funded by the European Regional Development Fund (six coordinated FIS projects leaded by JS-S and JVi, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332, PI20/01802, PI20/00138, PI20/01532, PI20/00456, PI20/00339, PI20/00557, PI20/00886, PI20/01158); the Especial Action Project entitled: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grant to JS-S; the European Research Council (Advanced Research Grant 2014-2019; agreement #340918) granted to MAMG.; the Recercaixa (number 2013ACUP00194) grant to JS-S; grants from the Consejeria de Salud de la Junta de Andalucia (PI0458/2013, PS0358/2016, PI0137/2018); the PROMETEO/2017/017 and the PROMETEO 21/2021 grant from the Generalitat Valenciana; the SEMERGEN grant; the Boosting young talent call grant program for the development of IISPV research projects 2019-2021 (Ref.: 2019/IISPV/03 grant to AD-L); the Societat Catalana d'Endocrinologia i Nutricio (SCEN) Clinical-Research Grant 2019 (IPs: JS-S and AD-L). Collaborative Nutrition and/or Obesity Project for Young Researchers 2019 supported by CIBEROBN entitled: Lifestyle Interventions and Chronic Kidney Disease: Inflammation, Oxidative Stress and Metabolomic Profile (LIKIDI study) grant to AD-L. Jordi Salas-Salvado, gratefully acknowledges the financial support by ICREA under the ICREA Academia programme. M.R.-G., is supported by the Ministry of Education of Spain (FPU17/06488). None of the funding sources took part in the design, collection, analysis, interpretation of the data, or writing the report, or in the decision to submit the manuscript for publication., Purpose To assess the association between three different a priori dietary patterns adherence (17-item energy reduced- Mediterranean Diet (MedDiet), Trichopoulou-MedDiet and Dietary Approach to Stop Hypertension (DASH)), as well as the Protein Diet Score and kidney function decline after one year of follow-up in elderly individuals with overweight/obesity and metabolic syndrome (MetS). Methods We prospectively analyzed 5675 participants (55–75 years) from the PREDIMED-Plus study. At baseline and at one year, we evaluated the creatinine-based estimated glomerular filtration rate (eGFR) and food-frequency questionnairesderived dietary scores. Associations between four categories (decrease/maintenance and tertiles of increase) of each dietary pattern and changes in eGFR (ml/min/1.73m2) or ≥ 10% eGFR decline were assessed by fitting multivariable linear or logistic regression models, as appropriate. Results Participants in the highest tertile of increase in 17-item erMedDiet Score showed higher upward changes in eGFR (β: 1.87 ml/min/1.73m2; 95% CI: 1.00–2.73) and had lower odds of ≥ 10% eGFR decline (OR: 0.62; 95% CI: 0.47–0.82) compared to individuals in the decrease/maintenance category, while Trichopoulou-MedDiet and DASH Scores were not associated with any renal outcomes. Those in the highest tertile of increase in Protein Diet Score had greater downward changes in eGFR (β: − 0.87 ml/min/1.73m2; 95% CI: − 1.73 to − 0.01) and 32% higher odds of eGFR decline (OR: 1.32; 95% CI: 1.00–1.75). Conclusions Among elderly individuals with overweight/obesity and MetS, only higher upward change in the 17-item erMedDiet score adherence was associated with better kidney function after one year. However, increasing Protein Diet Score appeared to have an adverse impact on kidney health. Trial Registration Number: ISRCTN89898870 (Data of registration: 2014)., CRUE-CSIC agreement, Springer Nature, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS), European Commission PI13/00673 PI13/00492 PI13/00272 PI13/01123 PI13/00462 PI13/00233 PI13/02184 PI13/00728 PI13/01090 PI13/01056 PI14/01722 PI14/00636 PI14/00618 PI14/00696 PI14/01206 PI14/01919 PI14/00853 PI14/01374 PI14/00972 PI14/00728, The European Regional Development Fund PI14/01471 PI16/00473 PI16/00662 PI16/01873 PI16/01094 PI16/00501 PI16/00533 PI16/00381 PI16/00366 PI16/01522 PI16/01120 PI17/00764 PI17/01183 PI17/00855 PI17/01347 PI17/00525 PI17/01827 PI17/00532, European Commission PI19/01226 PI19/00781 PI19/01560 PI19/01332 PI20/01802 PI20/00138 PI20/01532 PI20/00456 PI20/00339 PI20/00557 PI20/00886 PI20/01158, Especial Action Project entitled: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grant, European Research Council (ERC), European Commission 340918, Recercaixa grant 2013ACUP00194, Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018, Generalitat Valenciana, European Commission, General Electric PROMETEO/2017/017 PROMETEO 21/2021 SEMERGEN grant, Boosting young talent call grant program for the development of IISPV research projects 2019-2021 2019/IISPV/03, Societat Catalana d'Endocrinologia i Nutricio (SCEN) Clinical-Research Grant 2019, CIBEROBN entitled: Lifestyle Interventions and Chronic Kidney Disease: Inflammation, Oxidative Stress and Metabolomic Profile (LIKIDI study) grant, ICREA, Spanish Government FPU17/06488, European Commission PI17/00215 PI17/01441 PI17/00508 PI17/01732 PI17/00926 PI19/00957 PI19/00386 PI19/00309 PI19/01032 PI19/00576 PI19/00017

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the global population. The pathogenesis of NAFLD is complex, available data reveal that genetics and ascribed interactions with environmental factors may play an important role in the development of this morbid condition. The purpose of this investigation was to assess genetic and non-genetic determinants putatively involved in the onset and progression of NAFLD after a 6-month weight loss nutritional treatment. A group of 86 overweight/obese subjects with NAFLD from the Fatty Liver in Obesity (FLiO) study were enrolled and metabolically evaluated at baseline and after 6 months. A pre-designed panel of 95 genetic variants related to obesity and weight loss was applied and analyzed. Three genetic risk scores (GRS) concerning the improvement on hepatic health evaluated by minimally invasive methods such as the fatty liver index (FLI) (GRSFLI), lipidomic-OWLiver®-test (GRSOWL) and magnetic resonance imaging (MRI) (GRSMRI), were derived by adding the risk alleles genotypes. Body composition, liver injury-related markers and dietary intake were also monitored. Overall, 23 SNPs were independently associated with the change in FLI, 16 SNPs with OWLiver®-test and 8 SNPs with MRI, which were specific for every diagnosis tool. After adjusting for gender, age and other related predictors (insulin resistance, inflammatory biomarkers and dietary intake at baseline) the calculated GRSFLI, GRSOWL and GRSMRI were major contributors of the improvement in hepatic status. Thus, fitted linear regression models showed a variance of 53% (adj. R2 = 0.53) in hepatic functionality (FLI), 16% (adj. R2 = 0.16) in lipidomic metabolism (OWLiver®-test) and 34% (adj. R2 = 0.34) in liver fat content (MRI). These results demonstrate that three different genetic scores can be useful for the personalized management of NAFLD, whose treatment must rely on specific dietary recommendations guided by the measurement of specific genetic biomarkers.

The PREDIMEDPlus trial was supported by the Spanish government's official funding agency for biomedical research, ISCIII, through the Fondo de Investigacion para la Salud (FIS) and cofunded by European Union ERDF/ESF, "A way to make Europe"/"Investing in your future" (five coordinated FIS projects led by JS-S and JVid, including the following: PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/00728, PI14/01722, PI14/00636, PI14/01206, PI14/01919, PI14/01374, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00366, PI17/00764, PI17/01827, PI17/01441, PI17/01732, PI17/00926, PI19/00309, PI19/01032, PI19/00576, PI19/00017, and PI19/00781) , the Special Action Project entitled: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grant to JSS, the European Research Council (Advanced Research Grant 2013-2018, 340918) to MAMG, the Recercaixa Grant to JS-S (2013ACUP00194) , a grant from the Generalitat Valenciana (PROMETEO/2017/017) , a SEMER-GEN grant, and funds from the European Regional Development Fund (CB06/03) . Study resulting from the SLT006/17/00246 grant, funded by the Department of Health of the Generalitat de Catalunya by the call "Accio instrumental de programes de recerca orientats en l'ambit de la recerca i la innovacio en salut". We thank the CERCA Programme/Generalitat de Catalunya for institutional support. This publication has been possible with the support of the Ministerio de Ciencia, Innovacion y Universidades (MICINN) (FPU 17/01925) . Jordi SalasSalvado, senior author of this study, is partially supported by ICREA under the ICREA Academia programme. IP-G receives a grant from the Spanish Ministry of Education, Culture and Sports (FPU 17/01925) . Dr. NB-T is supported by a postdoctoral fellowship (Juan de la Cierva-Formacion, FJC2018-036016-I) . I.M GimenezAlba received an FPU grant from the Ministry of Science, Innovation and Universities (reference FPU 18/01703) . C.B. received a Fernando Tarongi Bauza PhD Grant., Background & aims: The association between drinking water consumption and adiposity has been poorly explored. Therefore, we aimed to analyse the associations between the frequency of drinking water consumption and body weight and waist circumference changes in an elderly Mediterranean cohort. Methods: A total of 1832 elderly participants (aged 55e75 years) with metabolic syndrome from the PREDIMED-Plus study with baseline data on drinking water and other beverages assessed by a validated 32-item Spanish fluid-intake questionnaire and with data on body weight (BW) and waist circumference (WC) at 1-year and 2-year were included in these prospective analyses. Multivariable linear regression models were fitted to assess the b-coefficients and 95% confidence interval (CI) for BWand WC changes in terms of categories of baseline drinking water consumption (tap water and bottled water). The theoretical effect on BWand WC of replacing several beverages with drinking water was assessed using mathematical models. Results: The baseline frequency of drinking water consumptionwas inversely associated with 1-year and 2- year changes in BW. b-coefficients (95%CI) across categories ofwater consumption (, Spanish Government European Commission, European Union ERDF/ESF, "A way to make Europe"/"Investing in your future" PI13/00272 PI13/01123 PI13/00462 PI13/00233 PI13/00728 PI14/01722 PI14/00636 PI14/01206 PI14/01919 PI14/01374 PI16/01873 PI16/01094 PI16/00501 PI16/00533 PI16/00366, Special Action Project entitled: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grant, European Research Council (ERC), European Commission 340918, Recercaixa Grant 2013ACUP00194, Generalitat Valenciana European Commission PROMETEO/2017/017, SEMER-GEN grant European Commission CB06/03, Department of Health of the Generalitat de Catalunya SLT006/17/00246, Ministerio de Ciencia, Innovacion y Universidades (MICINN) FPU 17/01925, ICREA under the ICREA Academia programme, Spanish Ministry of Education, Culture and Sports FPU 17/01925, Juan de la Cierva-Formacion FJC2018-036016-I, Ministry of Science, Innovation and Universities FPU 18/01703, Fernando Tarongi Bauza PhD Grant, The European Union ERDF/ESF, "A way to make Europe"/"Investing in your future" PI17/00764 PI17/01827 PI17/01441 PI17/01732 PI17/00926 PI19/00309 PI19/01032 PI19/00576 PI19/00017 PI19/00781

Introduction: Non-alcoholic fatty liver disease (NAFLD) may progress to steatohepatitis, cirrhosis and complicated hepatocellular carcinoma with defined differential symptoms and manifestations. Objective: To evaluate the fatty liver status by several validated approaches and to compare imaging techniques, lipidomic and routine blood markers with magnetic resonance imaging in adults subjects with non-alcoholic fatty liver disease. Materials and methods: A total of 127 overweight/obese with NAFLD, were parallelly assessed by Magnetic Resonance Imaging (MRI), ultrasonography, transient elastography and a validated metabolomic designed test to diagnose NAFLD in this cross-sectional study. Body composition (DXA), hepatic related biochemical measurements as well as the Fatty Liver Index (FLI) were evaluated. This study was registered as FLiO: Fatty Liver in Obesity study; NCT03183193. Results: The subjects with more severe liver disease were found to have worse metabolic parameters. Positive associations between MRI with inflammatory and insulin biomarkers were found. A linear regression model including ALT, RBP4 and HOMA-IR was able to explain 40.9% of the variability in fat content by MRI. In ROC analyses a combination panel formed of ALT, HOMA-IR and RBP4 followed by ultrasonography, ALT and metabolomic test showed the major predictive ability (77.3%, 74.6%, 74.3% and 71.1%, respectively) for liver fat content. Conclusions: A panel combination including routine blood markers linked to insulin resistance showed highest associations with MRI considered as a gold standard for determining liver fat content. This combination of tests can facilitate the diagnosis of early stages of non-alcoholic liver disease thereby avoiding other invasive and expensive methods., Health Department of the Government of Navarra (61/2015), CIBERobn (Physiopathology of Obesity and Nutrition) and to Fundacio La Marato de TV3 (201630.10).

IntroductionPrevious studies have hypothesized Fibroblast growth factor 21 (FGF-21) as a potential biomarker of the inflammation associated to liver diseases, which is also receiving high attention for its potential application concerning the management of obesity and co-morbidities. This study aimed to analyze the response of FGF-21 after a weight loss intervention and the relationships with other putative inflammatory liver biomarkers.Material and methodsSixty-six obese participants from the RESMENA study were evaluated at baseline and after following a 6-months energy restriction treatment. Anthropometrical, body composition by DXA, routine laboratory measurements, which included transaminases and gamma-glutamyl transferase (GGT) were analyzed by standardized methods. Moreover, FGF-21, M30-fragment (M30) and plasminogen activator inhibitor-1 (PAI-I) were analyzed as recognized liver inflammatory related biomarkers with specific ELISA Kits.ResultsMost measurements related with hepatic damage, inflammation and adiposity status improved at the end of the 6-months nutritional intervention. In addition, ΔFGF-21 shifts evidenced statistical relationships with changes in ΔM30, ΔGGT and ΔPAI. The reduction of M30 showed significant associations with changes in transaminases. Furthermore, PAI-I changes were related with ΔM30 and ΔGGT regardless of weight loss. A linear regression model was set up to assess the influence of ΔPAI-I and ΔM30 on the variability of ΔFGF-21 (23.8%) adjusted by weight loss.ConclusionsThese results evidenced interactions of some liver inflammatory mediators, specifically M30 and PAI-I with FGF-21. Thus, more investigation about FGF-21 is required given that this protein could be a biomarker of the obesity-inflammation-liver process.

Background and aims: Previous studies, mainly focused on quantity rather than variety, have shown beneficial associations between the amount of fruit and vegetable consumed, diet quality and healthy lifestyle. The aim is to evaluate the association between fruit and vegetable consumption, diet quality and lifestyle in an elderly Mediterranean population, considering both variety and the combination of quantity and variety (QV). Methods: A cross-sectional analysis of 6647 participants (51.6% of males) was conducted in the framework of the PREDIMED-Plus study. A variety score was created as the sum of vegetables and/or fruits consumed at least once per month using food frequency questionnaires. Dietary Reference Intakes (EAR and IA values) were used to estimate the prevalence of inadequate intake of dietary fiber and micro nutrients. Logistic regression models were performed to examine the association between fruit and vegetable consumption and not meeting the DRIs, by tertiles of fruit and vegetable variety and QV categories. Results: Participants with higher fruit and vegetable variety score reported a significant higher intake of fiber, vitamins, minerals and flavonoids and were significantly more likely to be physically active and non-smoker. Besides, higher variety in fruit and vegetable consumption was associated with lower prevalence of having an inadequate intake of fiber [(0.13 (0.11-0.16)], two or more [(0.17 (0.14-0.21)], three or more [(0.15 (0.13-0.18)] and four or more [(0.11 (0.10-0.14)] micronutrients in our participants. Higher quantity and variety in fruit and vegetable consumption was associated with lower prevalence of having an inadequate intake of fiber [(0.05 (0.04-0.06)], two or more [(0.08 (0.06-0.10)], three or more [(0.08 (0.06-0.09)] and four or more [(0.06 (0.05-0.07)] micronutrients. Conclusion: Greater variety in fruit and vegetable intake was associated with better nutrient adequacy, diet quality and healthier lifestyle in an elderly Mediterranean population. (c) 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The identification of affordable noninvasive biomarkers for the diagnosis and characterization of nonalcoholic fatty liver disease (NAFLD) is a major challenge for the research community. This study aimed to explore the usefulness of ferritin as a proxy biomarker of NAFLD condition, alone or in combination with other routine biochemical parameters. Subjects with overweight/obesity and ultrasound-confirmed liver steatosis (n = 112) from the Fatty Liver in Obesity (FLiO) study were assessed. The hepatic evaluation considered magnetic resonance imaging, ultrasonography, and credited routine blood liver biomarkers. Anthropometry and body composition, dietary intake (by means of a validated 137-item food frequency questionnaire), and specific biochemical markers were also determined. Serum ferritin levels were analyzed using a chemiluminescent microparticle immunoassay kit. Lower serum ferritin concentrations were associated with general better liver health and nutritional status. The evaluation of ferritin as a surrogate of liver damage by means of quantile regression analyses showed a positive association with alanine aminotransferase (ALT) (&beta, = 19.21, p &le, 0.001), liver fat content (&beta, = 8.70, p = 0.008), and hepatic iron (&beta, = 3.76, 0.001), after adjusting for potential confounders. In receiver operating characteristic (ROC) analyses, the panel combination of blood ferritin, glucose, and ALT showed the best prediction for liver fat mass (area under the curve (AUC) 0.82). A combination of ferritin and ALT showed the higher predictive ability for estimating liver iron content (AUC 0.73). This investigation demonstrated the association of serum ferritin with liver health as well as with glucose and lipid metabolism markers in subjects with NAFLD. Current findings led to the identification of ferritin as a potential noninvasive predictive biomarker of NAFLD, whose surrogate value increased when combined with other routine biochemical measurements (glucose/ALT).

[Background and aims]: The aim of this study was to ascertain the association between the consumption of different categories of edible olive oils (virgin olive oils and olive oil) and olive pomace oil and ankle-brachial pressure index (ABI) in participants in the PREDIMED-Plus study, a trial of lifestyle modification for weight and cardiovascular event reduction in individuals with overweight/obesity harboring the metabolic syndrome., [Methods]: We performed a cross-sectional analysis of the PREDIMED-Plus trial. Consumption of any category of olive oil and olive pomace oil was assessed through a validated food-frequency questionnaire. Multivariable linear regression models were fitted to assess associations between olive oil consumption and ABI. Additionally, ABI ≤1 was considered as the outcome in logistic models with different categories of olive oil and olive pomace oil as exposure., [Results]: Among 4330 participants, the highest quintile of total olive oil consumption (sum of all categories of olive oil and olive pomace oil) was associated with higher mean values of ABI (beta coefficient: 0.014, 95% confidence interval [CI]: 0.002, 0.027) (p for trend = 0.010). Logistic models comparing the consumption of different categories of olive oils, olive pomace oil and ABI ≤1 values revealed an inverse association between virgin olive oils consumption and the likelihood of a low ABI (odds ratio [OR] 0.73, 95% CI [0.56, 0.97]), while consumption of olive pomace oil was positively associated with a low ABI (OR 1.22 95% CI [1.00, 1.48])., [Conclusions]: In a Mediterranean population at high cardiovascular risk, total olive oil consumption was associated with a higher mean ABI. These results suggest that olive oil consumption may be beneficial for peripheral artery disease prevention, but longitudinal studies are needed., The authors especially thank the PREDIMED-Plus participants for their enthusiastic collaboration, the PREDIMED-Plus personnel for outstanding support, and the personnel of all associated primary care centres for their exceptional effort. CIBEROBN, CIBERESP and CIBERDEM are initiatives of Instituto de Salud Carlos III, Spain.

BackgroundMetabolic syndrome (MetS) comprises several clinical and metabolic risk factors that increase the risk to develop cardiovascular disease and other comorbidities. Meanwhile, ageing and biological differences between men and women play an important role in body fat distribution and health status. The current study aimed to evaluate the association of visceral adipose tissue (VAT) and the triglyceride and glucose index (TyG) with metabolic and liver risk factors among subjects diagnosed with MetS with emphasis on differences attributable to sex.MethodsA cross-sectional study was performed including 326 individuals with MetS (54–75 years) from the PREDIMED-Plus study. Liver markers, visceral fat (VAT) and the triglyceride glucose index (TyG) were assessed. Participants were stratified according to VAT and TyG tertiles. Receiver operating characteristic (ROC) curve was used to analyze the efficiency of TyG for VAT.ResultsSubjects with greater visceral fat depots showed worse lipid profile, higher HOMA-R, TyG, ALT, fibroblast growth factor-21 (FGF-21), fatty liver index (FLI) and hepatic steatosis index (HSI) compared to participants in the 1st tertile. The multi-adjusted linear regression analyses indicated that individuals in the third tertile of TyG (> 9.1–10.7 units) had a positive association with HOMA-IR (β = 3.07 [95% CI, 2.28–3.86]; p-trend

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 = 0.001, and Fatty Liver Index (FLI) p = 0.032. Higher protein consumption (p = 0.028), less mono-unsaturated fatty acid and fiber intake (p = 0.045 and p = 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% vs. 44.4%, p = 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.

Background Omega-3 polyunsaturated fatty acids (PUFAs) have been suggested as important biomolecules in the management of nonalcoholic fatty liver disease (NAFLD). Objective This study aimed to evaluate the effect of 6-month weight loss diets on erythrocyte membrane omega-3 PUFA composition of NAFLD adults, and to evaluate the potential relationship between erythrocyte membrane omega-3 PUFAs and hepatic health markers. Methods In this secondary analysis of the Fatty Liver in Obesity study, erythrocyte membranes were analyzed by gas chromatography in 54 subjects with liver steatosis detected by ultrasonography who achieved a weight loss >5% after the follow-up. Baseline and 6-month evaluation included hepatic acoustic radiation force impulse elastography and magnetic resonance imaging, anthropometry, body composition, and biochemical determinations. Results After the follow-up, α-linolenic acid (ALA) proportion significantly increased in erythrocyte membranes, whereas eicosapentaenoic acid (EPA) showed no statistical difference and docosapentaenoic acid decreased. Both the changes in erythrocyte membrane ALA and EPA were positively associated with dietary ALA. Regression analyses evidenced that the changes in erythrocyte membrane ALA and EPA were inversely associated with the changes in liver stiffness and liver iron content, respectively. Conclusion The adherence to weight loss strategies for 6 months led to changes in erythrocyte membrane omega-3 PUFA composition, which in turn were associated with changes in hepatic markers, suggesting that these fatty acids accompany the improvements in the liver during a dietary treatment. These findings show that beyond weight loss, the composition of the diet has an important role in the management of NAFLD.

Identification of dietary factors involved in the development and progression of nonalcoholic fatty liver disease (NAFLD) is relevant to the current epidemics of the disease. Dietary amino acids appear to play a key role in the onset and progression of NAFLD. The aim of this study was to analyze potential associations between specific dietary amino acids and variables related to glucose metabolism and hepatic status in adults with overweight/obesity and NAFLD.One hundred and twelve individuals from the Fatty Liver in Obesity (FLiO) study were evaluated. Liver assessment was carried out by ultrasonography, magnetic resonance imaging and analysis of biochemical parameters. Dietary amino acid intake (aromatic amino acids (AAA); branched-chain amino acids (BCAA); sulfur amino acids (SAA)) was estimated by means of a validated 137-item food frequency questionnaire.Higher consumption of these amino acids was associated with worse hepatic health. Multiple adjusted regression models confirmed that dietary AAA, BCAA and SAA were positively associated with liver fat content. AAA and BCAA were positively associated with liver iron concentration. Regarding ferritin levels, a positive association was found with BCAA. Dietary intake of these amino acids was positively correlated with glucose metabolism (glycated hemoglobin, triglyceride and glucose index) although the significance disappeared when potential confounders were included in the model.These findings suggest that the consumption of specific dietary amino acids might negatively impact on liver status and, to a lesser extent on glucose metabolism in subjects with overweight/obesity and NAFLD. A control of specific dietary amino acid composition should be considered in the management of NAFLD and associated insulin resistance. NCT03183193; June 2017.

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 = 0.001; and Fatty Liver Index (FLI) p = 0.032. Higher protein consumption (p = 0.028), less mono-unsaturated fatty acid and fiber intake (p = 0.045 and p = 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% vs. 44.4%; p = 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.

Processed and ultra-processed foods (UPF) consumption has been associated with development of noncommunicable chronic diseases (NCD). This systematic review aims to summarise and discuss evidence of the relationship between food consumption according to degree of food processing and cardiometabolic risk. Data search was conducted in databases as PubMed, Bireme and Science Direct until July 2018. Studies have shown a positive association of UPF consumption with excess body weight, hypertension, dyslipidemia and metabolic syndrome features. However, disparities found in the studies analysed regarding dietary assessment, confounding factors and differences in food classifications makes comparisons between studies difficult. In conclusion, current evidences indicate the need to monitor UPF intake in global population. However, more studies are necessary to interpret better these associations with similar methodologies used in the studies. As well as longitudinal analyses can help to improve comparisons between outcomes and establish cause-effect relationship between UPF intake and cardiometabolic risk.

Background & aims: Few studies have compared micronutrient intake and fulfilment of average requirements (EAR) in non-diabetic, pre-diabetic and diabetic adults at high cardiovascular risk. We assessed these variables in a large sample of participants in the PREDIMED-PLUS randomized trial of primary cardiovascular prevention with diet and physical activity. Design: Baseline assessment of nutritional adequacy in n = 5792 men and women, aged 55-75 years, with overweight/obesity and some metabolic syndrome features. Methods: Participants were categorised as non-diabetic (n = 2390), pre-diabetic (n = 1322) or diabetic (n = 2080) by standard criteria. Food and nutrient intake were assessed using a validated food frequency questionnaire. Micronutrients examined were vitamins B1, B2, B3, B6, B12, A, C, D, E and folic acid; Ca, K, P, Mg, Fe, Se, Cr, Zn, and iodine. The proportion of micronutrient inadequacy was evaluated using the EAR or adequate intake (AI) cut-offs. Diet quality was also determined using a 17-item energy-restricted Mediterranean diet (MedDiet) questionnaire. Results: Compared to non-diabetic participants, those with pre-diabetes had lower intakes of total carbohydrates (CHO) and higher intakes of total fat and saturated fatty acids (SFA) and were more likely to be below EAR for folic, while diabetic participants had lower intakes of total CHO and higher intakes of protein, total fat, monounsaturated fatty acids, SFA and cholesterol and were less likely to be below EAR for vitamins B2, and B6, Ca, Zn and iodine. Diabetic participants disclosed higher adherence to the MedDiet than the other two groups. Conclusions: Older Mediterranean individuals with metabolic syndrome and diabetes had better nutrient adequacy and adherence to the MedDiet than those with pre-diabetes or no diabetes. (C) 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Obesity rates have experimented a large increase worldwide with a greatly impact on the global population. Low-grade chronic inflammation associated with obesity perpetuates the disease and contributes to the development of related metabolic complications including insulin resistance or cardiovascular disease. Dietary patterns are associated with the incidence of obesity. In fact, several investigations have claimed that adherence to the traditional Mediterranean diet (MD) pattern is negatively associated with the prevalence of overweight/obesity. On the other hand the dietary inflammatory index (DII) has emerged as a potential tool to quantify the inflammatory potential of diet. Thus a number of studies presented in this chapter show that the traditional MD, which is associated with a lower DII, decreases the risk of developing adiposity, contributing to the prevention/treatment of obesity and other inflammatory-related comorbidities. However, the relationships between MD, DII, and adiposity should be further investigated to better understand the molecular interactions that positively impact on noncommunicable diseases.

IntroductionDietary components are contributing factors in the development of Nonalcoholic fatty liver disease (NAFLD). The glycaemic index (GI), glycaemic load (GL) and total antioxidant capacity (TAC) have been considered potential dietary tools influencing diet–disease relationships. The aim of this study was to evaluate associations of the dietary GI, GL, TAC and insulin resistance (IR) condition with hepatic fat in NAFLD adults.Material and methods: 112 overweight/obese adults with NAFLD (age: 50.8 ± 9 years old) were included in the trial. Dietary intake was assessed by a validated 137-item food frequency questionnaire (FFQ). Anthropometric, glycemic and lipid profiles, fatty liver quantification by magnetic resonance imaging (MRI) and IR measured by the Homeostatic Model Assessment of IR (HOMA-IR) were assessed at baseline. This study was registered as FLiO: Fatty Liver in Obesity study; NCT03183193.Results: The median of liver fat content by MRI was 6.4 (3.8–10.9) in the recruited population. Participants with higher liver fat content showed significantly increased values of glucose, insulin, HbA1c and HOMA-IR than those with lower liver fat content (p < 0.05). Correlation analyses revealed relevant positive associations of hepatic fat with GI (r = 0.17; p = 0.077) and GL (r = 0.19; p = 0.047). Also, a negative association between liver fat content and TAC (r = -0.22; p = 0.023) was found. Linear regression analyses were used to examine the associations of hepatic fat and dietary quality indicators as well as IR adjusted for potential confounders (sex, age and physical activity). The final models showed that HOMA-IR, GI, GL and TAC were able to explain between 22.4 and 22.8 % (p < 0.001) of the variability of liver fat content.DiscussionThe pathophysiology of NAFLD is thought to be associated with dietary determinants that contribute to metabolic dysregulation such as IR, ectopic liver fat deposition and hepatic damage. In accordance with other authors, we suggest that monitoring GI, GL and TAC may be useful approaches for the dietary treatment of NAFLD since they are related to hepatic fat. Additionally, it is important to highlight the essential role of IR in NAFLD as a key mediator in the development of NAFLD. Certainly, findings of the present study revealed a significant association of hepatic fat accumulation and IR.In summary, GI, GL and TAC are potential markers of diet quality, with an impact on susceptible population at hepatic risk.

IntroductionNon-alcoholic fatty liver disease (NAFLD) is a chronic liver condition, whose prevalence increases in parallel with obesity, diabetes and metabolic syndrome (MetS) rates. The aim of the study was to investigate the relationships between the triglyceride glucose-body mass index (TyG-BMI) with lifestyle, dietary variables, and metabolic risk factors linked to NAFLD in subjects diagnosed with MetS.Materials and methodsA baseline cross-sectional study on 331 participants (aged 65.8 ± 5.1 years) recruited in Navarra was conducted. Subjects were stratified by tertiles of the TyG-BMI index. Dietetic, Mediterranean diet adherence (MedDiet-17 points) and physical activity data were assessed through validated questionnaires. Sociodemographic, lifestyle, anthropometric and biochemical parameters were also recoreded. The Cockcroft-Gault equation was performed to estimate clearance of creatinine. For comparisons between TyG-BMI tertiles and several variables, ANCOVA and chi-square test analyses were performed.ResultsSubjects in T3 of TyG-BMI index were more likely to have diabetes (50.9%). Interestingly, physical activity decreases across tertiles (p = 0.030). There were no differences between tertiles in energy intake and MedDiet adherence. However, total meat consumption is highest in T3. ANCOVA test after adjustment for potential confounders revealed that participants in T3 showed more several clinical and metabolic alterations. Moreover, ALT (p = 0.002) and GGT (p = 0.047) levels increased and mean corpuscular volume decreased across tertiles of the TyG-BMI index.DiscussionObesity, MetS and insulin resistance (IR) play a key role in the development of NAFLD promoting lipotoxicity and overproduction of proinflammatory mediators. This state induces hepatic steatosis and liver injury. Some studies suggest TyG-BMI index as a surrogate marker of IR and risk to NAFLD(1). In our study, patients in the highest TyG-BMI tertile showed more adverse cardio-metabolic profile, lower physical activity and higher total meat intake. In summary, the TyG-BMI index could be a simple and reliable marker to characterize the risk of NAFLD among individuals diagnosed with MetS.

The authors especially thank the PREDIMED-Plus participants for their enthusiastic collaboration, the PREDIMED-Plus personnel for outstanding support, and the personnel of all associated primary care centres for their exceptional effort. CIBEROBN, CIBERESP and CIBERDEM are initiatives of Instituto de Salud Carlos III, Spain. We thank the PREDIMED-Plus Biobank Network, part of the National Biobank Platform of Instituto de Salud Carlos III for storing and managing biological samples., Healthy lifestyle factors, such as physical activity (PA) and Mediterranean diet (MD), decrease the likelihood of developing metabolic syndrome (MetS). The aim of this study was to report main lifestyle components and related factors according to the MetS severity. Cross-sectional analysis was done of baseline lifestyle factors from 5739 participants with overweight/obesity and MetS features (aged 55–75 years) included in the PREDIMED-PLUS primary cardiovascular prevention randomized trial. Participants were categorized in tertiles according to a validated MetS severity score (MetSSS). Anthropometrics, visceral adiposity index, dietary nutrient intake, biochemical marker levels, as well as a Dietary Inflammatory Index and depression symptoms (Beck Depression Inventory-II) were measured. Diet quality was assessed using a 17-item energy-restricted MD questionnaire. Duration and intensity of PA was self-reported using the Minnesota-REGICOR Short Physical Activity Questionnaire. Sedentary behaviours were measured using the Spanish version of the Nurses’ Health Study questionnaire. The 30 s chair stand test was also assessed. Participants with highest MetSSS showed higher values of cardiovascular risk factors (except for total cholesterol and LDL cholesterol), depression risk, sedentary and TV viewing time, and lower moderate and vigorous leisure-time physical activity (LTPA). Highest MetSSS participants tended to a pro-inflammatory dietary pattern and tended to lower MD adherence. In addition, they showed lower carbohydrate and nut intake and higher intake of protein, saturated and trans fatty acids, cholesterol, iodine, sodium, red and processed meat products, other oils different from olive oil and spirit alcoholic drinks. The highest MetS severity score was associated with lower moderate and vigorous LTPA and higher sedentary time and depression risk, as they tended to a pro-inflammatory dietary pattern and lower MD adherence., The PREDIMED-Plus trial was supported by the official funding agency for biomedical research of the Spanish government, ISCIII, through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund [five coordinated FIS projects led by Jordi Salas-Salvadó and Josep Vidal, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, and PI19/01332], the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to Jordi Salas-Salvadó, the European Research Council (Advanced Research Grant 2014–2019, 340918) to Dr. Miguel A. Martínez-González, the Recercaixa Grant to Jordi Salas-Salvadó (2013ACUP00194), Grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, and PI0137/2018), a Grant from the Generalitat Valenciana (PROMETEO/2017/017), a SEMERGEN Grant, EU-COST Action CA16112, a Grant of support to research groups no. 35/2011 from the Balearic Islands Government, Grants from Balearic Islands Health Research Institute IDISBA [FOLIUM, PRIMUS, SYNERGIA, and LIBERI], funds from the European Regional Development Fund (CIBEROBN CB06/03 and CB12/03) and from the European Commission (EAT2BENICE_H2020_SFS2016). Fundació La Marató TV3 (projects no. PI044003 and 201630.10). Laura Gallardo-Alfaro and Catalina M. Mascaró received FPU PhD Grants from the Spanish Ministry of Education. The funding sponsors had no role in the design of the study, in the collection, analyses, or interpretation of the data; in the writing of the manuscript, and in the decision to publish the results.

Introduction:Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in Western countries and is strongly associated with obesity and insulin resistance-related comorbidities. Moreover, there is some evidence of a relationship between NAFLD and depression. The aim of this study was to compare the effect of two personalized energy-restricted diets on liver fat and depressive symptoms in overweight or obese subjects with NAFLD after a 6-month follow-up.Materials and methods:Ninety-eight overweight or obese adults with NAFLD were enrolled and randomized to follow one of two different personalized energy-restricted diets (American Heart Association vs. FLiO diet) accompanied by healthy lifestyle advice. Study registered as FLiO: Fatty Liver in Obesity; NCT03183193. Anthropometry, body composition, biochemical features and liver status were assessed at baseline and after a 6-month follow-up. Liver fat was evaluated by Magnetic Resonance Imaging and depressive symptoms using the Beck's Depression Inventory-II (BDI-II).Results:Participants of both groups showed significant reductions in body weight, total fat mass, glucose, insulin and alanine aminotransferase (p < 0.001 for all these parameters in both groups). A significant decrease in liver fat (p < 0.001 in both groups) and depressive symptoms (p < 0.01 in both groups) was observed after the follow-up. The effects of the intervention in the evaluated variables did not differ when both diets were compared. Consequently, the two groups were considered together as one sample for the further analyses. Correlation analyses evidenced a positive association between the decrease in depressive symptoms and the reduction in body weight (r = 0.241; p = 0.044) and liver fat (r = 0.251; p = 0.046).Discussion:Previous studies have reported that the prevalence of depression in patients with chronic liver disease (including NAFLD) is higher than in the general population and that major depressive disorder is associated with more severe hepatic steatosis and with worse outcomes in the treatment of NAFLD subjects. In our study, both healthy personalized energy-restricted diets were able to improve metabolic parameters, liver fat content and depressive symptoms in overweight and obese participants with NAFLD. To our knowledge, this is the first study to report an association between the changes in depressive symptoms and the decrease in liver fat after a dietary randomized controlled trial. Further investigation is needed to clarify the relationship between depression and the development and treatment of NAFLD.

The aim of the present investigation was to identify putative miRNAs involved in the response to weight loss. Reverse-transcribed RNA isolated from white blood cells (WBCs) of a subpopulation from the Reduction of the Metabolic Syndrome in Navarra-Spain (RESMENA-S) study (low-responders (LR) and high-responders (HR)) was hybridized in a gene expression microarray. Moreover, miRNAs were sequenced by miRNA-Seq. It was found that miR-548q and miR-1185-1 were overexpressed in HR, both in the microarray and in the miRNA-Seq. A bioinformatic prediction of putative target genes of the selected miRNAs found that GSK3B, a putative target for miR-548q and miR-1185-1, was downregulated in HR. Particular 3′-UTR binding regions of GSK3B were cloned downstream of the firefly luciferase gene. HEK-293T cells were co-transfected with either 0.25 μg of empty pmiR-GLO or pmiR-GLO-548q-3′-UTR/pmiR-GLO-1185-1-3′-UTR, and 7.5 pmol of miR-548q/miR-1185-1 mimics, demonstrating that miR-1185-1 bound to the 3′-UTR region of GSK3B. THP-1 cells were transfected with either 20/40 nM of miR-548q/miR-1185-1 mimics, evidencing that miR-1185-1inhibited the expression of the gene when transfected at doses of 20/40 nM, whereas miR-548q inhibited GSK3B expression at a dose of 40 nM. As a conclusion, miR-548q and miR-1185-1 levels in WBCs are biomarkers of response to weight-loss diets and could be involved in the regulation of the proinflammatory gene GSK3B.