Dietary intake of Perfluorooctanesulfonic acid (PFOS) and glucose homeostasis parameters in a non-diabetic senior population.

BACKGROUND: Endocrine disruptors (EDs) have emerged as potential contributors to the development of type-2 diabetes. Perfluorooctane sulfonate (PFOS), is one of these EDs linked with chronic diseases and gathered attention due to its widespread in food. OBJECTIVE: To assess at baseline and after 1-year of follow-up associations between estimated dietary intake (DI) of PFOS, and glucose homeostasis parameters and body-mass-index (BMI) in a senior population of 4600 non-diabetic participants from the PREDIMED-plus study. METHODS: Multivariable linear regression models were conducted to assess associations between baseline PFOS-DI at lower bound (LB) and upper bound (UB) established by the EFSA, glucose homeostasis parameters and BMI. RESULTS: Compared to those in the lowest tertile, participants in the highest tertile of baseline PFOS-DI in LB and UB showed higher levels of HbA1c [ß-coefficient(CI)] [0.01 %(0.002 to 0.026), and [0.06 mg/dL(0.026 to 0.087), both p-trend ≤ 0.001], and fasting plasma glucose in the LB PFOS-DI [1.05 mg/dL(0.050 to 2.046),p-trend = 0.022]. Prospectively, a positive association between LB of PFOS-DI and BMI [0.06 kg/m2(0.014 to 0.106) per 1-SD increment of energy-adjusted PFOS-DI was shown. Participants in the top tertile showed an increase in HOMA-IR [0.06(0.016 to 0.097), p-trend = 0.005] compared to participants in the reference tertile after 1-year of follow-up. DISCUSSION: This is the first study to explore the association between DI of PFOS and glucose homeostasis. In this study, a high baseline DI of PFOS was associated with a higher levels of fasting plasma glucose and HbA1c and with an increase in HOMA-IR and BMI after 1-year of follow-up.

Priorización de políticas alimentarias en España mediante el Índice Food-EPI de entornos alimentarios saludables: panel de expertos / Prioritization of food policies in Spain through the Food-EPI Index of healthy eating environments: panel of experts

Fundamentos: La conducta alimentaria de los individuos y las influencias ejercidas desde el entorno alimentario es un elementoclave para promover y facilitar el acceso a alimentos saludables. Sin embargo, el conocimiento sobre la implementación de políticassobre entornos alimentarios saludables en España es escaso. El objetivo de este trabajo fue identificar y evaluar el nivel de implementación de políticas alimentarias en España, así como priorizar acciones necesarias para crear entornos alimentarios saludables,con la ayuda por un panel de personas expertas. Métodos: Se creó un panel de personas del mundo académico y la Administración expertas en salud pública, nutrición, políticasalimentarias o de salud, que evaluaron el nivel de implementación de políticas alimentarias en España durante 2018-2020, identificando y priorizando acciones concretas, utilizando elÍndice de Políticas Ambientales de Alimentos de Entornos Alimentarios Saludables(Food-EPI). Se consideraron seis dominios para entornos alimentarios y seis dominios de infraestructura alimentaria. La confiabilidadentre evaluadores se midió utilizandoAgreeStat 2015.6.2 a través de Gwet AC2. Se utilizó la calificación media de los indicadores. Seaplicó el método Delphi.Resultados: Las acciones políticas necesarias en alimentación saludable en España se consideraron bajas (58%) en com-posición, etiquetado, promoción y precios de los alimentos, y muy bajas (25%) en comercio minorista de alimentos. Las accionesprioritarias necesarias de apoyo a las infraestructuras alimentarias saludables se consideraron de importancia media (52%) paraliderazgo y monitorización, y de importancia baja (48%) en gobernanza, financiación y plataformas.Conclusiones: España muestra un gran potencial para crear entornos alimentarios saludables, con una necesidad baja o muy bajade políticas de implementación de entornos alimentarios saludables.(AU)

Background: The eating behaviour of individuals and the influences exerted from the food environment is a key element to promote and facilitate access to healthy foods. However, knowledge about the implementation of policies on healthy food environmentsin Spain is scarce. The aim of this paper was to identify and assess the level of implementation of environmental food policies anddetermine and prioritize actions necessary to create healthy food environments in Spain, helped by a panel of experts. Methods: A panel of experts from the University and the government administration specialized in public health, nutrition, food, orhealth policies was created and invited to participate, asking them to evaluate the level of implementation of food policies in Spain during2018-2020, holding workshops to identify and prioritize concrete actions, using theHealthy Food Environmental Policy Index (Food-EPI).Six key policy domains of food environments, and 6 domains of food infrastructure were considered. Interrater reliability was measuredusingAgreeStat 2015.6.2 through Gwet AC2. The mean rating of the indicators was used. Data analysis was a three-step process byapplication of the Delphi method. Results: The necessary political actions in healthy eating in Spain were considered low (58%) in food composition, labelling, promo-tion, and prices, and very low (25%) in food retail trade. The priority actions needed to support healthy food infrastructures were considered of medium importance (52%) for leadership and monitoring, and of low importance (48%) in governance, financing, and platforms.Conclusions: Spain shows great potential to create healthy food environments, with a low or very low need for policies toimplement healthy food environments, and medium or low support for healthy food infrastructures.(AU)

Leisure-time physical activity at moderate and high intensity is associated with parameters of body composition, muscle strength and sarcopenia in aged adults with obesity and metabolic syndrome from the PREDIMED-Plus study.

AIMS: We aimed to examine the associations of leisure-time physical activity (PA) and sedentary behavior (SB) with the prevalence of sarcopenia, body composition and muscle strength among older adults having overweight/obesity and metabolic syndrome, from the PREDIMED-Plus trial. METHODS: Cross-sectional baseline analysis including 1539 men and women (65 ± 5 y). Sarcopenia was defined as low muscle mass (according to FNIH cut-offs) plus low muscle strength (lowest sex-specific tertile for 30-s chair-stand test). We applied multivariable-adjusted Cox regression with robust variance and constant time (given the cross-sectional design) for the associations of self-reported leisure-time PA and SB with sarcopenia; and multivariable-linear regression for the associations with dual-energy X-ray absorptiometry (DXA)-derived bone mass, fat mass, lean mass and lower-limb muscle strength. RESULTS: Inverse associations were observed between sarcopenia and each hourly increment in total [prevalence ratio 0.81 (95% confidence interval, 0.70, 0.93)], moderate [0.80 (0.66, 0.97)], vigorous [0.51 (0.32, 0.84)], and moderate-vigorous PA (MVPA) [0.74 (0.62, 0.89)]. Incrementing 1-h/day total-PA and MVPA was inversely associated with body-mass-index, waist circumference (WC), fat mass, and positively associated with bone mass and lower-limb muscle strength (all P <.05). One h/day increase in total SB, screen-based SB and TV-viewing was positively associated with body-mass-index, WC and fat mass. Light-PA was not significantly associated with any outcome. CONCLUSIONS: Total-PA and PA at moderate and high intensities may protect against the prevalence of sarcopenia, have a beneficial role on body composition and prevent loss of muscle strength. SB, particularly TV-viewing, may have detrimental effects on body composition in older adults at high cardiovascular risk.

Association of Methylation Signatures at Hepatocellular Carcinoma Pathway Genes with Adiposity and Insulin Resistance Phenotypes.

Obesity and type 2 diabetes mellitus are independent risk factors for the onset and progression of hepatocellular carcinoma (HCC). This study aimed to analyze the association of DNA methylation signatures at HCC pathway genes with obesity and related metabolic disturbances. A population of 474 adults within the Methyl Epigenome Network Association (MENA) project was included. DNA methylation levels were measured in white blood cells by microarray. The identification and discrimination of HCC pathway genes were performed using KEGG and PathDIP databases. Anthropometry measurements, the blood metabolic profile, and clinical data were analyzed. The methylation patterns of 20 CpG sites at HCC pathway genes strongly correlated with BMI (FDR <0.0001). These genes encompassed GADD45A, MTOR, FRAT2, E2F3, WNT7B, FRAT1, LRP5, DPF3, GSTA2, APC, MYC, WNT10B, ARID1B, AKT1, GSTA1, WNT5A, CDK4, GAB1, TCF7, which statistically contributed to the regulation of the HCC pathway (P = 2.10e-07). The main biological process where these genes were implicated included uncontrolled cell proliferation, DNA damage, increased survival, and altered oncogenic expression. Interestingly, 9 out of 20 BMI-associated CpGs also correlated with waist circumference and HOMA-IR index. In conclusion, pathway analysis revealed potential associations of DNA methylation signatures at HCC pathway genes with adiposity and insulin resistance phenotypes.

A Randomized, Double-Blind, Placebo-Controlled Study of Gelesis100: A Novel Nonsystemic Oral Hydrogel for Weight Loss.

OBJECTIVE: This study aims to assess the efficacy and safety of Gelesis100, a novel, nonsystemic, superabsorbent hydrogel to treat overweight or obesity. METHODS: The Gelesis Loss Of Weight (GLOW) study was a 24-week, multicenter, randomized, double-blind, placebo-controlled study in patients with BMI ≥  27 and ≤ 40 kg/m2 and fasting plasma glucose ≥ 90 and ≤ 145 mg/dL. The co-primary end points were placebo-adjusted weight loss (superiority and 3% margin super-superiority) and at least 35% of patients in the Gelesis100 group achieving ≥ 5% weight loss. RESULTS: Gelesis100 treatment caused greater weight loss over placebo (6.4% vs. 4.4%, P = 0.0007), achieving 2.1% superiority but not 3% super-superiority. Importantly, 59% of Gelesis100-treated patients achieved weight loss of ≥ 5%, and 27% achieved ≥ 10% versus 42% and 15% in the placebo group, respectively. Gelesis100-treated patients had twice the odds of achieving ≥ 5% and ≥ 10% weight loss versus placebo (adjusted OR: 2.0, P = 0.0008; OR: 2.1, P = 0.0107, respectively), with 5% responders having a mean weight loss of 10.2%. Patients with prediabetes or drug-naive type 2 diabetes had six times the odds of achieving ≥ 10% weight loss. Gelesis100 treatment had no apparent increased safety risks. CONCLUSIONS: Gelesis100 is a promising new nonsystemic therapy for overweight and obesity with a highly desirable safety and tolerability profile.

Effectiveness of the physical activity intervention program in the PREDIMED-Plus study: a randomized controlled trial.

BACKGROUND: The development and implementation of effective physical activity (PA) intervention programs is challenging, particularly in older adults. After the first year of the intervention program used in the ongoing PREvención con DIeta MEDiterránea (PREDIMED)-Plus trial, we assessed the initial effectiveness of the PA component. METHODS: PREDIMED-Plus is an ongoing randomized clinical trial including 6874 participants randomized to an intensive weight-loss lifestyle intervention based on an energy-restricted Mediterranean diet (MedDiet), physical activity promotion and behavioral support and to a control group using MedDiet recommendations but without calorie restriction or PA advice. Body mass index (BMI) and waist circumference (WC) are measured by standard clinical protocols. Duration and intensity of PA is self-reported using the validated REGICOR Short Physical Activity Questionnaire. The primary endpoint of the PREDIMED-Plus trial is a combined cardiovascular outcome: myocardial infarction (acute coronary syndromes with positive troponin test), stroke, or cardiovascular mortality. The present study involved secondary analysis of PA data (n = 6059; mean age 65 ± 4.9 years) with one-year changes in total, light, and moderate-to-vigorous PA within and between intervention groups as the outcome. Generalized estimating equation models were fitted to evaluate time trends of PA, BMI, and WC within groups and differences between intervention and control groups. RESULTS: After 12 months, average daily MVPA increased by 27.2 (95%CI 5.7;48.7) METs-min/day and 123.1 (95%CI 109.7-136.6) METs-min/day in the control and intervention groups, respectively. Total-PA, light-PA, and MVPA increased significantly (p < 0.01) in both groups. A significant (p < 0.001) time*intervention group interaction was found for Total-PA and MVPA, meaning the PA trajectory over time differed between the intervention and control groups. Age, sex, education level, and BMI did not moderate the effectiveness of the PA intervention. BMI and WC decreased significantly with increasing MVPA, compared with participants who reported no changes in MVPA. CONCLUSION: After one year of follow-up, the PREDIMED-Plus PA intervention has been effective in increasing daily PA in older adults. TRIAL REGISTRATION: Retrospectively registered at the International Standard Randomized Controlled Trial ( http://www.isrctn.com/ISRCTN89898870 ), registration date: 24 July 2014.

Influencia multisensorial sobre la conducta alimentaria: ingesta hedónica / Multisensory influence on eating behavior: Hedonic consumption

Las investigaciones sobre obesidad se centran fundamentalmente en buscar estrategias de prevención y tratamientos encaminados a los cambios de hábitos de estilos de vida. Sin embargo, con nuevas investigaciones, empieza a asumirse que el comportamiento alimentario es una conducta regulada no solo por mecanismos homeostáticos, sino que también es necesario valorar la vía hedónica que regula los procesos de apetito y saciedad. Los factores cognitivos, emocionales, sociales, económicos y culturales y las propiedades organolépticas de los alimentos son aspectos básicos a valorar para comprender la conducta alimentaria y su impacto sobre la salud. Esta revisión realiza una integración multisensorial en referencia a la percepción de los alimentos, tanto a nivel homeostático como no homeostático, y de esta manera poder interpretar científicamente las conductas que conducen a una sobrealimentación y a proponer medidas eficaces tanto a nivel individual como poblacional en la obesidad y enfermedades metabólicas asociadas (AU)

Research in obesity has traditionally focused on prevention strategies and treatments aimed at changing lifestyle habits. However, recent research suggests that eating behavior is a habit regulated not only by homeostatic mechanisms, but also by the hedonic pathway that controls appetite and satiety processes. Cognitive, emotional, social, economic, and cultural factors, as well as organoleptic properties of food, are basic aspects to consider in order to understand eating behavior and its impact on health. This review presents a multisensory integrative view of food at both the homeostatic and non-homeostatic levels. This information will be of scientific interest to determine behavior drivers leading to overeating and, thus, to propose effective measures, at both the individual and population levels, for the prevention of obesity and associated metabolic diseases (AU)

PREVIEW (Prevention of Diabetes Through Lifestyle Intervention and Population Studies in Europe and Around the World) study in children aged 10 to 17 years: Design, methods and baseline results.

Insulin resistance (IR) in adolescence is associated with type 2 diabetes mellitus [T2DM]. The PREVIEW (Prevention of Diabetes Through Lifestyle Intervention and Population Studies in Europe and Around the World) study assessed the effectiveness of a high-protein, low-glycaemic-index diet and a moderate-protein, moderate-glycaemic-index diet to decrease IR in insulin-resistant children who were overweight or obese. Inclusion criteria were age 10 to 17 years, homeostatic model assessment of IR (HOMA-IR) ≥2.0 and overweight/obesity. In 126 children (mean ± SD age 13.6 ± 2.2 years, body mass index [BMI] z-score 3.04 ± 0.66, HOMA-IR 3.48 ± 2.28) anthropometrics, fat mass percentage (FM%), metabolic characteristics, physical activity, food intake and sleep were measured. Baseline characteristics did not differ between the groups. IR was higher in pubertal children with morbid obesity than in prepubertal children with morbid obesity (5.41 ± 1.86 vs 3.23 ± 1.86; P = .007) and prepubertal and pubertal children with overweight/obesity (vs 3.61 ± 1.60, P = .004, and vs 3.40 ± 1.50, P < .001, respectively). IR was associated with sex, Tanner stage, BMI z-score and FM%. Fasting glucose concentrations were negatively associated with Baecke sport score (r = -0.223, P = .025) and positively with daytime sleepiness (r = 0.280, P = .016) independent of sex, Tanner stage, BMI z-score and FM%. In conclusion, IR was most severe in pubertal children with morbid obesity. The associations between fasting glucose concentration and Baecke sport score and sleepiness suggest these might be possible targets for diabetes prevention.

Methylation changes and pathways affected in preterm birth: a role for SLC6A3 in neurodevelopment.

AIM: To analyze whether preterm newborns show differences in methylation patterns in comparison to full-term newborns in white blood cells. PATIENTS & METHODS: Anthropometrical, biochemical features and methylation levels of preterm newborns (n = 24) and full-term newborns (n = 22) recruited in La Paz University Hospital (Spain) were assessed at 12 months of gestational age, whereas Bayley Scale of Infant Development was evaluated at 24/36 months. RESULTS: From all the statistically significant CpGs, methylation levels of cg00997378 (SLC6A3 gene) showed the highest differences (p < 0.0001), being associated with prematurity risk factors. CONCLUSION: SLC6A3 methylation, previously related to attention-deficit/hyperactivity disorder, neuronal function and behavior, might be a potential epigenetic biomarker with value in the early diagnosis and management of neurodevelopmental diseases in newborns.

Proposed guidelines to evaluate scientific validity and evidence for genotype-based dietary advice.

Nutrigenetic research examines the effects of inter-individual differences in genotype on responses to nutrients and other food components, in the context of health and of nutrient requirements. A practical application of nutrigenetics is the use of personal genetic information to guide recommendations for dietary choices that are more efficacious at the individual or genetic subgroup level relative to generic dietary advice. Nutrigenetics is unregulated, with no defined standards, beyond some commercially adopted codes of practice. Only a few official nutrition-related professional bodies have embraced the subject, and, consequently, there is a lack of educational resources or guidance for implementation of the outcomes of nutrigenetic research. To avoid misuse and to protect the public, personalised nutrigenetic advice and information should be based on clear evidence of validity grounded in a careful and defensible interpretation of outcomes from nutrigenetic research studies. Evidence requirements are clearly stated and assessed within the context of state-of-the-art 'evidence-based nutrition'. We have developed and present here a draft framework that can be used to assess the strength of the evidence for scientific validity of nutrigenetic knowledge and whether 'actionable'. In addition, we propose that this framework be used as the basis for developing transparent and scientifically sound advice to the public based on nutrigenetic tests. We feel that although this area is still in its infancy, minimal guidelines are required. Though these guidelines are based on semi-quantitative data, they should stimulate debate on their utility. This framework will be revised biennially, as knowledge on the subject increases.

Gene methylation parallelisms between peripheral blood cells and oral mucosa samples in relation to overweight

Epigenetics has an important role in the regulation of metabolic adaptation to environmental modifications. In this sense, the determination of epigenetic changes in non-invasive samples during the development of metabolic diseases could play an important role in the procedures in primary healthcare practice. To help translate the knowledge of epigenetics to public health practice, the present study aims to explore the parallelism of methylation levels between white blood cells and buccal samples in relation to obesity and associated disorders. Blood and buccal swap samples were collected from a subsample of the Spanish cohort of the Food4Me study. Infinium HumanMethylation450 DNA Analysis was carried out for the determination of methylation levels. Standard deviation for Beta values method and concordance correlation analysis were used to select those CpG which showed best parallelism between samples. A total of 277 CpGs met the criteria and were selected for an enrichment analysis and a correlation analysis with anthropometrical and clinical parameters. From those selected CpGs, four presented high associations with BMI (cg01055691 in GAP43; r = -0.92 and rho = -0.84 for blood; r = -0.89 and rho = -0.83 for buccal sample), HOMA-IR (cg00095677 in ATP2A3; r = 0.82 and rho = -0.84 for blood; r = -0.8 and rho = -0.83 for buccal sample) and leptin (cg14464133 in ADARB2; r = -0.9182 and rho = -0.94 for blood; r = -0.893 and rho = -0.79 for buccal sample). These findings demonstrate the potential application of non-invasive buccal samples in the identification of surrogate epigenetic biomarkers and identify methylation sites in GAP43, ATP2A3 and ADARB2 genes as potential targets in relation to overweight management and insulin sensibility

Are all metabolically healthy individuals with obesity at the same risk of diabetes onset?

OBJECTIVE: To examine the risk of diabetes and the development of an unhealthy status according to metabolic health. To assess the effect of changes in metabolic health among participants with metabolically healthy obesity (MHO) on the risk of diabetes. METHODS: A total of 4,340 subjects were included. Unhealthy metabolic status was defined as having three or more risk factors of the Adult Treatment Panel-III criteria. A Cox proportional-hazard analysis was conducted to estimate the hazard ratio (HR) of developing diabetes across the change in the metabolic status of subjects with MHO. RESULTS: After 40,622 person-years of follow-up, the risk of becoming unhealthy was 1.53 times higher for participants with MHO, compared with lean or overweight healthy subjects. A greater risk of diabetes was found in MHO, but it was attributable to those who progressed to an unhealthier status over time: HR of 4.78 (95% CI: 3.38-6.78). The combination of being metabolically unhealthy and obesity heightened the risk of diabetes: HR of 10.09 (95% CI: 4.82-21.55). CONCLUSIONS: The increased risk of diabetes in MHO is attributed to the progression to an unhealthier state. "Healthy obesity" is not a permanent situation but a transitory state.

Profile of European adults interested in internet-based personalised nutrition: the Food4Me study.

PURPOSE: Personalised interventions may have greater potential for reducing the global burden of non-communicable diseases and for promoting better health and well-being across the lifespan than the conventional "one size fits all" approach. However, the characteristics of individuals interested in personalised nutrition (PN) are unclear. Therefore, the aim of this study was to describe the characteristics of European adults interested in taking part in an internet-based PN study. METHODS: Individuals from seven European countries (UK, Ireland, Germany, The Netherlands, Spain, Greece and Poland) were invited to participate in the study via the Food4Me website ( http://www.food4me.org ). Two screening questionnaires were used to collect data on socio-demographic, anthropometric and health-related characteristics as well as dietary intakes. RESULTS: A total of 5662 individuals expressed an interest in the study (mean age 40 ± 12.7; range 15-87 years). Of these, 65 % were female and 97 % were Caucasian. Overall, 13 % were smokers and 47 % reported the presence of a clinically diagnosed disease. Furthermore, 47 % were overweight or obese and 35 % were sedentary during leisure time. Assessment of dietary intakes showed that 54 % of individuals reported consuming at least 5 portions of fruit and vegetables per day, 46 % consumed more than 3 servings of wholegrains and 37 % limited their salt intake to <5.75 g per day. CONCLUSIONS: Our data indicate that individuals volunteering to participate in an internet-based PN study are broadly representative of the European adult population, most of whom had adequate nutrient intakes but could benefit from improved dietary choices and greater physical activity. Future use of internet-based PN approaches is thus relevant to a wide target audience.

Effect of TNF-Alpha on Caveolin-1 Expression and Insulin Signaling During Adipocyte Differentiation and in Mature Adipocytes.

BACKGROUND/AIMS: Tumor necrosis factor-α (TNF-α)-mediated chronic low-grade inflammation of adipose tissue is associated with obesity and insulin resistance. Caveolin-1 (Cav-1) is the central component of adipocyte caveolae and has an essential role in the regulation of insulin signaling. The effects of TNF-α on Cav-1 expression and insulin signaling during adipocyte differentiation and in mature adipocytes were studied. METHODS: 3T3-L1 cells were differentiated (21 days) in the presence TNF-α (10 ng/mL) and mature adipocytes were also treated with TNF-α for 48 hours. Cav-1 and insulin receptor (IR) gene methylation were determined as well as Cav-1, IR, PKB/AKT-2 and Glut-4 expression and activation by real time RT-PCR and western blot. Baseline and insulin-induced glucose uptake was measured by the 2-[C14]-deoxyglucose uptake assay. RESULTS: TNF-α slowed down the differentiation program, hindering the expression of some insulin signaling intermediates without fully eliminating insulin-mediated glucose uptake. In mature adipocytes, TNF-α did not compromise lipid-storage capacity, but downregulated the expression of the insulin signaling intermediates, totally blocking insulin-mediated glucose uptake. Insulin sensitivity correlated with the level of activated phospho-Cav-1 in both situations, strongly suggesting the direct contribution of Cav-1 to the maintenance of this physiological response. CONCLUSION: Cav-1 activation by phosphorylation seems to be essential for the maintenance of an active and insulin-sensitive glucose uptake.

Essential role of Nrf2 in the protective effect of lipoic acid against lipoapoptosis in hepatocytes.

Excess of saturated free fatty acids, such as palmitic acid (PA), in hepatocytes has been implicated in nonalcoholic fatty liver disease. α-Lipoic acid (LA) is an antioxidant that protects against oxidative stress conditions. We have investigated the effects of LA in the early activation of oxidative and endoplasmic reticulum stress, lipid accumulation, and Nrf2-mediated antioxidant defenses in hepatocytes treated with PA or in rats fed a high-fat diet. In primary human hepatocytes, a lipotoxic concentration of PA triggered endoplasmic reticulum stress, induced the apoptotic transcription factor CHOP, and increased the percentage of apoptotic cells. Cotreatment with LA prevented these effects. Similar results were found in mouse hepatocytes in which LA attenuated PA-mediated activation of caspase 3 and reduced lipid accumulation by decreasing PA uptake and increasing fatty acid oxidation and lipophagy, thereby preventing lipoapoptosis. Moreover, LA augmented the proliferation capacity of hepatocytes after PA challenge. Antioxidant effects of LA ameliorated reactive oxygen species production and endoplasmic reticulum stress and protected against mitochondrial apoptosis in hepatocytes treated with PA. Cotreatment with PA and LA induced an early nuclear translocation of Nrf2 and activated antioxidant enzymes, whereas reduction of Nrf2 by siRNA abolished the benefit of LA on PA-induced lipoapoptosis. Importantly, posttreatment with LA reversed the established damage induced by PA in hepatocytes, as well as preventing obesity-induced oxidative stress and lipoapoptosis in rat liver. In conclusion, our work has revealed that in hepatocytes, Nrf2 is an essential early player in the rescue of oxidative stress by LA leading to protection against PA-mediated lipoapoptosis.

Design and baseline characteristics of the Food4Me study: a web-based randomised controlled trial of personalised nutrition in seven European countries.

Improving lifestyle behaviours has considerable potential for reducing the global burden of non-communicable diseases, promoting better health across the life-course and increasing well-being. However, realising this potential will require the development, testing and implementation of much more effective behaviour change interventions than are used conventionally. Therefore, the aim of this study was to conduct a multi-centre, web-based, proof-of-principle study of personalised nutrition (PN) to determine whether providing more personalised dietary advice leads to greater improvements in eating patterns and health outcomes compared to conventional population-based advice. A total of 5,562 volunteers were screened across seven European countries; the first 1,607 participants who fulfilled the inclusion criteria were recruited into the trial. Participants were randomly assigned to one of the following intervention groups for a 6-month period: Level 0-control group-receiving conventional, non-PN advice; Level 1-receiving PN advice based on dietary intake data alone; Level 2-receiving PN advice based on dietary intake and phenotypic data; and Level 3-receiving PN advice based on dietary intake, phenotypic and genotypic data. A total of 1,607 participants had a mean age of 39.8 years (ranging from 18 to 79 years). Of these participants, 60.9 % were women and 96.7 % were from white-European background. The mean BMI for all randomised participants was 25.5 kg m(-2), and 44.8 % of the participants had a BMI ≥ 25.0 kg m(-2). Food4Me is the first large multi-centre RCT of web-based PN. The main outcomes from the Food4Me study will be submitted for publication during 2015.

Effects of lipoic acid on AMPK and adiponectin in adipose tissue of low- and high-fat-fed rats.

BACKGROUND: Lipoic acid (LA) is an antioxidant with antiobesity and antidiabetic properties. Adiponectin is an adipokine with potent anti-inflammatory and insulin-sensitizing properties. AMP-activated protein kinase (AMPK) is a key enzyme involved in cellular energy homeostasis. Activation of AMPK has been considered as a target to reverse the metabolic abnormalities associated with obesity and type 2 diabetes. AIM OF THE STUDY: The aim of this study was to determine the effects of LA on AMPK phosphorylation and adiponectin production in adipose tissue of low-fat (control diet) and high-fat diet-fed rats. RESULTS: Dietary supplementation with LA reduced body weight and adiposity in control and high-fat-fed rats. LA also reduced basal hyperinsulinemia as well as the homeostasis model assessment (HOMA) levels, an index of insulin resistance, in high-fat-fed rats, which was in part independent of their food intake lowering actions. Furthermore, AMPK phosphorylation was increased in white adipose tissue (WAT) from LA-treated rats as compared with pair-fed animals. Dietary supplementation with LA also upregulated adiponectin gene expression in WAT, while a negative correlation between adiposity-corrected adiponectin levels and HOMA index was found. Our present data suggest that the ability of LA supplementation to prevent insulin resistance in high-fat diet-fed rats might be related in part to the stimulation of AMPK and adiponectin in WAT.

Design of the nutritional therapy for overweight and obese Spanish adolescents conducted by registered dieticians: the EVASYON study.

BACKGROUND: Dietary treatment for obese adolescents should aim to ensure adequate growth and development, by reducing excessive fat mass accumulation, avoiding loss of lean body mass, improving well-being and self-esteem and preventing cyclical weight regain. The aim of this article is to describe the dietary intervention design and the methods used to evaluate nutritional knowledge and behavior in the EVASYON study (Development, implementation and evaluation of the efficacy of a therapeutic programme for overweight/obese adolescents). METHODS/DESIGN: EVASYON is a multi-centre study conducted in 5 Spanish hospital settings (Granada, Madrid, Pamplona, Santander and Zaragoza), where 204 overweight/obese Spanish adolescents were treated in groups of 9 to 11 subjects over 20 visits. The study was implemented in two stages: an intensive, calorie-restricted period for the first 9 weeks, and an extensive body-weight follow-up period for the last 11 months. A moderate energy intake restriction was applied in the intensive period according to the degree of obesity, on the basis of a balanced diet supplying 50-55% of daily energy as carbohydrates; 30-35% as fats and 10-15% as proteins. In the intensive period, adolescents were prescribed both a fixed full-day meal plan for the first three weeks and a full day meal plan with different food-choices for 6 weeks. Later, adolescents received a flexible meal plan based on food exchanges for the follow-up period until the end of the trial. Data on food intake, dietary and meal-related habits and behavior were collected by means of dietary questionnaires. To analyse nutritional knowledge, adolescents were examined regarding nutrient concepts and food adoitems for a healthy diet with the appropriate tools. Participants were given nutritional information with complementary teaching material, which was available on the EVASYON website (www.estudioevasyon.com). DISCUSSION: The dietary intervention of the EVASYON programme with a moderate calorie restriction for a limited period of time could be a good strategy in treating overweight and obese adolescents and that will be tested further. Moreover, combining fixed plan with free-choice menus may help adolescents and their families to make right decisions for every day meals.