High-Fat Diet-Induced Obesity Increases Brain Mitochondrial Complex I and Lipoxidation-Derived Protein Damage.

Obesity is a risk factor for highly prevalent age-related neurodegenerative diseases, the pathogenesis of whichinvolves mitochondrial dysfunction and protein oxidative damage. Lipoxidation, driven by high levels of peroxidizable unsaturated fatty acids and low antioxidant protection of the brain, stands out as a significant risk factor. To gain information on the relationship between obesity and brain molecular damage, in a porcine model of obesity we evaluated (1) the level of mitochondrial respiratory chain complexes, as the main source of free radical generation, by Western blot; (2) the fatty acid profile by gas chromatography; and (3) the oxidative modification of proteins by mass spectrometry. The results demonstrate a selectively higher amount of the lipoxidation-derived biomarker malondialdehyde-lysine (MDAL) (34% increase) in the frontal cortex, and positive correlations between MDAL and LDL levels and body weight. No changes were observed in brain fatty acid profile by the high-fat diet, and the increased lipid peroxidative modification was associated with increased levels of mitochondrial complex I (NDUFS3 and NDUFA9 subunits) and complex II (flavoprotein). Interestingly, introducing n3 fatty acids and a probiotic in the high-fat diet prevented the observed changes, suggesting that dietary components can modulate protein oxidative modification at the cerebral level and opening new possibilities in neurodegenerative diseases' prevention.

Antihypertensive Effects of an Optimized Aged Garlic Extract in Subjects with Grade I Hypertension and Antihypertensive Drug Therapy: A Randomized, Triple-Blind Controlled Trial.

The use of garlic (Allium sativum) for treating arterial hypertension has been recognized as effective for several decades. However, tolerance to treatment is low, and several technological modifications have been developed to improve its tolerability, such as the aging process at controlled temperature and humidity. This study aims to validate the antihypertensive effects of an optimized extract of aged black garlic with low doses of s-allyl-cysteine (SAC) in a Grade I hypertensive population with drug treatment. A randomized, triple-blind, placebo-controlled parallel trial was developed, where a daily supplementation with 0.25 mg/day of SAC for 12 weeks was performed. A reduction in systolic and diastolic blood pressure of 1.8 mmHg (0.7 to 4.1 95% CI) and 1.5 mmHg (0.3 to 3.0 95% CI), respectively, was observed. Similarly, an increase in blood nitric oxide (10.3 µM, 1.1 to 19.5 95% CI) and antioxidant capacity (7 × 10-3 µM TE/min, (1.2 to 13 × 10-3 95% CI) and a reduction in uric acid levels (-0.3 mg/dL, -0.5 to -0.001 95% CI) and ACE activity (-9.3 U/L; -18.4 to -0.4 95% CI) were observed. No changes in endothelial function and inflammatory cytokines were observed. It was concluded that low-dose SAC supplementation in an optimized black-garlic extract allows for an extra-significant reduction in blood pressure in a Grade I hypertensive population receiving drug treatment.

Associations of Dietary Intake and Nutrient Status with Micronutrient and Lipid Composition in Breast Milk of Donor Women.

The influence of the diet and nutritional status of milk donors on the nutritional composition of donor human milk (DHM) is unknown. The present study aimed to determine the nutritional profile of DHM and the associations between donors' dietary intake and nutritional status and the micronutrient and lipid composition in DHM. For this purpose, 113 donors completed a food frequency questionnaire, provided a five-day weighed dietary record, and collected milk for five consecutive days. Nutrient determinations in donors' erythrocytes, plasma, urine, and milk were performed. Multiple linear regressions were conducted for the evaluation of the associations. We highlight the following results: DHM docosahexaenoic acid (DHA) was positively associated with donors' plasma DHA content and donors' DHA intake (R2 0.45, p < 0.001). For every 1 g/day DHA intake, an increase of 0.38% in DHA content and 0.78% in total omega-3 content was observed in DHM (R2 0.29, p < 0.001). DHM saturated fatty acids were positively associated with erythrocyte dimethyl acetals, plasma stearic acid, trans fatty acids intake, and breastfeeding duration and negatively associated with erythrocyte margaroleic acid (R2 0.34, p < 0.01). DHM cholecalciferol was associated with plasma cholecalciferol levels and dairy intake (R2 0.57, p < 0.01). Other weaker associations were found for free thiamin, free riboflavin, pyridoxal, dehydroascorbic acid, and the lipid profile in DHM. In conclusion, the diet and nutritional status of donors influence the fatty acid profile and micronutrient content of DHM.

Hippocampal neurogenesis and Arc expression are enhanced in high-fat fed prepubertal female pigs by a diet including omega-3 fatty acids and Bifidobacterium breve CECT8242.

PURPOSE: Obesity during childhood has become a pandemic disease, mainly caused by a diet rich in sugars and fatty acids. Among other negative effects, these diets can induce cognitive impairment and reduce neuroplasticity. It is well known that omega-3 and probiotics have a beneficial impact on health and cognition, and we have hypothesized that a diet enriched with Bifidobacterium breve and omega-3 could potentiate neuroplasticity in prepubertal pigs on a high-fat diet. METHODS: Young female piglets were fed during 10 weeks with: standard diet (T1), high-fat (HF) diet (T2), HF diet including B. breve CECT8242 (T3) and HF diet including the probiotic and omega-3 fatty acids (T4). Using hippocampal sections, we analyzed by immunocytochemistry the levels of doublecortin (DCX) to study neurogenesis, and activity-regulated cytoskeleton-associated protein (Arc) as a synaptic plasticity related protein. RESULTS: No effect of T2 or T3 was observed, whereas T4 increased both DCX+ cells and Arc expression. Therefore, a diet enriched with supplements of B. breve and omega-3 increases neurogenesis and synaptic plasticity in prepubertal females on a HF diet from nine weeks of age to sexual maturity. Furthermore, the analysis of serum cholesterol and HDL indicate that neurogenesis was related to lipidic demand in piglets fed with control or HF diets, but the neurogenic effect induced by the T4 diet was exerted by mechanisms independent of this lipidic demand. CONCLUSION: Our results show that the T4 dietary treatment is effective in potentiating neural plasticity in the dorsal hippocampus of prepubertal females on a HF diet.

PKN1 Kinase: A Key Player in Adipocyte Differentiation and Glucose Metabolism.

Adipocyte dysfunction is the driver of obesity and correlates with insulin resistance and the onset of type 2 diabetes. Protein kinase N1 (PKN1) is a serine/threonine kinase that has been shown to contribute to Glut4 translocation to the membrane and glucose transport. Here, we evaluated the role of PKN1 in glucose metabolism under insulin-resistant conditions in primary visceral adipose tissue (VAT) from 31 patients with obesity and in murine 3T3-L1 adipocytes. In addition, in vitro studies in human VAT samples and mouse adipocytes were conducted to investigate the role of PKN1 in the adipogenic maturation process and glucose homeostasis control. We show that insulin-resistant adipocytes present a decrease in PKN1 activation levels compared to nondiabetic control counterparts. We further show that PKN1 controls the adipogenesis process and glucose metabolism. PKN1-silenced adipocytes present a decrease in both differentiation process and glucose uptake, with a concomitant decrease in the expression levels of adipogenic markers, such as PPARγ, FABP4, adiponectin and CEBPα. Altogether, these results point to PKN1 as a regulator of key signaling pathways involved in adipocyte differentiation and as an emerging player of adipocyte insulin responsiveness. These findings may provide new therapeutic approaches for the management of insulin resistance in type 2 diabetes.

Human Milk Composition and Nutritional Status of Omnivore Human Milk Donors Compared with Vegetarian/Vegan Lactating Mothers.

Women of childbearing age in Western societies are increasingly adopting vegetarian diets. These women are sometimes rejected as milk donors, but little about the composition of their milk is known. The present study aimed to compare the intake, nutritional status, and nutritional composition of human milk from omnivore human milk donors (Donors) and vegetarian/vegan lactating mothers (Veg). Milk, blood, and urine samples from 92 Donors and 20 Veg were used to determine their fatty acid profiles, as well as vitamins and minerals. In a representative sample of both groups, we also determined the lipid class profile as a distribution of neutral and polar lipids, the molecular species of triacylglycerols, and the relative composition of phospholipids in their milk. A dietary assessment was conducted with a five-day dietary record (while considering the intake of supplements). We highlight the following results, expressed as the mean (SE), for the Veg vs. Donors: (1) Their docosahexaenoic acid (DHA) intake was 0.11 (0.03) vs. 0.38 (0.03) g/day; the plasma DHA was 0.37 (0.07) vs. 0.83 (0.06)%; and the milk DHA was 0.15 (0.04) vs. 0.33 (0.02)%. (2) Their milk B12 levels were 545.69 (20.49) vs. 482.89 (4.11) pM; 85% of the Veg reported taking B12 supplements (mean dose: 312.1 mcg/day); and the Veg group showed no differences with Donors in terms of total daily intake or plasma B12. (3) Their milk phosphatidylcholine levels were 26.88 (0.67) vs. 30.55 (1.10)%. (4) Their milk iodine levels were 126.42 (13.37) vs. 159.22 (5.13) mcg/L. In conclusion, the Vegs' milk was shown to be different from the Donors' milk, mainly due to its low DHA content, which is concerning. However, raising awareness and ensuring proper supplementation could bridge this gap, as has already been achieved for cobalamin.

Assessment of Iodine Concentration in Human Milk from Donors: Implications for Preterm Infants.

Preterm infants are particularly vulnerable to developing iodine deficiency. Donor human milk (DHM) is the preferred feeding option if the mother's own milk (MOM) is not available, but information on DHM iodine concentration (DHMIC) is lacking. Hence, we aimed to assess DHMIC to further evaluate the adequacy of iodine provision in preterm infants. Finally, associations that might influence DHMIC were studied. In 113 donors, we measured iodine intake by evaluating dietary records for five consecutive days with the DIAL® Software. From the second day of dietary record, donors provided human milk samples (at least one per day) for four consecutive days. Daily human milk samples were analyzed for DHMIC. A DHMIC ≥ 200 µg/L was considered an adequate iodine content for preterm infants. DHMIC and urine iodine concentration (UIC) were determined using ICP-MS. In our study, 83.2% of donors had a full-term infant. Breastfeeding time range was 1.5−49.4 months. During the dietary record, 55.8% took iodine-containing supplements, providing 40−200 µg/day of iodine. The medians (p25, p75) UIC and DHMIC were 112.4 (75.8, 160.1) and 148.5 (97.6, 206.1) µg/L, respectively. In this iodine-sufficient population, 70% had a DHMIC of <200 µg/L. Donors' intake of iodine-containing supplements was associated with higher DHMIC.

PEGASO e-Diary: User Engagement and Dietary Behavior Change of a Mobile Food Record for Adolescents.

Background: Obesity amongst children and adolescents is becoming a major health problem globally and mobile food records can play a crucial role in promoting healthy dietary habits. Objective: To describe the methodology for the implementation of the e-Diary mobile food record, to assess its capability in promoting healthy eating habits, to evaluate the factors associated with its usage and engagement. Methods: This is a descriptive study that compared the characteristics of participants engaged in the e-Diary, which was part of the PEGASO project in which an app to provide proactive health promotion was given to 365 students at 4 European sites enrolled during October to December 2016: England (UK), Scotland (UK), Lombardy (Italy), and Catalonia (Spain). The e-Diary tracked the users' dietary habits in terms of food groups, dietary indexes, and 6 dietary target behaviors relating to consumption of: fruit; vegetable; breakfast; sugar-sweetened beverages; fast-food; and snacks. The e-Diary provided also personalized suggestions for the next meal and gamification. Results: The e-Diary was used for 6 months by 357 adolescents (53.8% females). The study showed that females used the e-Diary much more than males (aOR 3.8, 95% CI 1.6-8.8). Participants aged 14 years were more engaged in the e-Diary than older age groups (aOR 5.1, 95% CI 1.4-18.8) as were those with a very good/excellent self-perceived health status compared to their peers with fair/poor health perception (aOR 4.2, 95% CI 1.3-13.3). Compared to the intervention sites, those living in Catalonia (aOR 13.2 95% CI 2.5-68.8) were more engaged. In terms of behavior change, a significant positive correlation between fruit (p < 0.0001) and vegetables (p = 0.0087) intake was observed in association with increased engagement in the e-Diary. Similarly, adolescents who used the app for more than 2 weeks had significantly higher odds of not skipping breakfast over the study period (aOR 2.5, 95% CI 1.0-6.3). Conclusions: The users highly engaged with the e-Diary were associated with improved dietary behaviors: increased consumption of fruit and vegetables and reduced skipping of breakfast. Although the overall usage of the e-Diary was high during the first weeks, it declined thereafter. Future applications should foster user engagement, particularly targeting adolescents at high risk. Clinical Trial Registration: https://www.clinicaltrials.gov/, identifier: NCT02930148.

Colonic Microbiota Profile Characterization of the Responsiveness to Dietary Fibre Treatment in Hypercholesterolemia.

This study aimed to determine how the microbiota profile might be predisposed to a better response in blood lipid profiles due to dietary fibre supplementation. A three-arm intervention study that included three different fibre types (mainly insoluble, soluble, and antioxidant fibre) supplemented (19.2 g/day) during 2 months in individuals with hypercholesterolemia was developed. Changes in faecal microbiota and blood lipid profile after fibre supplementation were determined. In all volunteers, regardless of fibre type, an increase in the abundance of Bifidobacterium was observed, and similarly, an inverse relationship between faecal propionic acid and blood LDL-cholesterol, LDL particle size, and LDL/HDL particle ratio (p-values 0.0067, 0.0002, and 0.0067, respectively) was observed. However, not all volunteers presented an improvement in lipid profile. The non-responders to fibre treatment showed a decrease in microbiota diversity (Shannon and Simpson diversity index p-values of 0.0110 and 0.0255, respectively) after the intervention; where the reduction in short-chain fatty acids (SCFAs) producing bacterial genera such as Clostridium XIVa and Ruminococcus after dietary fibre treatment was the main difference. It was concluded that the non-responsiveness to dietary fibre treatment might be mediated by the lack of ability to maintain a stable SCFA producing bacteria diversity and composition after extra fibre intake.

In Vivo Anti-Inflammatory Effects and Related Mechanisms of Processed Egg Yolk, a Potential Anti-Inflammaging Dietary Supplement.

Egg-yolk based supplements have demonstrated biological effects. We have developed a novel processed egg-yolk (PEY) complement, and we have tested whether it has inflammation modulatory properties. These were evaluated in a lipopolysaccharide (LPS)-challenge in 1-month male rats by in vivo circulating cytokine profiles measured by multiplexing techniques. Cell culture was used to explore ex vivo properties of derived serum samples. We explored growth factor composition, and mass-spectrometry metabolome and lipidome analyses of PEY to characterize it. PEY significantly prevented LPS-induced increase in IL-1 ß, TNF-α, and MCP-1. Further, serum from PEY-treated animals abrogated LPS-induced iNOS build-up of the Raw 264.7 macrophage-like cell line. Immunochemical analyses demonstrated increased concentrations of insulin-like growth factor 1 (IGF-1), connective tissue growth factor (CTGF), and platelet-derived growth factor (PDGF) in the extract. PEY vs. egg-yolk comparative metabolomic analyses showed significative differences in the concentrations of at least 140 molecules, and in 357 in the lipidomic analyses, demonstrating the complexity of PEY. Globally, PEY acts as an orally-bioavailable immunomodulatory extract that may be of interest in those conditions associated with disarranged inflammation, such as inflammaging.

Dietary intake of bioactive ingredients impacts liver and adipose tissue transcriptomes in a porcine model of prepubertal early obesity.

Global prevalence of obesity has increased to epidemic proportions over the past 40 years, with childhood obesity reaching alarming rates. In this study, we determined changes in liver and adipose tissue transcriptomes of a porcine model for prepubertal early obesity induced by a high-calorie diet and supplemented with bioactive ingredients. A total of 43 nine-weeks-old animals distributed in four pens were fed with four different dietary treatments for 10 weeks: a conventional diet; a western-type diet; and a western-type diet with Bifidobacterium breve and rice hydrolysate, either adding or not omega-3 fatty acids. Animals fed a western-type diet increased body weight and total fat content and exhibited elevated serum concentrations of cholesterol, whereas animals supplemented with bioactive ingredients showed lower body weight gain and tended to accumulate less fat. An RNA-seq experiment was performed with a total of 20 animals (five per group). Differential expression analyses revealed an increase in lipogenesis, cholesterogenesis and inflammatory processes in animals on the western-type diet while the supplementation with bioactive ingredients induced fatty acid oxidation and cholesterol catabolism, and decreased adipogenesis and inflammation. These results reveal molecular mechanisms underlying the beneficial effects of bioactive ingredient supplementation in an obese pig model.

Adipose Tissue Protein Glycoxidation is Associated with Weight-Loss Potential.

OBJECTIVE: This study aimed to characterize the differences in protein oxidation biomarkers in adipose tissue (AT) as an indicator of AT metabolism and bariatric surgery weight-loss success. METHODS: A human model, in which sixty-five individuals with obesity underwent bariatric surgery, and a diet-induced obesity animal model, in which animals were treated for 2 months with normocaloric diets, were analyzed to determine the associations between AT protein oxidation and body weight loss. Protein oxidative biomarkers were determined by gas chromatography/mass spectrometry in AT from human volunteers before the surgery, as well as 2 months after a diet treatment in the animal model. RESULTS: The levels of carboxyethyl-lysine (CEL) and 2-succinocystein (2SC) in both visceral and subcutaneous AT before the surgery directly correlated with greater weight loss in both human and animal models. 2SC levels in subcutaneous AT greater than 4.7 × 106  µmol/mol lysine (95% CI: 3.4 × 106 to 6.0 × 106 ) may predict greater weight loss after bariatric surgery (receiver operating characteristic curve area = 0.8222; P = 0.0047). Additionally, it was observed that individuals with diabetes presented lower levels of CEL and 2SC in subcutaneous AT (P = 0.0266 and P = 0.0316, respectively) compared with individuals without diabetes. CONCLUSIONS: CEL and 2SC in AT are useful biomarkers of AT metabolism and predict the individual's ability to reduce body weight after bariatric surgery.

Location-dependent effects of trauma on oxidative stress in humans.

Though circulating antioxidant capacity in plasma is homeostatically regulated, it is not known whether acute stressors (i.e. trauma) affecting different anatomical locations could have quantitatively different impacts. For this reason, we evaluated the relationship between the anatomical location of trauma and plasma total antioxidant capacity (TAC) in a prospective study, where the anatomical locations of trauma in polytraumatic patients (n = 66) were categorized as primary affecting the brain -traumatic brain injury (TBI)-, thorax, abdomen and pelvis or extremities. We measured the following: plasma TAC by 2 independent methods, the contribution of selected antioxidant molecules (uric acid, bilirubin and albumin) to these values and changes after 1 week of progression. Surprisingly, TBI lowered TAC (919 ± 335 µM Trolox equivalents (TE)) in comparison with other groups (thoracic trauma 1187 ± 270 µM TE; extremities 1025 ± 276 µM TE; p = 0.004). The latter 2 presented higher hypoxia (PaO2/FiO2 272 ± 87 mmHg) and hemodynamic instability (inotrope use required in 54.5%) as well. Temporal changes in TAC are also dependent on anatomical location, as thoracic and extremity trauma patients' TAC values decreased (1187 ± 270 to 1045 ± 263 µM TE; 1025 ± 276 to 918 ± 331 µM TE) after 1 week (p < 0.01), while in TBI these values increased (919 ± 335 to 961 ± 465 µM TE). Our results show that the response of plasma antioxidant capacity in trauma patients is strongly dependent on time after trauma and location, with TBI failing to induce such a response.

TSHB mRNA is linked to cholesterol metabolism in adipose tissue.

Subclinical hypothyroidism is known to be associated with increased serum cholesterol. Since thyroid-stimulating hormone (TSH) exerts an inductor effect on cholesterol biosynthesis, we aimed to investigate the relationship between TSH mRNA and cholesterol metabolism in human adipose tissue (AT). Cross-sectionally, AT TSH-ß (TSHB) mRNA was evaluated in 4 independent cohorts in association with serum total and LDL cholesterol, and AT lipidomics. Longitudinally, the effects of statins and of diet and exercise on AT TSHB mRNA were also examined. The bidirectional relationship between cholesterol and TSHB were studied in isolated human adipocytes. TSHB mRNA was consistently detected in AT from euthyroid subjects, and positively associated with serum total- and LDL-cholesterol, and with AT-specific cholesterol metabolism-associated lipids [arachidonoyl cholesteryl ester, C8-dihydroceramide, N-stearoyl-d-sphingosine, and GlcCer(18:0, 24:1)]. Reduction of cholesterol with statins and with diet and exercise interventions led to decreased TSHB mRNA in human AT, whereas excess cholesterol up-regulated TSHB mRNA in human adipocytes. In addition, recombinant human TSH α/ß administration resulted in increased HMGCR mRNA levels in human adipocytes. In mice, subcutaneous AT Tshb expression levels correlated directly with circulating cholesterol levels. In summary, current results provide novel evidence of TSHB as a paracrine factor that is modulated in parallel with cholesterol metabolism in human AT.-Moreno-Navarrete, J. M., Moreno, M., Ortega, F., Xifra, G., Hong, S., Asara, J. M., Serrano, J. C. E., Jové, M., Pissios, P., Blüher, M., Ricart, W., Portero-Otin, M., Fernández-Real, J. M. TSHB mRNA is linked to cholesterol metabolism in adipose tissue.

Exposure to minimally processed pear and melon during shelf life could modify the pathogenic potential of Listeria monocytogenes.

Survival and virulence of foodborne pathogens can be influenced by environmental factors such as the intrinsic properties of food as well as the extrinsic properties that contribute to food shelf life (e.g., temperature and gas atmosphere). The direct contribution of food matrix characteristics on the survival of L. monocytogenes during fresh-cut fruit shelf life is not very well understood. In addition, the gastrointestinal tract is the primary route of listeriosis infection and penetration of the intestinal epithelial cell barrier is the first step in the infection process. Hence, the pathogenic potential of L. monocytogenes, measured as the capability for the organism to survive a simulated gastrointestinal tract and the proportion of cells able to subsequently adhere to and invade differentiated Caco-2 cells, subjected to fresh-cut pear and melon shelf life, was investigated. Samples were inoculated, stored at 10 °C for 7 days and evaluated after inoculation and again after 2 and 7 days of storage. A decrease in L. monocytogenes' capacity to survive a simulated gastrointestinal tract was observed with increasing storage time, regardless of the fruit matrix evaluated. Furthermore, L. monocytogenes placed on fresh-cut pear and melon was subjected to an attachment and invasion assay after crossing the simulated gastrointestinal tract. After inoculation, pathogen on fresh-cut pear showed 5-fold more capacity to adhere to Caco-2 cells than pathogen on fresh-cut melon. After 2 days of storage, L. monocytogenes grown on fresh-cut melon showed similar adhesive capacity (1.11%) than cells grown on pear (1.83%), but cells grown on melon had the higher invasive capacity (0.0093%). We can conclude that minimally processed melon could represent a more important hazard than pear under the studied shelf life.

The distribution of carotenoids in hens fed on biofortified maize is influenced by feed composition, absorption, resource allocation and storage.

Carotenoids are important dietary nutrients with health-promoting effects. The biofortification of staple foods with carotenoids provides an efficient delivery strategy but little is known about the fate and distribution of carotenoids supplied in this manner. The chicken provides a good model of human carotenoid metabolism so we supplemented the diets of laying hens using two biofortified maize varieties with distinct carotenoid profiles and compared the fate of the different carotenoids in terms of distribution in the feed, the hen's livers and the eggs. We found that after a period of depletion, pro-vitamin A (PVA) carotenoids were preferentially diverted to the liver and relatively depleted in the eggs, whereas other carotenoids were transported to the eggs even when the liver remained depleted. When retinol was included in the diet, it accumulated more in the eggs than the livers, whereas PVA carotenoids showed the opposite profile. Our data suggest that a transport nexus from the intestinal lumen to the eggs introduces bottlenecks that cause chemically-distinct classes of carotenoids to be partitioned in different ways. This nexus model will allow us to optimize animal feed and human diets to ensure that the health benefits of carotenoids are delivered in the most effective manner.

Oral intake of genetically engineered high-carotenoid corn ameliorates hepatomegaly and hepatic steatosis in PTEN haploinsufficient mice.

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease. Here we show that a mouse model of haploinsufficiency in the lipid and protein phosphatase and tensin homolog protein (PTEN(+/-)) exhibits hepatomegaly, increased liver lipogenic gene expression (SREBP-1C and PPARγ) and hepatic lesions analogous to human NAFLD. The livers of PTEN(+/-) mice also contained lower levels of retinoic acid (RA) than normal, similarly to human NAFLD patients. The RA signaling pathway thus offers a novel therapeutic target for the treatment of NAFLD although the impact of nutrition in this context is unclear. We therefore fed PTEN(+/-) mice for 36weeks a diet containing genetically engineered high-carotenoid corn (HCAR) to investigate its potential beneficial effects on the hepatic symptoms of NAFLD. The HCAR diet reduced hepatomegaly and promoted the repartitioning of fatty acids in the liver, away from triacylglycerol storage. At the molecular level, the HCAR diet clearly reduced lipogenic gene expression, boosted catabolism, and increased hepatic RA levels. These results set the stage for human trials to evaluate the use of high-carotenoid foods for the reduction or prevention of steatosis in NAFLD.

Effect of Dietary Bioactive Compounds on Mitochondrial and Metabolic Flexibility.

Metabolic flexibility is the capacity of an organism to adequately respond to changes in the environment, such as nutritional input, energetic demand, etc. An important player in the capacity of adaptation through different stages of metabolic demands is the mitochondrion. In this context, mitochondrial dysfunction has been attributed to be the onset and center of many chronic diseases, which are denoted by an inability to adapt fuel preferences and induce mitochondrial morphological changes to respond to metabolic demands, such as mitochondrial number, structure and function. Several nutritional interventions have shown the capacity to induce changes in mitochondrial biogenesis/degradation, oxidative phosphorylation efficiency, mitochondrial membrane composition, electron transfer chain capacity, etc., in metabolic inflexibility states that may open new target options and mechanisms of action of bioactive compounds for the treatment of metabolic diseases. This review is focused in three well-recognized food bioactive compounds that modulate insulin sensitivity, polyphenols, ω-3 fatty acids and dietary fiber, by several mechanism of action, like caloric restriction properties and inflammatory environment modulation, both closely related to mitochondrial function and dynamics.

Nutridynamics: mechanism(s) of action of bioactive compounds and their effects.

Mechanism of action of bioactive compounds may be multiple, especially in the food matrix. Therefore, the interplay between these compounds and hosts' physiology, and the consequences of its continuous intake should be considered. In analogy with pharmacodynamics, the bioactive compounds should have both defined targets and mechanisms of action. However, several essential differences arise when considering the heterogeneous nature of the food matrix, the multiplicity of mechanisms and the variety of responses. In order to ascertain a potential mechanism of activity, one should consider both the intended use of the food, the biomarker that will support this claim and previous evidences, examined from current information sources. Once these have been examined, several experimental strategies should be considered, ranging from the choice of preclinical or experimental model, the use of samples from pilot interventional studies and the application of system's biology derived techniques, such as transcriptomics or metabolomics.

PEGASO: A Personalised and Motivational ICT System to Empower Adolescents Towards Healthy Lifestyles.

Unhealthy alimentary behaviours and physical inactivity habits are key risk factors for major non communicable diseases. Several researches demonstrate that juvenile obesity can lead to serious medical conditions, pathologies and have important psycho-social consequences. PEGASO is a multidisciplinary project aimed at promoting healthy lifestyles among teenagers through assistive technology. The core of this project is represented by the ICT system, which allows providing tailored interventions to the users through their smartphones in order to motivate them. The novelty of this approach consists of developing a Virtual Individual Model (VIM) for user characterization, which is based on physical, functional and behavioural parameters opportunely selected by experts. These parameters are digitised and updated thanks to the user monitoring through smartphone; data mining algorithms are applied for the detection of activity and nutrition habits and this information is used to provide personalised feedback. The user interface will be developed using gamified approaches and integrating serious games to effectively promote health literacy and facilitate behaviour change.