Martinez, J.A. (José Alfredo)
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- Development of a learning-oriented computer assisted Instruction designed to improve skills in the clinical assessment of the nutritional status: a pilot evaluation(Public Library of Science, 2015) Martinez, J.A. (José Alfredo); Cuervo, M. (Marta); Garcia-de-Diego, L. (Laura)Computer assisted instruction (CAI) is an effective tool for evaluating and training students and professionals. In this article we will present a learning-oriented CAI, which has been developed for students and health professionals to acquire and retain new knowledge through the practice. A two-phase pilot evaluation was conducted, involving 8 nutrition experts and 30 postgraduate students, respectively. In each training session, the software developed guides users in the integral evaluation of a patient’s nutritional status and helps them to implement actions. The program includes into the format clinical tools, which can be used to recognize possible patient’s needs, to improve the clinical reasoning and to develop professional skills. Among them are assessment questionnaires and evaluation criteria, cardiovascular risk charts, clinical guidelines and photographs of various diseases. This CAI is a complete software package easy to use and versatile, aimed at clinical specialists, medical staff, scientists, educators and clinical students, which can be used as a learning tool. This application constitutes an advanced method for students and health professionals to accomplish nutritional assessments combining theoretical and empirical issues, which can be implemented in their academic curriculum.
- Adherence to Mediterranean diet is associated with methylation changes in inflammation-related genes in peripheral blood cells(Springer, 2017-02-08) Martinez, J.A. (José Alfredo); Riezu-Boj, J.I. (José Ignacio); Martinez-Gonzalez, M.A. (Miguel Ángel); Fito, M. (Montserrat); Milagro-Yoldi, F.I. (Fermín Ignacio); Arpon, A. (Ana); Razquin, C. (Cristina); Ros, E. (Emilio); Casas, R. (Rosa); Estruch, R. (Ramón); Corella, D. (Dolores); Salas-Salvado, J. (Jordi)Epigenetic processes, including DNA methylation, might be modulated by environmental factors such as the diet, which in turn have been associated with the onset of several diseases such as obesity or cardiovascular events. Meanwhile, Mediterranean diet (MedDiet) has demonstrated favourable effects on cardiovascular risk, blood pressure, inflammation and other complications related to excessive adiposity. Some of these effects could be mediated by epigenetic modifications. Therefore, the objective of this study was to investigate whether the adherence to MedDiet is associated with changes in the methylation status from peripheral blood cells. A subset of 36 individuals was selected within the Prevención con Dieta Mediterránea (PREDIMED)-Navarra study, a randomised, controlled, parallel trial with three groups of intervention in high cardiovascular risk volunteers, two with a MedDiet and one low-fat control group. Changes in methylation between baseline and 5 years were studied. DNA methylation arrays were analysed by several robust statistical tests and functional classifications. Eight genes related to inflammation and immunocompetence (EEF2, COL18A1, IL4I1, LEPR, PLAGL1, IFRD1, MAPKAPK2, PPARGC1B) were finally selected as changes in their methylation levels correlated with adherence to MedDiet and because they presented sensitivity related to a high variability in methylation changes. Additionally, EEF2 methylation levels positively correlated with concentrations of TNF-α and CRP. This report is apparently the first showing that adherence to MedDiet is associated with the methylation of the reported genes related to inflammation with a potential regulatory impact.
- Postprandial de novo lipogenesis and metabolic changes induced by a high-carbohydrate, low-fat meal in lean and overweight men(American Society of Nutrition, 2001) Astiasarán, I. (Iciar); Martinez, J.A. (José Alfredo); Ansorena-Artieda, D. (Diana); Forga, L. (Luis); Marques-Lopes, I. (Iva)BACKGROUND: Adjustments of carbohydrate intake and oxidation occur in both normal-weight and overweight individuals. Nevertheless, the contribution of carbohydrates to the accumulation of fat through either reduction of fat oxidation or stimulation of fat synthesis in obesity remains poorly investigated. OBJECTIVE: The objective of this study was to assess the postprandial metabolic changes and the fractional hepatic de novo lipogenesis (DNL) induced by a high-carbohydrate, low-fat meal in lean and overweight young men. DESIGN: A high-carbohydrate, low-fat meal was administered to 6 lean and 7 overweight men after a 17.5-h fast. During the fasting and postprandial periods, energy expenditure (EE), macronutrient oxidation, diet-induced thermogenesis, and serum insulin, glucose, triacylglycerol, and fatty acids were measured. To determine DNL, [1-13C]sodium acetate was infused and the mass isotopomer distribution analysis method was applied. RESULTS: After intake of the high-carbohydrate meal, the overweight men had hyperinsulinemia and higher fatty acid and triacylglycerol concentrations than did the lean men. The overweight group showed a greater EE, whereas there was no significant difference in carbohydrate oxidation between the groups. Nevertheless, the overweight men had a marginally higher protein oxidation and a lower lipid oxidation than did the lean men. DNL was significantly higher before and after meal intake in the overweight men and was positively associated with fasting serum glucose and insulin concentrations. Furthermore, postprandial DNL was positively correlated with body fat mass, EE, and triacylglycerol. CONCLUSION: After a high-carbohydrate, low-fat meal, overweight men had a lower fat oxidation and a higher fractional hepatic fat synthesis than did lean men.
- Birth weight and blood lipid levels in Spanish adolescents: Influence of selected APOE, APOC3 and PPARgamma2 gene polymorphisms. The AVENA Study(BioMed Central, 2008) Martinez, J.A. (José Alfredo); Garcia-Fuentes, M. (Miguel); Redondo-Figuero, C. (Carlos); Gonzalez-Lamuño, D. (Domingo); Ruiz, J.R. (Jonatan R.); Nova, E. (Esther); Sjöström, M. (Michael); Ortega, F.B. (Francisco B.); AVENA Study Group; Castillo, M.J. (Manuel J.); Labayen, I. (Idoya); Moreno, L.A. (Luis A.); Marti-del-Moral, A. (Amelia)Background: There is increasing evidence indicating that genes involved in certain metabolic processes of cardiovascular diseases may be of particular influence in people with low body weight at birth. We examined whether the apolipoprotein (APO) E, APOC3 and the peroxisome proliferator-activated receptor-gamma-2 (PPAR gamma 2) polymorphisms influence the association between low birth weight and blood lipid levels in healthy adolescents aged 13-18.5 years. Methods: A cross-sectional study of 502 Spanish adolescents born at term was conducted. Total (TC) and high density lipoprotein cholesterol (HDLc), triglycerides (TG), apolipoprotein (apo) A and B, and lipoprotein(a) [ Lp(a)] were measured. Low density lipoprotein cholesterol (LDLc), TC-HDLc, TC/HDLc and apoB/apoA were calculated. Results: Low birth weight was associated with higher levels of TC, LDLc, apoB, Lp(a), TC-HDLc, TC/HDLc and apoB/apoA in males with the APOE epsilon 3 epsilon 4 genotype, whereas in females, it was associated with lower HDLc and higher TG levels. In males with the APOC3 S1/S2 genotype, low birth weight was associated with lower apoA and higher Lp(a), yet this association was not observed in females. There were no associations between low birth weight and blood lipids in any of the PPAR gamma 2 genotypes. Conclusion: The results indicate that low birth weight has a deleterious influence on lipid profile particularly in adolescents with the APOE epsilon 3/epsilon 4 genotype. These findings suggest that intrauterine environment interact with the genetic background affecting the lipid profile in later life.
- Implication of miR-612 and miR-1976 in the regulation of TP53 and CD40 and their relationship in the response to specific weight-loss diets(NCBI, 2018) Martinez, J.A. (José Alfredo); Zulet, M.A. (María Ángeles); Milagro-Yoldi, F.I. (Fermín Ignacio); García-Lacarte, M. (Marcos)Background: Non-coding RNAs (i.e., miRNAs) play a role in the development of obesity and related comorbidities and the regulation of body weight. Objective: To identify candidate miRNA biomarkers throughout omics approaches in order to predict the response to specific weight-loss dietary treatments. Design: Genomic DNA and cDNA isolated from white blood cells of a subset from the RESMENA nutritional intervention study (Low-responders (LR) vs High-responders (HR)) was hybridized in Infinium Human Methylation450 BeadChip and in Illumina Human HT-12 v4 gene expression BeadChips arrays respectively. A bioinformatic prediction of putative target sites of selected miRNAs was performed by applying miRBase algorithms. HEK-293T cells were co-transfected with expression vectors containing the 3'-UTR of candidate genes to validate the binding of miRNAs to its target sites. Results: 134 miRNAs were differentially methylated between HR and LR in the methylation array, whereas 44 miRNAs were differentially expressed between both groups in the expression array. Specifically, miR-1237, miR-1976, miR-642, miR-636, miR-612 and miR-193B were simultaneously hypomethylated and overexpressed in HR. miR-612 and miR-1976 showed greatest differences in methylation and expression levels, respectively. The bioinformatic prediction revealed that TP53 was a putative target gene of miR-612 and CD40 of miR-1976. Moreover, TP53 was downregulated in the expression array when comparing HR vs LR expression levels adjusted by sex, diet, age and baseline weight, and CD40 showed a statistical trend. Furthermore, gene expression levels of TP53 and CD40 in white blood cells, when measured by qPCR, were also downregulated in HR. Finally, miR-612 and miR-1976 potently repressed TP53 and CD40 respectively by targeting its 3'-UTR regions. Conclusion: miR-612 and miR-1976 levels could be prospective biomarkers of response to specific weight-loss diets and might regulate the gene expression of TP53 and CD40.
- Nutritional Status and Nutritional Treatment Are Related to Outcomes and Mortality in Older Adults with Hip Fracture(MDPI AG, 2018) Martinez, J.A. (José Alfredo); Malafarina, V. (Vincenzo); Zulet, M.A. (María Ángeles); Reginster, J.Y. (Jean Yves); Kanis, J.A. (John A.); Cabrerizo, S. (Sonia); Bruyère, O. (Olivier)Malnutrition is very prevalent in geriatric patients with hip fracture. Nevertheless, its importance is not fully recognized. The objective of this paper is to review the impact of malnutrition and of nutritional treatment upon outcomes and mortality in older people with hip fracture. We searched the PubMed database for studies evaluating nutritional aspects in people aged 70 years and over with hip fracture. The total number of studies included in the review was 44, which analyzed 26,281 subjects (73.5% women, 83.6 +/- 7.2 years old). Older people with hip fracture presented an inadequate nutrient intake for their requirements, which caused deterioration in their already compromised nutritional status. The prevalence of malnutrition was approximately 18.7% using the Mini-Nutritional Assessment (MNA) (large or short form) as a diagnostic tool, but the prevalence was greater (45.7%) if different criteria were used (such as Body Mass Index (BMI), weight loss, or albumin concentration). Low scores in anthropometric indices were associated with a higher prevalence of complications during hospitalization and with a worse functional recovery. Despite improvements in the treatment of geriatric patients with hip fracture, mortality was still unacceptably high (30% within 1 year and up to 40% within 3 years). Malnutrition was associated with an increase in mortality. Nutritional intervention was cost effective and was associated with an improvement in nutritional status and a greater functional recovery. To conclude, in older people, the prevention of malnutrition and an early nutritional intervention can improve recovery following a hip fracture.
- Interplay of early-life nutritional programming on obesity, inflammation and epigenetic outcomes(Cambridge University Press, 2012) Martinez, J.A. (José Alfredo); Milagro-Yoldi, F.I. (Fermín Ignacio); Cordero, P. (Paul); Campión-Zabalza, J. (Javier)The huge health burden accompanying obesity is not only attributable to inadequate dietary and sedentary lifestyle habits, since a predisposing genetic make-up and other putative determinants concerning easier weight gain and fat deposition have been reported. Thus, several investigations aiming to understand energy metabolism and body composition maintenance have been performed considering the participation of perinatal nutritional programming and epigenetic processes as well as inflammation phenomena. The Developmental Origins of Health and Disease hypothesis and inheritance-oriented investigations concerning gene–nutrient interactions on energy homoeostasis and metabolic functions have suggested that inflammation could be not only a comorbidity of obesity but also a cause. There are several examples about the role of nutritional interventions in pregnancy and lactation, such as energetic deprivation, protein restriction and excess fat, which determine a cluster of disorders affecting energy efficiency in the offspring as well as different metabolic pathways, which are mediated by epigenetics encompassing the chromatin information encrypted by DNA methylation patterns, histone covalent modifications and non-coding RNA or microRNA. Epigenetic mechanisms may be boosted or impaired by dietary and environmental factors in the mother, intergenerationally or transiently transmitted, and could be involved in the obesity and inflammation susceptibility in the offspring. The aims currently pursued are the early identification of epigenetic biomarkers concerned in individual's disease susceptibility and the description of protocols for tailored dietary treatments/advice to counterbalance adverse epigenomic events. These approaches will allow diagnosis and prognosis implementation and facilitate therapeutic strategies in a personalised ‘epigenomically modelled’ manner to combat obesity and inflammation.
- The inclusion of functional foods enriched in fibre, calcium, iodine, fat-soluble vitamins and n-3 fatty acids in a conventional diet improves the nutrient profile according to the Spanish reference intake(Cambridge University Press, 2011) Astiasarán, I. (Iciar); Martinez, J.A. (José Alfredo); Ansorena-Artieda, D. (Diana); Berasategui, I. (Izaskun); Santiago, S. (Susana); Cuervo, M. (Marta); Ruiz-de-Las-Heras, A. (Arantza)Objective The growing interest in maintaining good health status through optimal nutrition has boosted the launch of a number of functional foods on the market. The objective of the present study was to theoretically evaluate the nutritional relevance of incorporating selected enriched foods in the diet. Design A 28 d dietary plan, designed to be balanced under the recommended macronutrients criteria, was used as a basal diet. Some conventional foods were exchanged with foods enriched in fibre, calcium, iodine, vitamins A, D, E or n-3 fatty acids. Setting Nutritional composition of basal and modified diets was derived and compared to the Spanish recommended intakes (RI). Results The basal diet covered the recommendations for fibre and calcium with mean intake of 28 g and 1241 mg, respectively. The current intake of salt, if iodized, or bread elaborated with this salt, allowed reaching the daily intake of iodine every day, with a mean supply of 216 μg/d and 278 μg/d, respectively. The deficient supply of vitamin E in the basal diet (mean = 8 mg/d) was covered by including enriched margarine and dairy products (mean = 15 mg/d). The low n-3 fatty acids intake in the basal diet (1·1 g/d) increased up to 1·9 g/d after the use of enriched margarine, butter and biscuits and soya drink instead of milk. Conclusions In order to improve the accomplishment of the RI iodine, vitamin E and n-3 fatty acids, interesting strategies dealing with the incorporation of enriched foods in the diet were successfully initiated.
- Chronologically scheduled snacking with high-protein products within the habitual diet in type-2 diabetes patients leads to a fat mass loss: a longitudinal study.(BioMed Central, 2011) Martinez, J.A. (José Alfredo); Zulet, M.A. (María Ángeles); Navas-Carretero, S. (Santiago); Abete, I. (Itziar)Background: Obesity is the most relevant overnutrition disease worldwide and is associated to different metabolic disorders such as insulin resistance and type-2 diabetes. Low glycemic load foods and diets and moderately high protein intake have been shown to reduce body weight and fat mass, exerting also beneficial effects on LDL-cholesterol, triglyceride concentrations, postprandial glucose curve and HDL-cholesterol levels. The present study aimed at studying the potential functionality of a series of low glycemic index products with moderately high protein content, as possible coadjuvants in the control of type-2 diabetes and weight management following a chronologically planned snacking offer (morning and afternoon). Methods: The current trial followed a single group, sequential, longitudinal design, with two consecutive periods of 4 weeks each. A total of 17 volunteers participated in the study. The first period was a free living period, with volunteers' habitual ad libitum dietary pattern, while the second period was a free-living period with structured meal replacements at breakfast, morning snack and afternoon snack, which were exchanged by specific products with moderately high protein content and controlled low glycemic index, following a scheduled temporal consumption. Blood extractions were performed at the beginning and at the end of each period (free-living and intervention). Parameters analysed were: fasting glucose, insulin, glycosylated hemoglobin, total-, HDL- and LDL-cholesterol, triglyceride, C - reactive protein and Homocysteine concentrations. Postprandial glucose and insulin were also measured. Anthropometrical parameters were monitored each 2 weeks during the whole study. Results: A modest but significant (p = 0.002) reduction on body weight (1 kg) was observed during the intervention period, mainly due to the fat mass loss (0.8 kg, p = 0.02). This weight reduction was observed without apparently associated changes in total energy intake. None of the biochemical biomarkers measured was altered throughout the whole study. Conclusions: Small changes in the habitual dietary recommendations in type-2 diabetes patients by the inclusion of specific low-glycemic, moderately high-protein products in breakfast, morning and afternoon snacks may promote body weight and fat-mass loss, without apparently altering biochemical parameters and cardiovascular risk-related factors.
- Arylesterase activity is associated with antioxidant intake and paraoxonase-1 (PON1) gene methylation in metabolic syndrome patients following an energy restricted diet(2014) Martinez, J.A. (José Alfredo); Zulet, M.A. (María Ángeles); Sanchez-Muniz, F.J. (Francisco J.); Mansego-Talavera, M.L. (María Luisa); Iglesia, R. (Rocío) de laThe arylesterase (ARE) activity linked to the paraoxonase-1 (PON1) gene is known to protect lipoproteins from oxidation and provide defense against metabolic syndrome (MetS) and cardiovascular diseases. The epigenetic regulation of enzymatic activities is gaining importance nowadays. This research aimed to assess the potential relationships between the ARE activity with the methylation levels of the PON1 gene transcriptional regulatory region, anthropometrics, biochemical markers and antioxidant dietary components. Forty-seven subjects (47 ± 10 y.o; BMI 36.2 ± 3.8 kg/m2; 46.8 % female) with MetS features, who followed a sixmonth energy-restricted dietary weight-loss intervention, were included in this study (www.clinicaltrials.gov; NCT01087086). Anthropometric, biochemical, enzymatic and dietary data were assessed using validated procedures. PON1 transcriptional regulatory region methylation was analyzed by a microarray technical approach. Volunteers reduced ARE activity in parallel with body weight (p = 0.005), BMI (p = 0.006), total fat mass (p = 0.020), diastolic blood pressure (p = 0.018), mean blood pressure (p = 0.022) and triglycerides (p = 0.014). Methylation levels of some CpG sites of the PON1 gene correlated negatively with ARE activity (p < 0.05). Interestingly, dietary vitamin C (p = 0.001), tocopherols (p = 0.009) and lycopene (p = 0.038) were positively associated with ARE activity and showed an inverse correlation (p = 0.004, p = 0.029 and p = 0.021, respectively) with the methylation of some selected CpG sites of the PON1 gene. In conclusion, ARE activity decreased in parallel with MetS-related markers associated to the energy restriction, while dietary antioxidants might enhance the ARE activity by lowering the PON1 gene methylation in patients with MetS features.