Zulet, M.A. (María Ángeles)
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- 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.
- 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.
- Dietary total antioxidant capacity and obesity in children and adolescents(Informa Healthcare, 2010) Martinez, J.A. (José Alfredo); Martinez-Gonzalez, M.A. (Miguel Ángel); Patiño-García, A. (Ana); Moreno-Aliaga, M. J. (María Jesús); Zulet, M.A. (María Ángeles); Ochoa, M.C. (María Carmen); Azcona-San-Julian, M.C. (María Cristina); Puchau, B. (Blanca); Chueca, M. (María); Oyarzabal, M. (M.); Marti-del-Moral, A. (Amelia)Dietary antioxidant intake has been suggested to protect against oxidative damage and related clinical complications. The aim of this study was to assess the potential relationships between the dietary total antioxidant capacity (TAC) and obesity-related features in children and adolescents. Anthropometric variables from 369 children and adolescents were measured (184 obese and 185 control). A validated food-frequency questionnaire was used to calculate the TAC and the daily nutrient and energy intake. Dietary TAC showed positive associations with fiber, folic acid, magnesium, and vitamins A, C and E. BMI, SDS-BMI and total body fat were inversely associated with dietary TAC only in obese subjects. These data suggest that dietary TAC may be a potential indicator of the risk to develop obesity-related features and could be considered as a useful method in assessing antioxidant intake.
- Relationship of visceral adipose tissue with surrogate insulin resistance and liver markers in individuals with metabolic syndrome chronic complications(Sage journals, 2020) Martinez, J.A. (José Alfredo); Corbella, E. (Emili); Martinez-Gonzalez, M.A. (Miguel Ángel); Fito, M. (Montserrat); Konieczna, J. (Jadwiga); Daimiel, L. (Lidia); Tinahones, F.J. (Francisco J.); Zulet, M.A. (María Ángeles); Tur, J.A. (Josep A.); Toledo, E. (Estefanía); Romaguera, D. (Dora); Macías-González, M. (Manuel); Ros, E. (Emilio); Estruch, R. (Ramón); Corella, D. (Dolores); Abete, I. (Itziar); Mascaró, C.M. (Catalina M.); Pinto, X. (Xavier); Salas-Salvado, J. (Jordi); Sayon-Orea, C. (Carmen); Bullón-Vela, M. V. (María Vanessa)Background: Visceral adipose tissue (VAT) has a hazardous influence on systemic inflammation, insulin resistance and an adverse metabolic profile, which increases the risk of developing non-alcoholic fatty liver disease (NAFLD) and chronic complications of diabetes. In our study we aimed to evaluate the association of VAT and the triglyceride glucose (TyG) as a proxy of insulin resistance surrogated with metabolic and liver risk factors among subjects diagnosed with metabolic syndrome (MetS). Methods: A cross-sectional study was performed including 326 participants with MetS (55– 75years) from the PREDIMED-Plus study. Liver-status markers, VAT and TyG were assessed. Participants were stratified by tertiles according to VAT (n=254) and TyG (n=326). A receiver operating characteristic curve was used to analyse the efficiency of TyG for VAT. Results: Subjects with greater visceral fat depots showed worse lipid profile, higher homeostatic model assessment for insulin resistance (HOMA-IR), TyG, alanine transaminase (ALT), fibroblast growth factor-21 (FGF-21), fatty liver index (FLI) and hepatic steatosis index (HSI) compared with participants in the first tertile. The multi-adjusted linear-regression analyses indicated that individuals in the third tertile of TyG (>9.1−10.7) had a positive association with HOMA-IR [β=3.07 (95% confidence interval (CI) 2.28−3.86; p trend<0.001)], ALT [β=7.43 (95% CI 2.23−12.63; p trend=0.005)], gamma glutamyl transferase (GGT) [β=14.12 (95% CI 3.64−24.61; p trend=0.008)], FGF-21 [β=190.69 (95% CI 93.13−288.25; p trend<0.001)], FLI [β=18.65 (95% CI 14.97−22.23; p trend<0.001)] and HSI [β=3.46 (95% CI, 2.23−4.68; p trend<0.001)] versus participants from the first tertile. Interestingly, the TyG showed the largest area under the receiver operating curve (AUC) for women (AUC=0.713; 95% CI 0.62−0.79) compared with men (AUC=0.570; 95% CI 0.48−0.66). Conclusions: A disrupted VAT enlargement and impairment of TyG are strongly associated with liver status and cardiometabolic risk factors linked with NAFLD in individuals diagnosed with MetS. Moreover, the TyG could be used as a suitable and reliable marker estimator of VAT.
- Interplay of atherogenic factors, protein intake and betatrophin levels in obese–metabolic syndrome patients treated with hypocaloric diets(Nature Publishing Group, 2015) Martinez, J.A. (José Alfredo); Casanueva, F.F. (Felipe F.); Amil, M. (María); Zulet, M.A. (María Ángeles); Carreira, M.C. (Marcos C.); Crujeiras, A.B. (Ana B.); Abete, I. (Itziar)The present research evaluated circulating betatrophin levels in obese patients with metabolic syndrome features under energy-restricted weight-loss programs and in normal weight in order to stablish the putative interplay between the levels of this hormone, diet and metabolic risk factors linked to obesity and associated comorbidities.
- Relationship of oxidized low density lipoprotein with lipid profile and oxidative stress markers in healthy young adults: a translational study(Biomed Central, 2011) Martinez, J.A. (José Alfredo); Hermsdorff, H.H. (H. H.); Barbosa, K.B. (K.B.); Zulet, M.A. (María Ángeles); Volp, A.C.P. (Ana Carolina P.); Navarro-Blasco, I. (Iñigo); Bressan, J. (J.)BACKGROUND: Despite oxidized low density lipoprotein (ox-LDL) plays important roles in the pro-inflammatory and atherosclerotic processes, the relationships with metabolic and oxidative stress biomarkers have been only scarcely investigated in young adult people. Thus, the aim of this study was to assess plasma ox-LDL concentrations and the potential association with oxidative stress markers as well as with anthropometric and metabolic features in healthy young adults. METHODS: This study enrolled 160 healthy subjects (92 women/68 men; 23±4 y; 22.0±2.9 kg/m2). Anthropometry, body composition, blood pressure, lifestyle features, biochemical data, and oxidative stress markers were assessed with validated tools. Selenium, copper, and zinc nail concentrations were measured by atomic absorption spectrophotometry. RESULTS: Total cholesterol (TC), LDL-c and uric acid concentrations, TC-to-HDL-c ratio, and glutathione peroxidase (GPx) activity were positive predictors of ox-LDL concentrations, while nail selenium level (NSL) was a negative predictor, independently of gender, age, smoking status, physical activity. Those individuals included in the highest tertile of GPx activity (≥611 nmol/[mL/min]) and of NSL (≥430 ng/g of nail) had higher and lower ox-LDL concentrations, respectively, independently of the same covariates plus truncal fat or body mass index, and total cholesterol or LDL-c concentrations. CONCLUSIONS: Ox-LDL concentrations were significantly associated with lipid biomarkers, GPx activity, uric acid concentration, and NSL, independently of different assayed covariates, in young healthy adults. These findings jointly suggest the early and complex relationship between lipid profile and redox status balance.
- Efecto del ácido linoleico conjugado (CLA) sobre el perfil lipídico en humanos(Sociedad Latinoamericana de Nutrición (SLAN), 2009) Martinez, J.A. (José Alfredo); Agueda, M. (Mayi); Zulet, M.A. (María Ángeles)El término ácido linoleico conjugado (CLA) hace referencia a un grupo de isómeros del ácido linoleico, caracterizados por tener enlaces dobles conjugados en varias posiciones y conformaciones. El CLA se encuentra de forma natural en algunos alimentos, aunque desde que se le atribuyen efectos beneficiosos sobre varios aspectos relacionados con la salud, numerosos grupos investigadores han estudiado los efectos de la suplementación con este ácido graso. En este sentido, el efecto del CLA sobre el perfil lipídico de los animales ha sido extensamente estudiado y existen evidencias confirmadas de beneficios sobre diversos marcadores metabólicos. Sin embargo, los resultados de los ensayos de intervención en humanos son ambiguos. El objetivo de esta revisión fue reunir los datos disponibles y más actuales acerca de los efectos del CLA en el perfil lipídico de humanos. Diversos estudios no hallaron efectos significativos en ninguna de las variables estudiadas; sin embargo, otros trabajos encontraron tanto efectos beneficiosos como desfavorables en el colesterol total, c-LDL, c-HDL, índice aterogénico, triglicéridos y lipoproteína(a). Esta discrepancia podría probablemente deberse a las diferencias en la dosis, composición de isómeros y placebo utilizado, así como a la duración del estudio y al estado nutricional de los sujetos incluidos, entre otros. No obstante, el análisis de los estudios de 12 semanas de duración, realizados con una mezcla en cantidades iguales de los dos isómeros principales del CLA (cis-9, trans-11 y trans-10, cis-12) y con dosis diarias de entre 3 y 4 g aproximadamente, parecen ofrecer los resultados más beneficiosos.
- Central adiposity rather than total adiposity measurements are specifically involved in the inflammatory status from healthy young adults.(Springer, 2011) Martinez, J.A. (José Alfredo); Hermsdorff, H.H. (H. H.); Zulet, M.A. (María Ángeles); Puchau, B. (Blanca)This study assessed the potential association of some proinflammatory markers with adiposity (total vs. central) and metabolic features in young adults. Measurements included body composition, lifestyle features, blood biochemical, and selected inflammatory indicators on 154 healthy subjects (53 M/101 F; 21.5 ± 3 years; 22.1 ± 2.6 kg/m(2)). Those subjects with higher waist circumference (WC) and waist-hip ratio (WHR) showed higher (P < 0.05) C-reactive protein (CRP), complement C3, interleukin-6 (IL6), and retinol binding protein-4 (RBP4) concentrations, while only IL6 was positively associated with total body fat (%). Furthermore, CRP and RBP4 were higher in former/current smokers, as compared to never smokers (P < 0.05). Some indicators of glucose (homeostasis model assessment-insulin resistance) and lipid metabolism (total cholesterol/high density lipoprotein-cholesterol and triglycerides) were positively associated with the assayed inflammatory markers (P < 0.05). The findings of this cross-sectional study indicate that central adiposity-related indicators (WC/WHR) correlated better than those assessing total adiposity with plasma proinflammatory markers, which additionally were associated with lifestyle and metabolic features in healthy young adults.