María Ángeles Zulet

Obesity and the metabolic syndrome: role of different dietary macronutrient distribution patterns and specific nutritional components on weight loss and maintenance

Weight loss and subsequent body weight maintenance are difficult for obese individuals despite the wide variety of dietary regimens and approaches. A substantial body of scientific evidence has shown that by simply varying the macronutrient distribution and composition of dietary factors, weight losses of varying amounts, longer-term body weight maintenance periods, better appetite regulation, and changes in features of the metabolic syndrome can be achieved. At present, renewed efforts are underway to increase the protein content of weight-loss diets, simultaneously restrict fat consumption to no more than 30%, favor polyunsaturated fat, have carbohydrates account for between 40 and 50% of total energy intake, and promote the consumption of low-glycemic foods. The present article reviews the scientific evidence for the effects of several dietary manipulations and sustainable strategies for weight loss and body weight stability as well as for treating specific features of the metabolic syndrome.

A dual epigenomic approach for the search of obesity biomarkers: DNA methylation in relation to diet-induced weight loss

Epigenetics could help to explain individual differences in weight loss after an energy‐restriction intervention. Here, we identify novel potential epigenetic biomarkers of weight loss, comparing DNA methylation patterns of high and low responders to a hypocaloric diet. Twenty‐five overweight or obese men participated in an 8‐wk caloric restriction intervention. DNA was isolated from peripheral blood mononuclear cells and treated with bisulfite. The basal and endpoint epigenetic differences between high and low responders were analyzed by methylation microarray, which was also useful in comparing epigenetic changes due to the nutrition intervention. Subsequently, MALDI‐TOF mass spectrometry was used to validate several relevant CpGs and the surrounding regions. DNA methylation levels in several CpGs located in the ATP10A and CD44 genes showed statistical baseline differences depending on the weight‐loss outcome. At the treatment endpoint, DNA methylation levels of several CpGs on the WT1 promoter were statistically more methylated in the high than in the low responders. Finally, different CpG sites from WT1 and ATP10A were significantly modified as a result of the intervention. In summary, hypocaloricdiet‐induced weight loss in humans could alter DNA methylation status of specific genes. Moreover, baseline DNA methylation patterns may be used as epigenetic markers that could help to predict weight loss.—Milagro, F. I., Campion, J., Cordero, P., Goyenechea, E., Gómez‐Uriz, A. M., Abete, I., Zulet, M. A., Martínez, J. A. A dual epigenomic approach for the search of obesity biomarkers: DNA methylation in relation to diet‐induced weight loss. FASEB J. 25, 1378–1389 (2011). www.fasebj.org

Fruit and vegetable consumption and proinflammatory gene expression from peripheral blood mononuclear cells in young adults: a translational study

BackgroundFruits and vegetables are important sources of fiber and nutrients with a recognized antioxidant capacity, which could have beneficial effects on the proinflammatory status as well as some metabolic syndrome and cardiovascular disease features. The current study assessed the potential relationships of fruit and vegetable consumption with the plasma concentrations and mRNA expression values of some proinflammatory markers in young adults.MethodsOne-hundred and twenty healthy subjects (50 men/70 women; 20.8 ± 2.6 y; 22.3 ± 2.8 kg/m2) were enrolled. Experimental determinations included anthropometry, blood pressure and lifestyle features as well as blood biochemical and inflammatory measurements. The mRNA was isolated from peripheral blood mononuclear cells (PBMC) and the gene expression concerning selected inflammatory markers was assessed by quantitative real-time PCR. Nutritional intakes were estimated by a validated semi-quantitative food-frequency questionnaire.ResultsThe highest tertile of energy-adjusted fruit and vegetable consumption (>660 g/d) was associated with lower plasma concentrations of C-reactive protein (CRP) and homocysteine and with lower ICAM1, IL1R1, IL6, TNFα and NFκB1 gene expression in PBMC (P for trend < 0.05), independently of gender, age, energy intake, physical activity, smoking, body mass index, systolic blood pressure and circulating non-esterified fatty acids. In addition, plasma CRP, homocysteine and TNFα concentrations and ICAM1, TNFα and NFκB1 gene expression in PBMC showed a descending trend as increased fiber intake (>19.5 g/d) from fruits and vegetables (P for trend < 0.05). Furthermore, the participants within the higher tertile (>11.8 mmol/d) of dietary total antioxidant capacity showed lower plasma CRP and mRNA values of ICAM1, IL1R1, IL6, TNFα and NFκB1 genes (P for trend < 0.05). The inverse association between fruit and vegetable consumption and study proinflammatory markers followed the same trend and remained statistically significant, after the inclusion of other foods/nutrients in the linear regression models.ConclusionA higher fruit and vegetable consumption was independently associated not only with reduced CRP and homocysteine concentrations but also with a lower mRNA expression in PBMC of some relevant proinflammatory markers in healthy young adults.

Vitamin C and fibre consumption from fruits and vegetables improves oxidative stress markers in healthy young adults.

The aim of the present cross-sectional study was to assess the potential relationships between fruit and vegetable (FV) consumption and some oxidative stress markers in young adults, with particular emphasis on fibre and vitamin C intake. The study enrolled 246 healthy subjects (eighty-eight men and 158 women), with a mean age of 22 (sd 3) years and a mean BMI of 21·9 (sd 2·8) kg/m2. Dietary intake, anthropometry, blood pressure, lifestyle features and blood biochemical data were assessed with validated procedures. Those subjects in the highest tertile (T) of FV consumption ( ≥ 705 g/d) had statistically lower oxidised LDL (ox-LDL) concentrations as well as higher plasma total antioxidant capacity (TAC) and glutathione peroxidase (GPx) activity (P for trend <0·05), after adjusting for sex, age, energy intake, physical activity, smoking, BMI, vitamin supplement use and other confounding factors. Moreover, plasma ox-LDL concentrations showed a decreasing trend and TAC an increasing trend across tertiles of fibre (T3: ≥14 g/d) and vitamin C (T3: ≥150 mg/d) from FV intake, while GPx activity was positively associated with vitamin C intake (P for trend < 0·05). In conclusion, greater FV consumption was independently associated with reduced ox-LDL as well as increased TAC and GPx activity in healthy young adults, with dietary fibre and vitamin C from FV clearly being implicated in this beneficial relationship.

Association of Body Fat Distribution with Proinflammatory Gene Expression in Peripheral Blood Mononuclear Cells from Young Adult Subjects

Peripheral blood mononuclear cells (PBMC) measurements have proved useful in recent studies to discern peripheral biomarkers for common complex diseases and for understanding host responses to drugs and nutrition in personalized medicine. Despite the initial promising data from PBMC, there is little information, however, on inflammatory and immune gene regulation in the context of body fat distribution and metabolic features in healthy adults. We investigated the putative association of body fat distribution and related-metabolic features with mRNA levels of proinflammatory markers in PBMC. This study enrolled 136 healthy subjects (85 females/51 males; age: 21.5 +/- 2.5 years). Anthropometrical, clinical, metabolic, and proinflammatory variables were assessed with validated tools. Interestingly, in normal-weight subjects with lower truncal fat (TF) values, mRNA levels of ICAM1, IL1R1, IL6, and TNF-alpha in PBMC were lower (p < 0.05), compared to normal-weight individuals with higher TF (>58.5/50.2% for men/women, respectively) and overweight/obese subjects [body mass index (BMI) >25 kg/m(2)]. After regression analyses were performed, individuals with the highest tertiles of TF and waist circumference displayed higher mRNA gene expressions as well as circulating proinflammatory (C-reactive protein and IL6) and metabolic (blood pressure, HOMA-IR, and LDL-c:HDL-c ratio) variables values (p < 0.05), independent from gender. Our findings collectively suggest that the mRNA expression of certain proinflammatory markers in PBMC is associated with body fat distribution in healthy adult subjects, which in turn, was also related to metabolic features and plasma proinflammatory markers concentrations.

Plasma irisin depletion under energy restriction is associated with improvements in lipid profile in metabolic syndrome patients.

A recently discovered myokine, irisin, may have an important role in energy metabolism. This study aimed to evaluate the relationship between this hormone and the lipid profile of patients with metabolic syndrome (MetS) following a hypocaloric diet.

Hypothesis-oriented food patterns and incidence of hypertension: 6-year follow-up of the SUN (Seguimiento Universidad de Navarra) prospective cohort.

OBJECTIVE To study the association between adherence to several a priori-defined healthy food patterns and the risk of hypertension. DESIGN Prospective, multipurpose, dynamic cohort study (recruitment permanently open). We followed up 10 800 men and women (all of them university graduates), who were initially free of hypertension, for a variable period (range 2-6 years, median 4.6 years). During follow-up, 640 participants reported a new medical diagnosis of hypertension. Baseline diet was assessed using a validated 136-item FFQ. Validated information about non-dietary potential confounders was also gathered. We calculated adherence to fifteen different hypothesis-oriented food patterns and assessed the association between each of them and incident hypertension using multivariable Cox models. SETTING The SUN (Seguimiento Universidad de Navarra - University of Navarra Follow-up) Project, Spain. SUBJECTS Participants recruited to the SUN cohort before October 2005 were eligible for inclusion; after excluding those with self-reported hypertension or CVD at baseline, or with extreme total energy intake, data of 10 800 were analysed. RESULTS Higher adherence to the DASH (Dietary Approaches to Stop Hypertension) diet (range of the score: 0 to 5) was significantly associated with a lower risk for developing hypertension (P for trend = 0.02). The other food patterns showed no significant association with incident hypertension. CONCLUSIONS Our results support a long-term protection of the DASH diet against the incidence of hypertension, but we found no evidence of a similar inverse association with hypertension for any other a priori-defined healthy food pattern.

The Influence of Mediterranean, Carbohydrate and High Protein Diets on Gut Microbiota Composition in the Treatment of Obesity and Associated Inflammatory State

The role of the gut microbiota in understanding the onset and development of obesity is gaining importance. Dietary strategies are the main tool employed to counteract obesity, and nowadays they are focused on a wide range of different aspects of diet and not only on calorie restriction. Additionally, diet is known to be a major factor influencing modification of the gut microbiota. Therefore the influence of both macronutrient and micronutrient content of any dietary strategy to treat obesity on gut bacterial composition should now be taken into consideration, in addition to energy restriction. This review aims to collect the available data regarding the influence of different dietary components on gut microbiota in relation to obesity and inflammatory states in humans. Although more work is needed, specific dietary factors (carbohydrate, protein and Mediterranean foods) have been shown to have an influence on the gut microbiome composition, meaning that there is an opportunity to prevent and treat obesity based on microbiota outcomes.

Hormonal and inflammatory impact of different dietetic composition: emphasis on dietary patterns and specific dietary factors

Healthy dietary pattern, characterized by the consumption of fruits, vegetables, white meats, skim dairy products, nuts and moderate intake of vegetable oils and alcohol, is an important factor for a lower risk of chronic disease such as obesity, metabolic syndrome and cardiovascular disease. This beneficial effect can be explained, at least partially, by its modulating role on biomarkers of insulin sensitivity and atherosclerosis as well as of inflammation and endothelial function. On the other hand, the intake of specific dietary factors, such as unsaturated fatty acids (oleic and alpha-linolenic) and micronutrients with antioxidant properties (vitamins A, E and C; selenium, zinc) has been discussed, due to its potential protector action due to chronic disease occurrence and its possible profits in hormonal, metabolic and inflammatory regulations that these dietetic factors can provide within a nutritional treatment to obesity and metabolic syndrome.

Expression of inflammation-related miRNAs in white blood cells from subjects with metabolic syndrome after 8 wk of following a Mediterranean diet-based weight loss program

OBJECTIVES The aim of this study was to evaluate the influence of a dietary strategy for weight loss (the RESMENA [reduction of metabolic syndrome in Navarra, Spain] diet) on the expression of inflammation-related microRNAS (miRNAs) and genes in white blood cells (WBC) from individuals with metabolic syndrome (MetS). METHODS The clinical, anthropometric, and biochemical characteristics of 40 individuals with MetS (20 men and 20 women; age: 48.84 ± 10.02 y; body mass index: 35.41 ± 4.42 kg/m(2)) were evaluated before and after an 8-wk hypocaloric diet based on the Mediterranean dietary pattern. Nutrient intake was assessed with a food frequency questionnaire and 48-h weighed food records. Total RNA was isolated from WBC and the expression of some inflammation-related miRNAs and mRNAs (IL-6, TNF-α, ICAM-1, IL-18, SERPINE1, VCAM-1, GAPDH) was assessed by quantitative polymerase chain reaction. RESULTS The RESMENA nutritional intervention improved most anthropometric and biochemical features. The expression of miR-155-3p was decreased in WBC, whereas Let-7b was strongly upregulated as a consequence of the dietary treatment. However, they were not correlated with the expression of the proinflammatory genes in the same cells. The changes in the expression of let-7b, miR-125b, miR-130a, miR-132-3p, and miR-422b were significantly associated with changes in diet quality when assessed by the Healthy Eating Index. Moreover, low consumption of lipids and saturated fat (g/d) were associated with higher expression of let-7b after the nutritional intervention. CONCLUSIONS The Mediterranean-based nutritional intervention was able to induce changes in the expression of let-7b and miR-155-3p in WBC from patients with MetS after 8 wk. Moreover, the quality of the diet has an important effect on the miRNAs expression changes. These results should be highlighted because these miRNAs have been associated with inflammatory gene regulation and important human diseases.