Abstract The prevalence of metabolic syndrome (MetS) manifestations is rapidly increasing worldwide, and is becoming an important health problem. Actually, MetS includes a combination of clinical ...complications such as obesity (central adiposity), insulin resistance, glucose intolerance, dyslipidemia, non-alcoholic fatty liver disease and hypertension. All these alterations predispose individuals to type 2 diabetes and cardiovascular disease inducing earlier mortality rates among people. In general terms, it is difficult for patients to follow a standard long-term diet/exercise regime that would improve or alleviate MetS symptoms. Thus, the investigation of food components that may deal with the MetS features is an important field for ameliorate and facilitate MetS dietary-based therapies. Currently antioxidants are of great interest due to the described association between obesity, cardiovascular alterations and oxidative stress. On the other hand, high MUFA and PUFA diets are being also considered due to their potential benefits on hypertension, insulin resistance and triglyceride levels. Mineral composition of the diet is also relevant since high potassium intake may improve hypertension and high calcium consumption may promote lipid oxidation. Thus, although nutritional supplements are at the peak of dietetic therapies, the consumption of some specific foods (legumes, fatty fish, vegetables and fruits, etc) with bioactive components within an energy-restricted diet is a promising approach to manage MetS manifestations. Therefore, the present review focuses on some of the most important food components currently investigated to improve and make easier the nutritional MetS treatment.
The understanding of the potential role of betatrophin in human metabolic disorders is a current challenge.
The present research evaluated circulating betatrophin levels in obese patients with ...metabolic syndrome (MetSyn) features under energy-restricted weight-loss programs and in normal weight in order to establish the putative interplay between the levels of this hormone, diet and metabolic risk factors linked to obesity and associated comorbidities.
One hundred forty-three participants were enrolled in the study (95 obese-MetSyn; age 49.5±9.4 years; body mass index (BMI) 35.7±4.5 kg m(-2) and 48 normal weight; age 35.71±8.8 years; BMI 22.9±2.2 kg m(-2)). A nutritional therapy consisting in two hypocaloric strategies (control diet based on the AHA recommendations and the RESMENA (MEtabolic Syndrome REduction in Navarra) diet, a novel dietary program with changes in the macronutrient distribution) was only prescribed to obese-MetSyn participants who were randomly allocated to the dietary strategies. Dietary records, anthropometrical and biochemical variables as well as betatrophin levels were analyzed before (pre-intervention, week 0), at 8 weeks (post-intervention, week 8) and after 4 additional months of self-control period (follow-up, week 24).
Betatrophin levels were higher in obese-MetSyn patients than normal-weight subjects (1.24±0.43 vs 0.97±0.69 ng ml(-1), respectively, P=0.012), and levels were positively associated with body composition, metabolic parameters, leptin and irisin in all participants at baseline. Notably, low pre-intervention (week 0) betatrophin levels in obese patients were significantly associated with higher dietary-induced changes in atherogenic risk factors after 8 weeks. Moreover, protein intake, especially proteins from animal sources, was an independent determinant of betatrophin levels after dietary treatment (B=-0.27; P=0.012).
Betatrophin is elevated in obese patients with MetSyn features and is associated with poorer nutritional outcomes of adiposity and dyslipidemia traits after a weight-loss program. Dietary protein intake could be a relevant modulator of betatrophin secretion and activity.
Abstract Background and aims Cocoa flavanols are recognised by their favourable antioxidant and vascular effects. This study investigates the influence on health of the daily consumption of ...ready-to-eat meals supplemented with cocoa extract within a hypocaloric diet, on middle-aged overweight/obese subjects. Methods and results Fifty healthy male and female middle-aged volunteers 57.26 ± 5.24 years and body mass index (BMI) 30.59 ± 2.33 kg/m2 were recruited to participate in a 4 week randomised, parallel and double-blind study. After following 3 days on a low-polyphenol diet, 25 volunteers received meals supplemented with 1.4 g of cocoa extract (645.3 mg of polyphenols) and the other 25 participants received control meals, within a 15% energy restriction diet. On the 4th week of intervention individuals in both dietary groups improved ( p < 0.05) anthropometric, body composition, blood pressure and blood biochemical measurements. Oxidised LDL cholesterol (oxLDL), showed a higher reduction ( p = 0.030) in the cocoa group. Moreover, myeloperoxidase (MPO) levels decreased only in the cocoa supplemented group ( p = 0.007). Intercellular Adhesion Molecule-1 (sICAM-1) decreased significantly in both groups, while Vascular Cell Adhesion Molecule-1 (sVCAM-1) did not present differences after the 4 weeks of intervention. Interestingly, cocoa intake showed a different effect by gender, presenting more beneficial effects in men. Conclusions The consumption of cocoa extract as part of ready-to-eat meals and within a hypocaloric diet improved oxidative status (oxLDL) in middle-aged subjects, being most remarkable in males. Registration number: Registered at www.clinicaltrials.gov ( NCT01596309 ).
Introduction
Dopamine (DA) is a neurotransmitter that regulates the rewarding and motivational processes underlying food intake and eating behaviors. This study hypothesized associations of DNA ...methylation signatures at genes modulating DA signaling with obesity features, metabolic profiles, and dietary intake.
Methods
An adult population within the Methyl Epigenome Network Association project was included (n = 473). DNA methylation levels in white blood cells were measured by microarray (450K). Differentially methylated genes were mapped within the dopaminergic synapse pathway using the KEGG reference database (map04728). Subsequently, network enrichment analyses were run in the pathDIP portal. Associations of methylation patterns with anthropometric markers of general (BMI) and abdominal obesity (waist circumference), the blood metabolic profile, and daily dietary intakes were screened.
Results
After applying a correction for multiple comparisons, 12 CpG sites were strongly associated (p < 0.0001) with BMI: cg03489495 (ITPR3), cg22851378 (PPP2R2D), cg04021127 (PPP2R2D), cg22441882 (SLC18A1), cg03045635 (DRD5), cg23341970 (ITPR2), cg13051970 (DDC), cg08943004 (SLC6A3), cg20557710 (CACNA1C), cg24085522 (GNAL), cg16846691 (ITPR2), and cg09691393 (SLC6A3). Moreover, average methylation levels of these genes differed according to the presence or absence of abdominal obesity. Pathway analyses revealed a statistically significant contribution of the aforementioned genes to dopaminergic synapse transmission (p = 4.78E−08). Furthermore, SLC18A1 and SLC6A3 gene methylation signatures correlated with total energy (p < 0.001) and carbohydrate (p < 0.001) intakes.
Conclusions
The results of this investigation reveal that methylation status on DA signaling genes may underlie epigenetic mechanisms contributing to carbohydrate and calorie consumption and fat deposition.
This study hypothesized associations of DNA methylation signatures at genes modulating DA signaling with obesity features, metabolic profiles, and dietary intake. The results of this investigation reveal that methylation status on DA signaling genes may underlie epigenetic mechanisms contributing to carbohydrate and calorie consumption and fat deposition.
The aim of this study was to investigate the potential benefits of an extract obtained from seeds/fruits of an Oleaceae (Fraxinus excelsior L.) on glucose homeostasis and associated metabolic markers ...in non-diabetic overweight/obese subjects.
This study was performed in 22 participants (50–80 years-old; BMI 31.0kg/m2). The design was a longitudinal, randomized, crossover, double-blind, placebo-controlled 7-week nutritional intervention. The participants received daily 3 capsules each containing either 333mg of an extract from Fraxinus excelsior L. seeds (Glucevia®) or placebo capsules (control) in a random order for 3 weeks with 1 week of washout between treatments. Moreover, they followed a balanced covert energy-restricted diet (−15% energy). All variables were measured at the beginning and at the end of each period.
Compared to baseline, the administration of 1g of Glucevia® for 3 weeks resulted in significantly lower incremental glucose area under the curve (−28.2%; p<0.01), and significantly lower 2h blood glucose values (−14%; p<0.01) following an oral glucose tolerance test. No significant changes were found in the control group (−7.9% AUC, −1.6% 2h blood glucose). Furthermore, significant differences were found between responses in the control and Glucevia® groups with respect to serum fructosamine and plasma glucagon levels (p<0.01 and p<0.05, respectively). Interestingly, administration of Glucevia® significantly increased the adiponectin:leptin ratio (p<0.05) and decreased fat mass (p<0.01) compared to control (p<0.05).
The administration of an extract from Fraxinus excelsior L. seeds/fruits in combination with a moderate hypocaloric diet may be beneficial in metabolic disturbances linked to impaired glucose tolerance, obesity, insulin resistance and inflammatory status, specifically in older adults.
Background
Leptin and ghrelin appear to play a role in weight regain after a successful weight loss. The pre-treatment plasma levels of leptin/ghrelin ratio (L/G) could have power to predict this ...clinically relevant issue in the obesity treatment.
Objective
To evaluate the ability of the L/G as a non-invasive tool for the early discrimination of obese patients who are more likely to regain weight after an energy restriction program (regainers) from those who maintain the lost weight (non-regainers).
Subjects and methods
Fasting leptin and ghrelin levels were evaluated in 88 overweight/obese patients who followed an 8-week hypocaloric diet program and were categorized as regainers (≥10 % weight-lost regain) and non-regainers (<10 % weight-lost regain) 6 months (32 weeks) after finishing the dietary treatment. A receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic value of the L/G ratio and to establish a cut-off point to differentiate regainers from non-regainers.
Results
Regainers showed a statistically higher baseline (week 0) and after treatment (week 8) L/G ratio than non-regainers. The baseline L/G ratio was associated with an increased risk for weight regain (odds ratio 1.051;
p
= 0.008). Using the area under the ROC curve (AUC), the L/G ratio significantly identified female (AUC = 0.69;
p
= 0.040) and male regainers (AUC = 0.68;
p
= 0.030). The maximum combination of sensitivity and specificity was shown at the cut-off point of 26.0 for women and 9.5 for men.
Conclusions
The pre-intervention fasting leptin/ghrelin ratio could be a useful non-invasive approach to personalize obesity therapy and avoid unsuccessful treatment outcomes.
Some causal bases of stroke remain unclear, but the nutritional effects on the epigenetic regulation of different genes may be involved. The aim was to assess the impact of epigenetic processes of ...human tumor necrosis factor (TNF-α) and paraoxonase (PON) promoters in the susceptibility to stroke when considering body composition and dietary intake. Twenty-four patients (12 non-stroke/12 stroke) were matched by sex (12 male/12 female), age (mean 70 ± 12 years old), and BMI (12 normal-weight/12 obese; mean 28.1 ± 6.7 kg/m
2
). Blood cell DNA was isolated and DNA methylation levels of TNF-α (−186 to +349 bp) and PON (−231 to +250 bp) promoters were analyzed by the Sequenom EpiTYPER approach. Histone modifications (H3K9ac and H3K4me3) were analyzed also by chromatin immunoprecipitation in a region of TNF-α (−297 to −185). Total TNF-α promoter methylation was lower in stroke patients (
p
< 0.001) and showed no interaction with body composition (
p
= 0.807). TNF-α and PON total methylation levels correlated each other (
r
= 0.44;
p
= 0.031), especially in stroke patients (
r
= 0.72;
p
= 0.008). The +309 CpG methylation site from TNF-α promoter was related to body weight (
p
= 0.027) and the region containing three CpGs (from −170 to −162 bp) to the percentage of lipid intake and dietary indexes (
p
< 0.05) in non-stroke patients. The methylation of PON +15 and +241 CpGs was related to body weight (
p
= 0.021), waist circumference (
p
= 0.020), and energy intake (
p
= 0.018), whereas +214 was associated to the quality of the diet (
p
< 0.05) in non-stroke patients. When comparing stroke vs non-stroke patients regarding the histone modifications analyzed at TNF-α promoter, no changes were found, although a significant association was identified between circulating TNF-α level and H3K9ac with H3K4me3. TNF-α and PON promoter methylation levels could be involved in the susceptibility to stroke and obesity outcome, respectively. The dietary intake and body composition may influence this epigenetic regulation in non-stroke patients.
The high prevalence of metabolic syndrome (MS) in Spain requires additional efforts for prevention and treatment.
The study RESMENA-S aims to improve clinical criteria and biomarkers associated with ...MS though an integral therapy approach.
The study is a randomized prospective parallel design in which is expected to participate a total of 100 individuals. The RESMENA-S group (n = 50) is a personalized weight loss (30% energy restriction) diet, with a macronutrient distribution (carbohydrate / fat / protein) of 40/30/30, high meal frequency (7 / day), low glycemic index/load and high antioxidant capacity as well as a high adherence to the Mediterranean diet. The control group (n = 50) is assigned to a diet with the same energy restriction and based on the American Heart Association pattern. Both experimental groups are under dietary and psychological control during 8 weeks. Likewise, for an additional period of 16 weeks of self-control, is expected that volunteers will follow the same pattern but with no dietary advice.
Anthropometrical data and body composition determinations as well as blood and urine samples are being collected at the beginning and end of each phase. This project is registered at www.clinicaltrials.gov with the number NCT01087086 and count with the Research Ethics Committee of the University of Navarra approval (065/2009).
Intervention trials to promote the adoption of dietary patterns and healthy lifestyle are of great importance to identify the outcomes and nutritional mechanisms that might explain the link between obesity, metabolic syndrome and associated complications.
Adiponectin is an adipose tissue-specific hormone that is commonly decreased in obese subjects. Furthermore, single-nucleotide polymorphisms (SNPs) of the adiponectin gene have been associated with ...metabolic phenotypes. The present study investigated whether the adiponectin gene promoter variant -11391 G/A (rs17300539) could predict the risk of developing traits characterizing the metabolic syndrome (MetS) and the impact of weight management. The -11391 G/A SNP was genotyped in 180 Spanish volunteers (BMI: 31.4+/-3.2 kg/m (2); age: 35+/-5 years). Clinical measurements were determined at baseline, following an 8-week low-calorie diet (LCD), and at 32 and 60 weeks. At baseline, the GG genotype was associated with higher HOMA-IR, insulin and triacylglyceride concentrations than other genotypes (p<0.05) and was also related with a higher risk of insulin resistance (OR: 2.437, p=0.025) and MetS clinical manifestations (OR: 3.236, p=0.003). Following the LCD, the increased risk in GG subjects compared with others disappeared (p>0.05). By 32 weeks after dietary therapy (n=84), GG carriers had recovered the risk of metabolic comorbidities (OR: 2.420, p=0.043). This risk was even more evident after 60 weeks (OR: 2.875, p=0.014). These data show an increased risk of insulin resistance and MetS complications in obese subjects of the -11391 GG genotype. The risk was markedly reduced during an energy-restricted diet, but was not sustained. Carriage of the A allele therefore confers protection from weight regain, and the effect is particularly evident 32-60 weeks after the dietary intervention, when improvement in GG subjects had disappeared.
Nutritional strategies to treat obesity often influence neuroendocrine factors related to body weight control. The present study aimed to investigate whether the inclusion of three fatty fish ...servings per week within a hypocaloric diet may have specific healthy effects on insulin and leptin functions. Thirty-two subjects (body mass index = 31.6 ± 3.5 kg m⁻²) aged 36 ± 7 years, were assigned to a control or fish-based energy-restricted diet over an 8-week period. Anthropometry, body composition, lipid profile, leptin and insulin values were measured at the start and at the end of the dietary intervention. Both experimental diets resulted in a similar mean weight loss (control = 5.3 ± 2.6% versus fish-based = 5.5 ± 2.5%; P = 0.783). A significant reduction in insulin resistance, as determined by the homeostatic model assessment index (HOMA-IR = insulin x glucose/22.5), was observed after the fish-based intervention. The change in circulating leptin was higher in the fish-based diet compared to the control group. Sixteen percent of the variability in the change of adjusted-leptin could be explained (P = 0.034) by the HOMA index change and the type of diet. Three servings a week of fatty fish included in an energy-restricted diet appears to be a valid strategy for specifically improving insulin sensitivity and leptin levels in obese subjects, which could involve a better body weight regulation after a nutritional intervention period.
PDF
