Methylation profile of the ADRB3 gene and its association with lipid profile and nutritional status in adults.

BACKGROUND: Defects in DNA methylation have been shown to be associated with metabolic diseases such as obesity, dyslipidemia, and hypercholesterolemia. To analyze the methylation profile of the ADRB3 gene and correlate it with lipid profile, lipid intake, and oxidative stress based on malondialdehyde (MDA) and total antioxidant capacity (TAC), homocysteine and folic acid levels, nutritional status, lifestyle, and socioeconomic variables in an adult population. A cross-sectional epidemiological study representative of the East and West regions of the municipality of João Pessoa, Paraíba state, Brazil, enrolled 265 adults of both genders. Demographic, lifestyle, and socioeconomic questionnaires and a 24-h recall questionnaire were applied by trained interviewers' home. Nutritional and biochemical evaluation (DNA methylation, lipid profile, MDA, TAC, homocysteine and folic acid levels) was performed. RESULTS: DNA hypermethylation of the ADRB3 gene, analyzed in leukocytes, was present in 50% of subjects and was associated with a higher risk of being overweight (OR 3.28; p = 0.008) or obese (OR 3.06; p = 0.017), a higher waist-hip ratio in males (OR 1.17; p = 0.000), greater intake of trans fats (OR 1.94; p = 0.032), higher LDL (OR 2.64; p = 0.003) and triglycerides (OR 1.81; p = 0.031), and higher folic acid levels (OR 1.85; p = 0.022). CONCLUSIONS: These results suggest that epigenetic changes in the ADRB3 gene locus may explain the development of obesity and non-communicable diseases associated with trans-fat intake, altered lipid profile, and elevated folic acid. Because of its persistence, DNA methylation may have an impact in adults, in association with the development of non-communicable diseases. This study is the first population-based study of the ADRB3 gene, and the data further support evaluation of ADRB3 DNA methylation as an effective biomarker.

Decrease of the DNA methylation levels of the ADRB3 gene in leukocytes is related with serum folate in eutrophic adults.

BACKGROUND: DNA methylation has been evidenced as a potential epigenetic mechanism related to various candidate genes to development of obesity. Therefore, the objective of this study was to evaluate the DNA methylation levels of the ADRB3 gene by body mass index (BMI) in a representative adult population, besides characterizing this population as to the lipid profile, oxidative stress and food intake. METHODS: This was a cross-sectional population-based study, involving 262 adults aged 20-59 years, of both genders, representative of the East and West regions of the municipality of João Pessoa, Paraíba state, Brazil, in that were evaluated lifestyle variables and performed nutritional, biochemical evaluation and DNA methylation levels of the ADRB3 gene using high resolution melting method. The relationship between the study variables was performed using analyses of variance and multiple regression models. All results were obtained using the software R, 3.3.2. RESULTS: From the stratification of categories BMI, was observed a difference in the average variables values of age, waist-to-height ratio, waist-to-hip ratio, waist circumference, triglycerides and intake of trans fat, which occurred more frequently between the categories "eutrophic" and "obesity". From the multiple regression analysis in the group of eutrophic adults, it was observed a negative relationship between methylation levels of the ADRB3 gene with serum levels of folic acid. However, no significant relation was observed among lipid profile, oxidative stress and food intake in individuals distributed in the three categories of BMI. CONCLUSIONS: A negative relationship was demonstrated between methylation levels of the ADRB3 gene in eutrophic adults individuals with serum levels of folic acid, as well as with the independent gender of BMI, however, was not observed relation with lipid profile, oxidative stress and variables of food intake. Regarding the absence of relationship with methylation levels of the ADRB3 gene in the categories of overweight, mild and moderate obesity, the answer probably lies in the insufficient amount of body fat to initiate inflammatory processes and oxidative stress with a direct impact on methylation levels, what is differently is found most of the times in exacerbated levels in severe obesity.

Influence of the C677T Polymorphism of the MTHFR Gene on Oxidative Stress in Women With Overweight or Obesity: Response to a Dietary Folate Intervention.

The C677T polymorphism of the methylenetetrahydrofolate reductase gene (MTHFR) is related to folate metabolism and can alter the levels of biochemical markers.Objective: Investigate the influence of the MTHFR C677T polymorphism on the effects of a dietary folate intervention on oxidative stress in women with overweight or obesity.Methods: Forty-eight adult women with overweight or obesity were subjected to a 24-hour dietary recall, anthropometric measurements, biochemical analysis, and genotyping of the MTHFR C677T polymorphism. They were allocated by convenience sampling to 2 groups, which received 300 g of folate-rich vegetables containing 191 µg/d (Group 1) (n = 24) or 95 µg/d (Group 2) (n = 24) of folate for 8 weeks.Results: The dietary intervention increased the serum folic acid levels in the 2 analyzed groups. The intervention with 191 µg/d of folate led to relevant results in terms of homocysteine levels (p = 0.0005) and total antioxidant capacity (p = 0.0261); the effect was larger among carriers of the TT genotype.Conclusions: The study demonstrated the beneficial effect of folate intake in terms of a TAC elevation for the CC and TT genotypes of the MTHFR C677T polymorphism, an increase in folic acid levels for all genotypes, and a reduction in the Hcy levels for the TT genotype in response to an intervention consisting of an intake of 191 µg/d of folate supplied by vegetables.

Association between obesity and calcium:phosphorus ratio in the habitual diets of adults in a city of Northeastern Brazil: an epidemiological study.

BACKGROUND: Low calcium:phosphorus ratios (Ca:P ratio) in habitual diet have been observed worldwide, and it has been shown to be harmful to the bone health of the population. However, no study associating this ratio with obesity was found. Thus, considering that the intake of calcium and phosphorus will generate a ratio between them, which may be associated with obesity, this research seeks at evaluating the relation between obesity and the Ca:P ratio in the habitual diet of adults. METHODS: Cross-sectional population-based epidemiological study with stratified and systematic sampling. The sample was composed of 506 adults, aged between 18 and 60 years, of both genders. Information on socioeconomic and demographic conditions was obtained through questionnaires completed during home visits, where anthropometric and dietary evaluations were also conducted. RESULTS: In the habitual diet consumed by the study subjects, a Ca:P ratio above the median of 0.57 reduced the risk of central obesity based on waist-to-height ratio (WHtR) (OR: 0.61; 95% CI: 0.41 - 0.92). Habitual dietary intake of calcium (OR: 0.65; 95% CI: 0.43 - 0.97) and dairy products (OR: 0.56; 95% CI: 0.37 - 0.84) above the median value (485.4 mg and 0.9 servings, respectively) was found to be a protective factor related to central obesity based on WHtR. CONCLUSIONS: Values above the median for the Ca:P ratio found in the habitual diet were negatively associated with central obesity based on WHtR. In addition, calcium and dairy consumption were negatively associated with central obesity based on WHtR. Therefore, higher Ca:P ratios contributed to a lower prevalence of central obesity.

Short-term exposure to air pollution (PM2.5) induces hypothalamic inflammation, and long-term leads to leptin resistance and obesity via Tlr4/Ikbke in mice.

A previous study demonstrated that a high-fat diet (HFD), administered for one-three-days, induces hypothalamic inflammation before obesity's established, and the long term affects leptin signaling/action due to inflammation. We investigate whether exposure to particulate matter of a diameter of ≤2.5 µm (PM2.5) in mice fed with a chow diet leads to similar metabolic effects caused by high-fat feeding. Compared to the filtered air group (FA), one-day-exposure-PM2.5 did not affect adiposity. However, five-days-exposure-PM2.5 increased hypothalamic microglia density, toll-like-receptor-4 (Tlr4), and the inhibitor-NF-kappa-B-kinase-epsilon (Ikbke) expression. Concurrently, fat mass, food intake (FI), and ucp1 expression in brown adipose tissue were also increased. Besides, decreased hypothalamic STAT3-phosphorylation and Pomc expression were found after twelve-weeks-exposure-PM2.5. These were accompanied by increased FI and lower energy expenditure (EE), leading to obesity, along with increased leptin and insulin levels and HOMA. Mechanistically, the deletion of Tlr4 or knockdown of the Ikbke gene in the hypothalamus was sufficient to reverse the metabolic outcomes of twelve-weeks-exposure-PM2.5. These data demonstrated that short-term exposure-PM2.5 increases hypothalamic inflammation, similar to a HFD. Long-term exposure-PM2.5 is even worse, leading to leptin resistance, hyperphagia, and decreased EE. These effects are most likely due to chronic hypothalamic inflammation, which is regulated by Tlr4 and Ikbke signaling.

The direct correlation between oxidative stress and LDL-C levels in adults is maintained by the Friedewald and Martin equations, but the methylation levels in the MTHFR and ADRB3 genes differ.

Low-density lipoprotein (LDL-C) concentrations are a standard of care in the prevention of cardiovascular disease and are influenced by different factors. This study compared the LDL-C concentrations estimated by two different equations and determined their associations with inflammatory status, oxidative stress, anthropometric variables, food intake and DNA methylation levels in the LPL, ADRB3 and MTHFR genes. A cross-sectional population-based study was conducted with 236 adults (median age 37.5 years) of both sexes from the municipality of João Pessoa, Paraíba, Brazil. The LDL-C concentrations were estimated according to the Friedewald and Martin equations. LPL, ADRB3 and MTHFR gene methylation levels; malondialdehyde levels; total antioxidant capacity; ultra-sensitive C-reactive protein, alpha-1-acid glycoprotein, homocysteine, cobalamin, and folic acid levels; usual dietary intake; and epidemiological variables were also determined. For each unit increase in malondialdehyde concentration there was an increase in the LDL-C concentration from 6.25 to 10.29 mg/dL (p <0.000). Based on the Martin equation (≥70 mg/dL), there was a decrease in the DNA methylation levels in the ADRB3 gene and an increase in the DNA methylation levels in the MTHFR gene (p <0.05). There was a positive relation of homocysteine and cholesterol intake on LDL-C concentrations estimated according to the Friedewald equation and of waist circumference and age based on the two estimates. It is concluded the LDL-C concentrations estimated by the Friedewald and Martin equations were different, and the Friedewald equation values were significantly lower than those obtained by the Martin equation. MDA was the variable that was most positively associated with the estimated LDL-C levels in all multivariate models. Significant relationships were observed based on the two estimates and occurred for most variables. The methylation levels of the ADRB3 and MTHFR genes were different according to the Martin equation at low LDL-C concentrations (70 mg/dL).

Food Intervention with Folate Reduces TNF-α and Interleukin Levels in Overweight and Obese Women with the MTHFR C677T Polymorphism: A Randomized Trial.

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism associated with body fat accumulation could possibly trigger an inflammatory process by elevating homocysteine levels and increasing cytokine production, causing several diseases. This study aimed to evaluate the effects of food intervention, and not folate supplements, on the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) in overweight and obese women with the MTHFR C677T polymorphism. A randomized, double-blind eight-week clinical trial of 48 overweight and obese women was conducted. Participants were randomly assigned into two groups. They received 300 g of vegetables daily for eight weeks containing different doses of folate: 95 µg/day for Group 1 and 191 µg/day for Group 2. MTHFR C677T polymorphism genotyping was assessed by digestion with HinfI enzyme and on 12% polyacrylamide gels. Anthropometric measurements, 24-h dietary recall, and biochemical analysis (blood folic acid, vitamin B12, homocysteine (Hcy), TNF-α, IL-1ß, and IL-6) were determined at the beginning and end of the study. Group 2 had a significant increase in folate intake (p < 0.001) and plasma folic acid (p < 0.05) for individuals with the cytosine-cytosine (CC), cytosine-thymine (CT), and thymine-thymine (TT) genotypes. However, only individuals with the TT genotype presented reduced levels of Hcy, TNF-α, IL-6, and IL-1ß (p < 0.001). Group 1 showed significant differences in folate consumption (p < 0.001) and folic acid levels (p < 0.05) for individuals with the CT and TT genotypes. Food intervention with folate from vegetables increased folic acid levels and reduced interleukins, TNF-α, and Hcy levels, mainly for individuals with the TT genotype.

α-Tocopherol influences glycaemic control and miR-9-3 DNA methylation in overweight and obese women under an energy-restricted diet: a randomized, double-blind, exploratory, controlled clinical trial.

BACKGROUND: Excess weight is a strong risk factor for the development of dysglycaemia. It has been suggested that changes in the metabolism microRNAs, small non-coding RNAs that regulate gene expression, could precede late glycaemic changes. Vitamin E in turn may exert important functions in methylation and gene expression processes. This study aimed to determine the effect of α-tocopherol on glycaemic variables and miR-9-1 and miR-9-3 promoter DNA methylation in overweight women. METHODS: A randomized, double-blind, exploratory, placebo-controlled study was conducted in overweight and obese adult women (n = 44) who ingested synthetic vitamin E (all-rac-α-tocopherol), natural source vitamin E (RRR-rac-α-tocopherol) or placebo capsules and were followed up for a period of 8 weeks. Supplemented groups also received dietary guidance for an energy-restricted diet. An additional group that received no supplementation and did not follow an energy-restricted diet was also followed up. The intervention effect was evaluated by DNA methylation levels (quantitative real-time PCR assay) and anthropometric and biochemical variables (fasting plasma glucose, haemoglobin A1C, insulin, and vitamin E). RESULTS: Increased methylation levels of the miR-9-3 promoter region (P < 0.001) and reduced haemoglobin A1C (P < 0.05) were observed in the natural source vitamin E group after intervention. Increased fasting plasma glucose was observed in the synthetic vitamin E group, despite the significant reduction of anthropometric variables compared to the other groups. CONCLUSIONS: α-Tocopherol from natural sources increased methylation levels of the miR-9-3 promoter region and reduced haemoglobin A1C in overweight women following an energy-restricted diet. These results provide novel information about the influence of vitamin E on DNA methylation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02922491. Registered 4 October, 2016.

Effect of a diet containing folate and hazelnut oil capsule on the methylation level of the ADRB3 gene, lipid profile and oxidative stress in overweight or obese women.

BACKGROUND: Studies of genes that play an important role in the development of obesity are needed, especially studies focusing on genes that regulate food intake and affect nutrient metabolism. For example, the beta-3 adrenergic receptor (ADRB3) responds to noradrenaline and mediates lipolysis in adipocytes. METHODS: This was a controlled intervention study involving 40 overweight and obese adult women in which food intake, anthropometric measurements, biochemical analyses, and methylation levels of the ADRB3 gene were evaluated before and after intervention. The individuals were randomized into four groups: group 1 (G1) received 300 g of vegetables and legumes containing on average 191 µg/day of folate and 1 hazelnut oil capsule; group 2 (G2) received 300 g of vegetables and legumes containing on average 191 µg/day of folate and 1 placebo capsule; group 3 (G3) received 300 g of vegetables and legumes containing on average 90 µg/day of folate and 1 hazelnut oil capsule; and individuals in group 4 (G4) were only followed-up and maintained their regular dietary habits. Statistical analysis was performed using analysis of variance (ANOVA), Student's t test and simple regression, using STATA 13 software. RESULTS: In the total sample, after the intervention, the women classified as overweight and obese did not present weight loss, and there was a reduction in the methylation levels of the ADRB3 gene and malondialdehyde, as well as an increase in high-density lipoprotein cholesterol and total antioxidant capacity. CONCLUSIONS: The beneficial effect of the intake of a hazelnut capsule on the methylation levels of the ADRB3 gene was demonstrated for the first time. TRIAL REGISTRATION: ClinicalTrials.gov, NCT 02846025.

Association between waist-to-height ratio, isolated and combined morbidities and C-reactive protein in the elderly: a clinical-epidemiological study.

The aim of this study was to analyze the association between waist-to-height ratio (WHtR) and C-reactive protein (CRP) in the elderly (considering their most prevalent morbidities and lifestyles), to investigate the relationship between this anthropometric index and the presence of the most prevalent morbidities (isolated or combined), and to identify which morbidities (analyzed individually) would have greater associations with WHtR. This cross-sectional population-based epidemiological study of a stratified sampling comprised 170 elderly individuals between 60 and 90 years of age (both genders). Home visits were used to administer questionnaires and to perform anthropometric measurements and blood collection. The mean patient age was younger than 70 years, with women comprising the majority (69.41%) and with 90% of the patients presenting with inadequate WHtR. Hypertension was the most prevalent morbidity in this cohort (58.52%), and when analyzed in combination, hypertension plus obesity were the most frequently diagnosed morbidities (17.65%). Obesity, which was among the most prevalent comorbidities, was the only comorbidity combined with WHtR (p = 0.0019). Individuals with no morbidities had lower mean WHtR values compared with individuals with at least one morbidity (p = 0.0075). In the multiple linear regression model, it was identified that when individuals had one or more of the most prevalent comorbidities, the mean WHtR increased by 0.0415 (p = 0.0065). A correlation between WHtR and CRP (p = 0.0379) was also verified. Based on the relationships observed between WHtR (isolated or in combination, data unpublished) and CRP among the elderly, WHtR may represent a screening tool because it is a simple and effective anthropometric index.

Methylation profile of the ADRB3 gene and its association with lipid profile and nutritional status in adults

BACKGROUND: Defects in DNA methylation have been shown to be associated with metabolic diseases such as obesity, dyslipidemia, and hypercholesterolemia. To analyze the methylation profile of the ADRB3 gene and correlate it with lipid profile, lipid intake, and oxidative stress based on malondialdehyde (MDA) and total antioxidant capacity (TAC), homocysteine and folic acid levels, nutritional status, lifestyle, and socioeconomic variables in an adult population. A cross-sectional epidemiological study representative of the East and West regions of the municipality of João Pessoa, Paraíba state, Brazil, enrolled 265 adults of both genders. Demographic, lifestyle, and socioeconomic questionnaires and a 24-h recall questionnaire were applied by trained interviewers' home. Nutritional and biochemical evaluation (DNA methylation, lipid profile, MDA, TAC, homocysteine and folic acid levels) was performed. RESULTS: DNA hypermethylation of the ADRB3 gene, analyzed in leukocytes, was present in 50% of subjects and was associated with a higher risk of being overweight (OR 3.28; p = 0.008) or obese (OR 3.06; p = 0.017), a higher waist-hip ratio in males (OR 1.17; p = 0.000), greater intake of trans fats (OR 1.94; p = 0.032), higher LDL (OR 2.64; p = 0.003) and triglycerides (OR 1.81; p = 0.031), and higher folic acid levels (OR 1.85; p = 0.022). CONCLUSIONS: These results suggest that epigenetic changes in the ADRB3 gene locus may explain the development of obesity and non-communicable diseases associated with trans-fat intake, altered lipid profile, and elevated folic acid. Because of its persistence, DNA methylation may have an impact in adults, in association with the development of non-communicable diseases. This study is the first population-based study of the ADRB3 gene, and the data further support evaluation of ADRB3 DNA methylation as an effective biomarker.

Influência dos fatores demográficos, socioeconômicos e de estilo de vida no sobrepeso e obesidade em todas as faixas etárias / Influence of demographic, socioeconomic and lifestyle factors in overweight and obesity in all age groups

Introdução: A prevalência de sobrepeso e obesidade estão relacionadas a idade, sexo, status socioeconômico envolvendo renda e escolaridade, entre outros fatores de risco relacionados à saúde, incluindo tabagismo atual e o sedentarismo. Objetivo: Este trabalho pretende revisar de forma integrada a prevalência de sobrepeso e obesidade em todas as faixas etárias, apresentando evidências atuais sobre o tema e correlacionando com vários fatores que o influenciam. Método: Para a realização desta revisão bibliográfica, foi feita pesquisa em base de dados do PubMed e Medline. Conclusões: Com base nos resultados das pesquisas analisadas, observou-se que a prevalência de sobrepeso é impactante, independentemente da faixa etária e mais prevalente no sexo feminino. Quanto à influência dos fatores demográficos, socioeconômicos e de estilo de vida, não existe consenso, sendo necessárias mais pesquisas buscando diminuir a alta prevalência de sobrepeso, para que essa não se transforme em obesidade.(AU)

Introduction: The prevalence of overweight and obesity are related to age, sex, socioeconomic status, income and education among other risk factors related to health, including current smoking and physical inactivity. Objective: This study aims to review an integrated fashion, the prevalence of overweight and obesity in all age groups, presenting the latest evidence on the subject and correlating with several influencing factors. Methods: For this literature review PubMed and Medline databases were used. Conclusions: Based on the results of the studies analyzed, it was observed that the prevalence of overweight is impressive, regardless of age and more prevalent in females range. As for the influence of demographic, socioeconomic and lifestyle, there is no consensus, and more research is needed to decrease the high prevalence of overweight so this does not become obesity.(AU)

Comparação entre o Conteúdo de Nutrientes nos Rótulos de Alimentos Enriquecidos com Ácido Fólico e Ferro com o Encontrado na Taco e no Software Dietwin / A Comparative Analysis between Nutrient Content Claimed in Folic Acid- And Iron- Enriched Food Labels with that Found in the Brazilian Table of Food Composition and Dietwin Software

Comparar os valores de nutrientes encontrados nosrótulos de alimentos enriquecidos com ácido fólico e ferrocomercializados em João Pessoa com os valores recomendadospela RDC n. 344 da ANVISA de 2002, e com os encontrados naTabela Brasileira de Composição de Alimentos e no softwareDietwin. Material e Métodos: A amostra foi composta pelolevantamento de dados sobre a composição de ácido fólico eferro em 833 alimentos, contendo farinha de milho e farinhade trigo nos dois supermercados que comercializam produtosem nível nacional, localizados no município de João Pessoaonde foram realizas 14 visitas. Todas as análises estatísticasforam realizadas com o auxílio do software Core RDevelopment Team, para verificar as associações, utilizou-seo Teste Qui-quadrado com a concentração dos nutrientes,originados das três fontes de dados. Resultados: Dos 833alimentos analisados, 111(13%) apresentavam valores nosrótulos, 535(64%) tinha a informação de enriquecimento nosingredientes e 187(23%) não apresentavam informação deenriquecimento nos ingredientes. Ao comparar-se os valoresde ácido fólico e ferro, constatou-se que os valores descritosnos rótulos quanto ao ácido fólico eram semelhantes aosvalores encontrados no software Dietwin, e com relação aoferro, os valores encontrados nos rótulos eram superiores aosencontrados no software Dietwin como também em relação aTabela Brasileira de Composição dos Alimentos. Conclusão:No presente estudo observou-se que a fortificação com ácidofólico foi ligeiramente superior ao recomendado com umaumento médio de 10,7%, já a fortificação com ferro supriauma quantidade duas vezes maior, em média, que a obrigatóriaem 26% dos rótulos analisados, com base na legislação vigente...

To compare the nutrient content claimed in folicacid- and iron-enriched food labels commercialized in the cityof João Pessoa, PB, Brazil, with that recommended by theBrazilian Health Surveillance Agency (ANVISA) Decree no.344/2002, and by the Brazilian Table of Food Compositionand Dietwin software. Material and Methods: The sample wascomposed by data about folic acid and iron content in 833food items containing corn and wheat flour. The survey wascompleted after 14 visits in two supermarkets located in JoãoPessoa, which sell national products. All statistical analyseswere performed using the Core R Development Team software.In order to check associations between the nutrient contents inthe three data sources, the Qui-square test was used. Results:Of the 833 items analyzed, 111(13%) presented values in thelabels, 535 (64%) disclosed the information on ingredientenrichment and 187(23%) lacked this sort of information. Wefound that the values described in the labels about folic acidwere similar to those found in Dietwin software, whereas thevalues claimed for iron were greater than the ones found inDietwin software and also in the Brazilian Table of FoodComposition. Conclusion: Folic acid enrichment was slightlyhigher than the recommended with a mean increase of 10.7%,whereas iron enrichment had a two-fold higher amount onaverage than the required one in 26% of the labels analyzedbased on current legislation...