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.

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.

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...