RESUMO
Brain computation performed by billions of nerve cells relies on a sufficient and uninterrupted nutrient and oxygen supply1,2. Astrocytes, the ubiquitous glial neighbours of neurons, govern brain glucose uptake and metabolism3,4, but the exact mechanisms of metabolic coupling between neurons and astrocytes that ensure on-demand support of neuronal energy needs are not fully understood5,6. Here we show, using experimental in vitro and in vivo animal models, that neuronal activity-dependent metabolic activation of astrocytes is mediated by neuromodulator adenosine acting on astrocytic A2B receptors. Stimulation of A2B receptors recruits the canonical cyclic adenosine 3',5'-monophosphate-protein kinase A signalling pathway, leading to rapid activation of astrocyte glucose metabolism and the release of lactate, which supplements the extracellular pool of readily available energy substrates. Experimental mouse models involving conditional deletion of the gene encoding A2B receptors in astrocytes showed that adenosine-mediated metabolic signalling is essential for maintaining synaptic function, especially under conditions of high energy demand or reduced energy supply. Knockdown of A2B receptor expression in astrocytes led to a major reprogramming of brain energy metabolism, prevented synaptic plasticity in the hippocampus, severely impaired recognition memory and disrupted sleep. These data identify the adenosine A2B receptor as an astrocytic sensor of neuronal activity and show that cAMP signalling in astrocytes tunes brain energy metabolism to support its fundamental functions such as sleep and memory.
Assuntos
Adenosina , Astrócitos , Encéfalo , Metabolismo Energético , Neurônios , Transdução de Sinais , Animais , Feminino , Masculino , Camundongos , Ratos , Adenosina/metabolismo , Astrócitos/metabolismo , Encéfalo/metabolismo , Encéfalo/citologia , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Glucose/metabolismo , Hipocampo/metabolismo , Hipocampo/citologia , Ácido Láctico/metabolismo , Camundongos Endogâmicos C57BL , Plasticidade Neuronal , Neurônios/metabolismo , Receptor A2B de Adenosina/deficiência , Receptor A2B de Adenosina/efeitos dos fármacos , Receptor A2B de Adenosina/genética , Receptor A2B de Adenosina/metabolismo , Reconhecimento Psicológico/fisiologia , Sono/genética , Sono/fisiologia , Sinapses/metabolismoRESUMO
BACKGROUND: Recently, we confirmed 24-h urinary sucrose plus fructose (24 uSF) as a predictive biomarker of total sugar intake. However, the collection of 24-h urine samples has limited feasibility in population studies. OBJECTIVE: We investigated the utility of the urinary sucrose plus fructose (uSF) biomarker measured in spot urine as a measure of 24 uSF biomarker and total sugar intake. METHODS: Hundred participants, 18-70 y of age, from the Phoenix Metropolitan Area completed a 15-d feeding study. For 2 of the 8 collected 24-h urine samples, each spot urine sample was collected in a separate container. We considered 4 timed voids of the day [morning (AM) void: first void 08:30-12:30; afternoon (PM) void: first void 12:31-17:30; evening (EVE) void: first void 17:31-12:00; and next-day (ND) void: first void 04:00-12:00]. We investigated the performance of uSF from 1 void, and uSF combined from 2 and 3 voids as a measure of 24 uSF and sugar intake. RESULTS: The biomarker averaged from PM/EVE void strongly correlated with 24 uSF (partial r = 0.75). The 24 uSF predicted from the PM/EVE combination was significantly associated with observed sugar intake and was selected for building the calibrated biomarker equation (marginal R2 = 0.36). Spot urine-based calibrated biomarker, ie, biomarker-estimated sugar intake was moderately correlated with the 15-d mean-observed sugar intake (r = 0.50). CONCLUSIONS: uSF measured from a PM and EVE void may be used to generate biomarker-based sugar intake estimate when collecting 24-h urine samples is not feasible, pending external validation.
Assuntos
Frutose , Sódio , Humanos , Sódio/urina , Coleta de Urina , Carboidratos da Dieta , Biomarcadores/urina , SacaroseRESUMO
Liquid chromatography coupled to mass spectrometry is a key metabolomics/metabonomics technology. Reversed-phase liquid chromatography (RPLC) is very widely used as a separation step, but typically has poor retention of highly polar metabolites. Here, we evaluated the combination of two alternative methods for improving retention of polar metabolites based on 6-aminoquinoloyl-N-hydroxysuccinidimyl carbamate derivatization for amine groups, and ion-pairing chromatography (IPC) using tributylamine as an ion-pairing agent to retain acids. We compared both of these methods to RPLC and also to each other, for targeted analysis using a triple-quadrupole mass spectrometer, applied to a library of ca. 500 polar metabolites. IPC and derivatization were complementary in terms of their coverage: combined, they improved the proportion of metabolites with good retention to 91%, compared to just 39% for RPLC alone. The combined method was assessed by analyzing a set of liver extracts from aged male and female mice that had been treated with the polyphenol compound ampelopsin. Not only were a number of significantly changed metabolites detected, but also it could be shown that there was a clear interaction between ampelopsin treatment and sex, in that the direction of metabolite change was opposite for males and females.
Assuntos
Aminas , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida/métodos , Feminino , Masculino , Metaboloma , Metabolômica/métodos , CamundongosRESUMO
Nitrogen sources are all converted into ammonium/ia as a first step of assimilation. It is reasonable to expect that molecular components involved in the transport of ammonium/ia across biological membranes connect with the regulation of both nitrogen and central metabolism. We applied both genetic (i.e., Δamt mutation) and environmental treatments to a target biological system, the cyanobacterium Anabaena sp PCC 7120. The aim was to both perturb nitrogen metabolism and induce multiple inner nitrogen states, respectively, followed by targeted quantification of key proteins, metabolites and enzyme activities. The absence of AMT transporters triggered a substantial whole-system response, affecting enzyme activities and quantity of proteins and metabolites, spanning nitrogen and carbon metabolisms. Moreover, the Δamt strain displayed a molecular fingerprint indicating nitrogen deficiency even under nitrogen replete conditions. Contrasting with such dynamic adaptations was the striking near-complete lack of an externally measurable altered phenotype. We conclude that this species evolved a highly robust and adaptable molecular network to maintain homeostasis, resulting in substantial internal but minimal external perturbations. This analysis provides evidence for a potential role of AMT transporters in the regulatory/signalling network of nitrogen metabolism and the existence of a novel fourth regulatory mechanism controlling glutamine synthetase activity.
Assuntos
Anabaena/metabolismo , Proteínas de Bactérias/metabolismo , Nitrogênio/metabolismo , Anabaena/genética , Anabaena/crescimento & desenvolvimento , Proteínas de Bactérias/genética , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Deleção de Genes , Mutação , Transdução de SinaisRESUMO
BACKGROUND: Nitrate is converted to nitrite in the human body and subsequently can react with amines and amides in the gastrointestinal tract to form N-nitroso compounds (NOCs), which are known to be carcinogenic in animals. Humans can be exposed to nitrate via consumption of drinking water and diet, especially green leafy vegetables and cured meat. The contribution of nitrate from drinking water in combination with meat intake has not been investigated thoroughly. Therefore, in the present pilot study, we examined the effect of nitrate from drinking water, and its interaction with the consumption of white and processed red meat, on the endogenous formation of NOCs, taking into account the intake of vitamin C, a nitrosation inhibitor. METHODS: Twenty healthy subjects were randomly assigned to two groups consuming either 3.75 g/kg body weight (maximum 300 g per day) processed red meat or unprocessed white meat per day for two weeks. Drinking water nitrate levels were kept low during the first week (< 1.5 mg/L), whereas in week 2, nitrate levels in drinking water were adjusted to the acceptable daily intake level of 3.7 mg/kg bodyweight. At baseline, after 1 and 2 weeks, faeces and 24 h urine samples were collected for analyses of nitrate, apparent total N-nitroso compounds (ATNC), compliance markers, and genotoxic potential in human colonic Caco-2 cells. RESULTS: Urinary nitrate excretion was significantly increased during the high drinking water nitrate period for both meat types. Furthermore, levels of compliance markers for meat intake were significantly increased in urine from subjects consuming processed red meat (i.e. 1-Methylhistidine levels), or unprocessed white meat (i.e. 3-Methylhistidine). ATNC levels significantly increased during the high drinking water nitrate period, which was more pronounced in the processed red meat group. Genotoxicity in Caco-2 cells exposed to faecal water resulted in increased genotoxicity after the interventions, but results were only significant in the low drinking water nitrate period in subjects consuming processed red meat. Furthermore, a positive correlation was found between the ratio of nitrate/vitamin C intake (including drinking water) and the level of ATNC in faecal water of subjects in the processed red meat group, but this was not statistically significant. CONCLUSIONS: Drinking water nitrate significantly contributed to the endogenous formation of NOC, independent of the meat type consumed. This implies that drinking water nitrate levels should be taken into account when evaluating the effect of meat consumption on endogenous formation of NOC. TRIAL REGISTRATION: Dutch Trialregister: 29707 . Registered 19th of October 2018. Retrospectively registered.
Assuntos
Água Potável/química , Carne , Nitratos/análise , Compostos Nitrosos/metabolismo , Adulto , Animais , Galinhas , Feminino , Humanos , Masculino , Carne/classificação , Produtos da Carne , Países Baixos , Músculos Peitorais , Projetos Piloto , Carne de Porco , Distribuição Aleatória , Perus , Adulto JovemRESUMO
The chemical composition of foods is complex, variable, and dependent on many factors. This has a major impact on nutrition research as it foundationally aï¬ects our ability to adequately assess the actual intake of nutrients and other compounds. In spite of this, accurate data on nutrient intake are key for investigating the associations and causal relationships between intake, health, and disease risk at the service of developing evidence-based dietary guidance that enables improvements in population health. Here, we exemplify the importance of this challenge by investigating the impact of food content variability on nutrition research using three bioactives as model: ï¬avan-3-ols, (-)-epicatechin, and nitrate. Our results show that common approaches aimed at addressing the high compositional variability of even the same foods impede the accurate assessment of nutrient intake generally. This suggests that the results of many nutrition studies using food composition data are potentially unreliable and carry greater limitations than commonly appreciated, consequently resulting in dietary recommendations with signiï¬cant limitations and unreliable impact on public health. Thus, current challenges related to nutrient intake assessments need to be addressed and mitigated by the development of improved dietary assessment methods involving the use of nutritional biomarkers.
Studies about the health benefits of foods or nutrients are often inconsistent. One study may find a health benefit of a particular food and may recommend that people increase their consumption of this food to reduce their disease risk. Yet another study may find the opposite. Inconsistent study results fuel confusion and frustration, and reduce trust in research. Limitations in the studies' designs are likely to be blamed for the inconsistent findings. For example, many studies rely on participants to self-report their food intake and on databases of the nutritional content of food. But people may not accurately report their food intake. Foods vary in their nutritional content, even between two items of the same food such as two apples. And how individuals metabolize foods can further affect the nutrients they receive. Nutritional biomarkers are a potential alternative to measuring dietary intake of specific nutrients. Biomarkers are compounds the body produces when it metabolizes a specific nutrient. Measuring biomarkers therefore give scientists a more accurate and unbiased assessment of nutrient intake. Ottaviani et al. conducted a study to test the differences when estimating nutrient intake using nutritional biomarkers compared with more conventional tools. They analyzed data from a nutrition study that involved over 18,000 participants. The experiments used computer modelling to assess study results using self-reported food intake in combination with food composition database information, or measures of three biomarkers estimating the intake of flavan-3-ols, epicatechin, and nitrates. The models showed that self-reported intake and food database information often led to inaccurate results that did not align well with biomarker measurements. Measuring nutritional biomarkers provides a more accurate and unbiased assessment of nutritional intake. Using these measurements instead of traditional methods for measuring nutrient intake may help increase the reliability of nutrition research. Scientists must work to identify and confirm biomarkers of nutrients to facilitate this work. Using these more precise nutrient measurements in studies may result in more consistent results. It may also lead to more trustworthy recommendations for consumers.
Assuntos
Biomarcadores , Autorrelato , Humanos , Catequina/análise , Viés , Ciências da Nutrição , Avaliação Nutricional , Dieta , Análise de AlimentosRESUMO
The underlying mechanisms of plasma metabolite signatures of human aging and age-related diseases are not clear but telomere attrition and dysfunction are central to both. Dyskeratosis congenita (DC) is associated with mutations in the telomerase enzyme complex (TERT, TERC, and DKC1) and progressive telomere attrition. We analyzed the effect of telomere attrition on senescence-associated metabolites in fibroblast-conditioned media and DC patient plasma. Samples were analyzed by gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry. We showed extracellular citrate was repressed by canonical telomerase function in vitro and associated with DC leukocyte telomere attrition in vivo, leading to the hypothesis that altered citrate metabolism detects telomere dysfunction. However, elevated citrate and senescence factors only weakly distinguished DC patients from controls, whereas elevated levels of other tricarboxylic acid cycle (TCA) metabolites, lactate, and especially pyruvate distinguished them with high significance. The DC plasma signature most resembled that of patients with loss of function pyruvate dehydrogenase complex mutations and that of older subjects but significantly not those of type 2 diabetes, lactic acidosis, or elevated mitochondrial reactive oxygen species. Additionally, our data are consistent with further metabolism of citrate and lactate in the liver and kidneys. Citrate uptake in certain organs modulates age-related disease in mice and our data have similarities with age-related disease signatures in humans. Our results have implications for the role of telomere dysfunction in human aging in addition to its early diagnosis and the monitoring of anti-senescence therapeutics, especially those designed to improve telomere function.
Assuntos
Diabetes Mellitus Tipo 2 , Disceratose Congênita , Telomerase , Humanos , Animais , Camundongos , Disceratose Congênita/genética , Disceratose Congênita/metabolismo , Telomerase/genética , Telomerase/metabolismo , Telômero/genética , Telômero/metabolismo , Mutação , Citratos , Lactatos , Proteínas Nucleares/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismoRESUMO
BACKGROUND & AIMS: No effective therapeutic intervention exists for intestinal fibrosis in Crohn's disease [CD]. We characterised fibroblast subtypes, epigenetic and metabolic changes, and signalling pathways in CD fibrosis to inform future therapeutic strategies. METHODS: We undertook immunohistochemistry, metabolic, signalling pathway and Epigenetic [Transposase-Accessible Chromatin using sequencing] analyses associated with collagen production in CCD-18Co intestinal fibroblasts and primary fibroblasts isolated from stricturing [SCD] and non-stricturing [NSCD] CD small intestine. SCD/ NSCD fibroblasts were cultured with TGFß and valproic acid [VPA]. RESULTS: Stricturing CD was characterised by distinct histone deacetylase [HDAC] expression profiles, particularly HDAC1, HDAC2, and HDAC7. As a proxy for HDAC activity, reduced numbers of H3K27ac+ cells were found in SCD compared to NSCD sections. Primary fibroblasts had increased extracellular lactate [increased glycolytic activity] and intracellular hydroxyproline [increased collagen production] in SCD compared to NSCD cultures. The metabolic effect of TGFß-stimulation was reversed by the HDAC inhibitor VPA. SCD fibroblasts appear "metabolically primed" and responded more strongly to both TGFß and VPA. Treatment with VPA revealed TGFß-dependent and independent Collagen-I production in CCD-18Co cells and primary fibroblasts. VPA altered the epigenetic landscape with reduced chromatin accessibility at the COL1A1 and COL1A2 promoters. CONCLUSIONS: Increased HDAC expression profiles, H3K27ac hypoacetylation, a significant glycolytic phenotype, and metabolic priming, characterise SCD-derived as compared to NSCD fibroblasts. Our results reveal a novel epigenetic component to Collagen-I regulation and TGFß-mediated CD fibrosis. HDAC inhibitor therapy may 'reset' the epigenetic changes associated with fibrosis.
RESUMO
BACKGROUND: The serum natural abundance carbon isotope ratio (CIR) was recently identified as a candidate biomarker of animal protein intake in postmenopausal women. Such a biomarker would help clarify the relation between dietary protein source (plant or animal) and chronic disease risk. OBJECTIVES: We aimed to evaluate the performance of the serum CIR as a biomarker of dietary protein source in a controlled feeding study of men and women of diverse age and BMI. METHODS: We conducted a 15-d feeding study of 100 adults (age: 18-70 y, 55% women) in Phoenix, AZ. Participants were provided individualized diets that approximated habitual food intakes. Serum was collected at the end of the feeding period for biomarker measurements. RESULTS: Median [IQR] animal protein intake was 67 g/d [55-88 g/d], which was 64% of total protein. The serum CIR was positively correlated with animal protein and inversely correlated with plant protein intake, leading to a strong correlation (r2 = 0.76) with the dietary animal protein ratio (APR; animal/total protein). Regressing serum CIR on the APR, serum nitrogen isotope ratio (NIR), gender, age, and body weight generated an R2 of 0.78. Following the measurement error model for predictive biomarkers, the resulting regression equation was then inverted to develop a calibrated biomarker equation for APR. Added sugars ratio (added/total sugars intake) and corn intakes also influenced the serum CIR but to a much lesser degree than the APR; variations in these intakes had only small effects on biomarker-estimated APR. CONCLUSIONS: Based on our findings in this US cohort of mixed sex and age, we propose the serum CIR alongside NIR as a predictive dietary biomarker of the APR. We anticipate using this biomarker to generate calibrated estimates based on self-reported intake and ultimately to obtain more precise disease risk estimates according to dietary protein source.
Assuntos
Dieta , Proteínas Animais da Dieta , Animais , Biomarcadores , Isótopos de Carbono , Feminino , Humanos , Masculino , Isótopos de NitrogênioRESUMO
Previous studies suggest that amino acid carbon stable isotope ratios (CIRAAs) may serve as biomarkers of added sugar (AS) intake, but this has not been tested in a demographically diverse population. We conducted a 15-day feeding study of U.S. adults, recruited across sex, age, and BMI groups. Participants consumed personalized diets that resembled habitual intake, assessed using two consecutive 7-day food records. We measured serum (n = 99) CIRAAs collected at the end of the feeding period and determined correlations with diet. We used forward selection to model AS intake using participant characteristics and 15 CIRAAs. This model was internally validated using bootstrap optimism correction. Median (25th, 75th percentile) AS intake was 65.2 g/day (44.7, 81.4) and 9.5% (7.2%, 12.4%) of energy. The CIR of alanine had the highest, although modest, correlation with AS intake (r = 0.32, p = 0.001). Serum CIRAAs were more highly correlated with animal food intakes, especially the ratio of animal to total protein. The AS model included sex, body weight and 6 CIRAAs. This model had modest explanatory power (multiple R2 = 0.38), and the optimism-corrected R2 was lower (R2 = 0.15). Further investigations in populations with wider ranges of AS intake are warranted.
Assuntos
Aminoácidos , Dieta , Animais , Humanos , Isótopos de Carbono , Biomarcadores , Alanina , Açúcares , Comportamento Alimentar , Ingestão de EnergiaRESUMO
BACKGROUND: Twenty-four-hour urinary sucrose and fructose (24uSF) has been studied as a biomarker of total sugars intake in two feeding studies conducted in the United Kingdom (UK) and Arizona (AZ). We compare the biomarker performance in these populations, testing whether it meets the criteria for a predictive biomarker. METHODS: The UK and AZ feeding studies included 13 and 98 participants, respectively, aged 18 to 70 years, consuming their usual diet under controlled conditions. Linear mixed models relating 24uSF to total sugars and personal characteristics were developed in each study and compared. The AZ calibrated biomarker equation was applied to generate biomarker-estimated total sugars intake in UK participants. Stability of the model across AZ study subpopulations was also examined. RESULTS: Model coefficients were similar between the two studies [e.g., log(total sugars): UK 0.99, AZ 1.03, P = 0.67], as was the ratio of calibrated biomarker person-specific bias to between-person variance (UK 0.32, AZ 0.25, P = 0.68). The AZ equation estimated UK log(total sugar intakes) with mean squared prediction error of 0.27, similar to the AZ study estimate (0.28). Within the AZ study, the regression coefficients of log(total sugars) were similar across age, gender, and body mass index subpopulations. CONCLUSIONS: Similar model coefficients in the two studies and good prediction of UK sugar intakes by the AZ equation suggest that 24uSF meets the criteria for a predictive biomarker. Testing the biomarker performance in other populations is advisable. IMPACT: Applications of the 24uSF biomarker will enable improved assessment of the role of sugars intake in risk of chronic disease, including cancer. See related commentary by Prentice, p. 1151.
Assuntos
Frutose , Sacarose , Biomarcadores , Índice de Massa Corporal , Humanos , Reino UnidoRESUMO
BACKGROUND: Developing approaches for the objective assessment of sugars intake in population research is crucial for generating reliable disease risk estimates, and evidence-based dietary guidelines. Twenty-four-hour urinary sucrose and fructose (24uSF) was developed as a predictive biomarker of total sugars intake based on 3 UK feeding studies, yet its performance as a biomarker of total sugars among US participants is unknown. OBJECTIVES: To investigate the performance of 24uSF as a biomarker of sugars intake among US participants, and to characterize its use. METHODS: Ninety-eight participants, aged 18-70 y, consumed their usual diet under controlled conditions of a feeding study for 15 d, and collected 8 nonconsecutive 24-h urines measured for sucrose and fructose. RESULTS: A linear mixed model regressing log 24uSF biomarker on log total sugars intake along with other covariates explained 56% of the biomarker variance. Total sugars intake was the strongest predictor in the model (Marginal R2 = 0.52; P <0.0001), followed by sex (P = 0.0002) and log age (P = 0.002). The equation was then inverted to solve for total sugars intake, thus generating a calibrated biomarker equation. Calibration of the biomarker produced mean biomarker-based log total sugars of 4.79 (SD = 0.59), which was similar to the observed log 15-d mean total sugars intake of 4.69 (0.35). The correlation between calibrated biomarker and usual total sugars intake was 0.59 for the calibrated biomarker based on a single biomarker measurement, and 0.76 based on 4 biomarker repeats spaced far apart. CONCLUSIONS: In this controlled feeding study, total sugars intake was the main determinant of 24uSF confirming its utility as a biomarker of total sugars in this population. Next steps will include validation of stability assumptions of the biomarker calibration equation proposed here, which will allow its use as an instrument for dietary validation and measurement error correction in diet-disease association studies.
Assuntos
Carboidratos da Dieta/urina , Frutose/urina , Sacarose/urina , Adolescente , Adulto , Idoso , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Estados Unidos , Adulto JovemRESUMO
SCOPE: It has been proposed that endogenously form N-nitroso compounds (NOCs) are partly responsible for the link between red meat consumption and colorectal cancer (CRC) risk. As nitrite has been indicated as critical factor in the formation of NOCs, the impact of replacing the additive sodium nitrite (E250) by botanical extracts in the PHYTOME project is evaluated. METHOD AND RESULTS: A human dietary intervention study is conducted in which healthy subjects consume 300 g of meat for 2 weeks, in subsequent order: conventional processed red meat, white meat, and processed red meat with standard or reduced levels of nitrite and added phytochemicals. Consumption of red meat products enriched with phytochemicals leads to a significant reduction in the faecal excretion of NOCs, as compared to traditionally processed red meat products. Gene expression changes identify cell proliferation as main affects molecular mechanism. High nitrate levels in drinking water in combination with processed red meat intake further stimulates NOC formation, an effect that could be mitigated by replacement of E250 by natural plant extracts. CONCLUSION: These findings suggest that addition of natural extracts to conventionally processed red meat products may help to reduce CRC risk, which is mechanistically support by gene expression analyses.
Assuntos
Neoplasias Colorretais/prevenção & controle , Produtos da Carne , Nitritos/efeitos adversos , Compostos Nitrosos/metabolismo , Compostos Fitoquímicos/administração & dosagem , Extratos Vegetais/administração & dosagem , Carne Vermelha , Adulto , Células CACO-2 , Feminino , Humanos , Masculino , Produtos da Carne/análise , Compostos Nitrosos/efeitos adversos , Carne Vermelha/análise , Adulto JovemRESUMO
Obesity is an important modifiable risk factor for chronic diseases. While there is increasing focus on the role of dietary sugars, there remains a paucity of data establishing the association between sugar intake and obesity in the general public. The objective of this study was to investigate associations of estimated sugar intake with odds for obesity in a representative sample of English adults. We used data from 434 participants of the 2005 Health Survey of England. Biomarkers for total sugar intake were measured in 24 h urine samples and used to estimate intake. Linear and logistic regression analyses were used to investigate associations between biomarker-based estimated intake and measures of obesity (body mass intake (BMI), waist circumference and waist-to-hip ratio) and obesity risk, respectively. Estimated sugar intake was significantly associated with BMI, waist circumference and waist-to-hip ratio; these associations remained significant after adjustment for estimated protein intake as a marker of non-sugar energy intake. Estimated sugar intake was also associated with increased odds for obesity based on BMI (OR 1.02; 95%CI 1.00-1.04 per 10g), waist-circumference (1.03; 1.01-1.05) and waist-to-hip ratio (1.04; 1.02-1.06); all OR estimates remained significant after adjusting for estimated protein intake. Our results strongly support positive associations between total sugar intake, measures of obesity and likelihood of being obese. It is the first time that such an association has been shown in a nationally-representative sample of the general population using a validated biomarker. This biomarker could be used to monitor the efficacy of public health interventions to reduce sugar intake.
Assuntos
Sacarose Alimentar/urina , Obesidade/diagnóstico , Adulto , Biomarcadores/urina , Índice de Massa Corporal , Estudos Transversais , Ingestão de Energia , Inglaterra , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/urina , Fatores de Risco , Circunferência da Cintura/fisiologia , Relação Cintura-QuadrilRESUMO
BACKGROUND: The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic nitrate content. OBJECTIVE: We sought to examine the effects of a 6-wk once-daily intake of dietary nitrate (nitrate-rich beetroot juice) compared with placebo intake (nitrate-depleted beetroot juice) on vascular and platelet function in untreated hypercholesterolemics. DESIGN: A total of 69 subjects were recruited in this randomized, double-blind, placebo-controlled parallel study. The primary endpoint was the change in vascular function determined with the use of ultrasound flow-mediated dilatation (FMD). RESULTS: Baseline characteristics were similar between the groups, with primary outcome data available for 67 patients. Dietary nitrate resulted in an absolute increase in the FMD response of 1.1% (an â¼24% improvement from baseline) with a worsening of 0.3% in the placebo group (P < 0.001). A small improvement in the aortic pulse wave velocity (i.e., a decrease of 0.22 m/s; 95% CI: -0.4, -0.3 m/s) was evident in the nitrate group, showing a trend (P = 0.06) to improvement in comparison with the placebo group. Dietary nitrate also caused a small but significant reduction (7.6%) in platelet-monocyte aggregates compared with an increase of 10.1% in the placebo group (P = 0.004), with statistically significant reductions in stimulated (ex vivo) P-selectin expression compared with the placebo group (P < 0.05) but no significant changes in unstimulated expression. No adverse effects of dietary nitrate were detected. The composition of the salivary microbiome was altered after the nitrate treatment but not after the placebo treatment (P < 0.01). The proportions of 78 bacterial taxa were different after the nitrate treatment; of those taxa present, 2 taxa were responsible for >1% of this change, with the proportions of Rothia mucilaginosa trending to increase and Neisseria flavescens (P < 0.01) increased after nitrate treatment relative to after placebo treatment. CONCLUSIONS: Sustained dietary nitrate ingestion improves vascular function in hypercholesterolemic patients. These changes are associated with alterations in the oral microbiome and, in particular, nitrate-reducing genera. Our findings provide additional support for the assessment of the potential of dietary nitrate as a preventative strategy against atherogenesis in larger cohorts. This trial was registered at clinicaltrials.gov as NCT01493752.
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Beta vulgaris/química , Dieta , Hipercolesterolemia , Nitratos/farmacologia , Vasodilatação/efeitos dos fármacos , Verduras/química , Adulto , Aterosclerose/sangue , Aterosclerose/prevenção & controle , Bactérias/metabolismo , Plaquetas/metabolismo , Método Duplo-Cego , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Mucosa Bucal/microbiologia , Nitratos/uso terapêutico , Nitritos/metabolismo , Selectina-P/sangue , Saliva/microbiologiaRESUMO
Mineral, spring and tap water samples of different geographical origins (7 classes) were distinguished by various methods, such as sensory evaluation, electronic tongue measurement, inductively coupled plasma atomic emission spectroscopy and ion chromatography. Samples from the same geographical origin were correctly classified by chemical analysis and electronic tongue (100%), but it was found that only 80% classification rate can be achieved by sensory evaluation. Different water brands (different brand names) from the same geographical origin did not show definite differences, as expected. Forward stepwise algorithm selected three chemical parameters namely, chloride (Cl(-)), sulphate (SO(4)(2-)) and magnesium (Mg) content and two electronic tongue sensor signals (ZZ and HA) to discriminate according to the geographical origins.
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Técnicas Eletroquímicas/métodos , Águas Minerais/análise , Paladar , Técnicas Eletroquímicas/instrumentação , Feminino , Humanos , MasculinoRESUMO
The paper describes the application of SOMs (Self-Organizing Maps) and SVR (Support Vector Regression) to pattern recognition in GC-MS (gas chromatography-mass spectrometry). The data are applied to two groups of apples, one which is a control and one which has been inoculated with Penicillium expansum and which becomes spoiled over the 10-day period of the experiment. GC-MS of SPME (solid phase microextraction) samples of volatiles from these apples were recorded, on replicate samples, over time, to give 58 samples used for pattern recognition and a peak table obtained. A new approach for finding the optimum SVR parameters called differential evolution is described. SOMs are presented in the form of two-dimensional maps. This paper shows the potential of using machine learning methods for pattern recognition in analytical chemistry, particularly as applied to food chemistry and biology where trends are likely to be non-linear.