RESUMEN
INTRODUCTION: Women and infants are among the most vulnerable groups for micronutrient deficiencies. Pregnancy micronutrient status can affect birth outcomes and subsequent infants' growth. METHODS: We determined the relationship between maternal iron and vitamin A status at delivery using several biomarkers (ferritin, soluble transferrin receptor [sTFR], body iron stores [BIS], hemoglobin and retinol binding protein [RBP]) and birth outcomes (body weight, Z-scores, head circumference, small-for-gestational-age and preterm birth) in rural Uganda. We investigated women who had serum results at the point of delivery and paired them to their infants at birth (n = 1244). We employed multivariable linear and logistic regression, adjusting for clustering at the subcounty level to determine the relationship between maternal micronutrients and birth outcomes. RESULTS: After adjusting for relevant factors, we found that maternal iron status (ferritin and BIS) and anemia (hemoglobin) were not significantly associated with the assessed birth outcomes. However, there was a significant association between serum sTFR and preterm births (AOR: 0.67; 95% CI 0.48-0.94). For Vitamin A, we observed a significant positive association between RBP and length-for-age (LAZ) at birth (ß = 0.12, p < 0.030). DISCUSSION: These findings indicate that the relationship between maternal iron status and birth outcomes needs to be further investigated, because depending on the biomarker used the associations were either in favor of an adverse birth outcome or not significant. Additionally, they confirm that higher maternal RBP levels could be beneficial for birth outcomes. CLINICALTRIALS: gov as NCT04233944.
Asunto(s)
Nacimiento Prematuro , Vitamina A , Biomarcadores , Cohorte de Nacimiento , Estudios de Cohortes , Femenino , Ferritinas , Hemoglobinas/análisis , Humanos , Lactante , Recién Nacido , Hierro , Micronutrientes , Embarazo , Mujeres Embarazadas , Nacimiento Prematuro/inducido químicamente , Nacimiento Prematuro/epidemiología , Receptores de Transferrina , Uganda/epidemiología , Vitamina A/metabolismoRESUMEN
In rural Bangladesh, intake of nutrient-rich foods, such as animal source foods (ASFs), is generally suboptimal. Diets low in nutrients and lacking in diversity put women of reproductive age (WRA) at risk of malnutrition as well as adverse birth outcomes. The objective of this study was to assess the relationship between maternal dietary diversity, consumption of specific food groups and markers of nutritional status, including underweight [body mass index (BMI) < 18.5 kg/m2 ], overweight (BMI ≥ 23 kg/m2 ) and anaemia (haemoglobin < 120 g/dl) among WRA in Bangladesh. This analysis used data from the third round of a longitudinal observational study, collected from February through May of 2017. Dietary data were collected with a questionnaire, and Women's Dietary Diversity Score (WDDS) was calculated. Associations between WDDS, food group consumption and markers of nutritional status were assessed with separate adjusted logistic regression models. Among WRA, the prevalence of underweight, overweight and anaemia was 13.38%, 40.94% and 39.99%, respectively. Women who consumed dark green leafy vegetables (DGLV) or eggs were less likely to be anaemic or underweight, respectively, and women who consumed ASFs, particularly fish, were less likely to be underweight compared with women who did not consume these foods. WDDS did not show any consistent relationship with WRA outcomes. Interventions that focus on promoting optimal nutritional status among WRA in Bangladesh should emphasise increasing consumption of specific nutrient-rich foods, including ASFs, DGLV and eggs, rather than solely focusing on improving diet diversity in general.
Asunto(s)
Estado Nutricional , Población Rural , Animales , Bangladesh/epidemiología , Dieta , Femenino , Humanos , VerdurasRESUMEN
Childhood stunting remains a public health burden worldwide. Although many studies have examined early life and in-utero risk factors; most have been observational and have used analytic techniques that make inferences limited to population means, thereby obscuring important within-group variations. This study addressed that important gap. Using data from a birth cohort of Ugandan infants (n = 4528), we applied group-based trajectory modelling to assess diverse patterns of growth among children from birth to 1-year old. A multinomial regression model was conducted to understand the relationship between risk factors and observed patterns across groups. We found that the onset of stunting occurred before birth and followed four distinct growth patterns: chronically stunted (Group 1), recovery (Group 2), borderline stunted (Group 3) and normal (Group 4). The average length-for-age z-score (LAZ) at birth was -2.6, -3.9, -0.6 and 0.5 for Groups 1-4, respectively. Although both Groups 1 and 2 were stunted at birth, stunting persisted in Group 1 while children in Group 2 recovered by the fourth month. Group 3 exhibited mild stunting while Group 4 was normal. Wasting and underweight were observed in all groups, with the highest prevalence of underweight in Group 1. Wasting gradually increased among children born already stunted (Groups 1 and 2). This showed the importance of distinguishing children by their growth patterns rather than aggregating them and only comparing population averages against global growth standards. The design of nutrition interventions should consider the differential factors and potential for growth gains relative to different risks within each group.
Asunto(s)
Trastornos del Crecimiento , Delgadez , Niño , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/etiología , Humanos , Lactante , Recién Nacido , Prevalencia , Factores de Riesgo , Delgadez/epidemiología , Uganda/epidemiologíaRESUMEN
BACKGROUND: The public health burden of undernutrition remains heavy and widespread, especially in low-income countries like Nepal. While predictors of undernutrition are well documented, few studies have examined the effects of political will and quality of policy or program implementation on child growth. METHODS: Data were collected from two nationwide studies in Nepal to determine the relationship between a metric of nutrition 'governance' (the Nutrition Governance Index), derived from interviews with 520 government and non-government officials responsible for policy implementation and anthropometry measured for 6815 children in 5556 households. We employed Generalized Estimating Equation (GEE) and multilevel regression models. RESULTS: A higher NGI (more effective nutrition governance) is positively associated with height-for-age as well as weight-for-height in children over 2 years of age compared to younger children (HAZ; ß = 0.02, p < 0.004, WHZ; ß = 0.01, p < 0.37). Results from the hierarchical model show that a one-point increase in the NGI is significantly associated with a 12% increase in HAZ and a 4% increase in WHZ in older children (> 24 months old). Mothers' education, child's age, BMI and no fever in the past 30 days were also protective of stunting and wasting. Seven percent and 17% of the overall variance in HAZ and WHZ, respectively, are accounted for by variations across the 21 district locations in which sampled households were located. Mean HAZ differs considerably across districts (intercept = 0.116, p < 0.001). CONCLUSIONS: These results highlight the importance of effective management of policy-based programming and resource use to bring about nutrition gains on the ground. The NGI explained a non-negligible amount of variation in HAZ and WHZ, which underscores the fundamental role that good governance plays in promoting child nutrition and growth, and the value of seeking to measure it to assist governments in moving policies from paper to practice.
Asunto(s)
Desnutrición , Estado Nutricional , Niño , Preescolar , Composición Familiar , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/etiología , Trastornos del Crecimiento/prevención & control , Humanos , Lactante , Nepal/epidemiologíaRESUMEN
BACKGROUND: Environmental enteric dysfunction (EED), characterized by altered intestinal permeability/inflammation, microbial translocation, and systemic inflammation (SI), may be a significant contributor to micronutrient deficiencies and poor growth in infants from low-resource settings. OBJECTIVE: We examined associations among EED, SI, growth, and iron status at 6 mo of age. METHODS: We performed a cross-sectional analysis of 6-mo-old infants (n = 548) enrolled in a Ugandan birth-cohort study (NCT04233944). EED was assessed via serum concentrations of anti-flagellin and anti- LPS immunoglobulins (Igs); SI was assessed via serum concentrations of É1-acid glycoprotein (AGP) and C-reactive protein (CRP); iron status was assessed via serum concentrations of hemoglobin (Hb), soluble transferrin receptor (sTfR), and ferritin. Associations were assessed using adjusted linear regression analysis. RESULTS: At 6 mo, â¼35% of infants were stunted [length-for-age z score (LAZ) < -2] and â¼53% were anemic [hemoglobin (Hb) <11.0 g/dL]. Nearly half (â¼46%) had elevated AGP (>1 g/L) and â¼30% had elevated CRP (>5 mg/L). EED and SI biomarkers were significantly correlated (r = 0.142-0.193, P < 0.001 for all). In adjusted linear regression models, which included adjustments for SI, higher anti-flagellin IgA, anti-LPS IgA, and anti-LPS IgG concentrations were each significantly associated with lower LAZ [ß (95% CI): -0.21 (-0.41, 0.00), -0.23 (-0.44, -0.03), and -0.33 (-0.58, -0.09)]. Furthermore, higher anti-flagellin IgA, anti-flagellin IgG, and anti-LPS IgA concentrations were significantly associated with lower Hb [ß (95% CI): -0.24 (-0.45, -0.02), -0.58 (-1.13, 0.00), and -0.26 (-0.51, 0.00)] and higher anti-flagellin IgG and anti-LPS IgG concentrations were significantly associated with higher sTfR [ß (95% CI): 2.31 (0.34, 4.28) and 3.13 (0.75, 5.51)]. CONCLUSIONS: EED is associated with both low LAZ and iron status in 6-mo-old infants. Further research on the mechanisms by which EED affects growth and micronutrient status is warranted.
Asunto(s)
Anemia Ferropénica/epidemiología , Anemia Ferropénica/etiología , Desarrollo Infantil , Enfermedades Intestinales/microbiología , Enfermedades Intestinales/patología , Población Rural , Adulto , Estudios de Cohortes , Femenino , Microbioma Gastrointestinal , Humanos , Lactante , Inflamación , Enfermedades Intestinales/epidemiología , Masculino , Uganda/epidemiología , Adulto JovenRESUMEN
BACKGROUND: ß-Cryptoxanthin (BCX), a provitamin A carotenoid shown to protect against nonalcoholic fatty liver disease (NAFLD), can be cleaved by ß-carotene-15,15'-oxygenase (BCO1) to generate vitamin A, and by ß-carotene-9',10'-oxygenase (BCO2) to produce bioactive apo-carotenoids. BCO1/BCO2 polymorphisms have been associated with variations in plasma carotenoid amounts in both humans and animals. OBJECTIVES: We investigated whether BCX feeding inhibits high refined-carbohydrate diet (HRCD)-induced NAFLD, dependent or independent of BCO1/BCO2. METHODS: Six-week-old male wild-type (WT) and BCO1-/-/BCO2-/- double knockout (DKO) mice were randomly fed HRCD (66.5% of energy from carbohydrate) with or without BCX (10 mg/kg diet) for 24 wk. Pathological and biochemical variables were analyzed in the liver and mesenteric adipose tissues (MATs). Data were analyzed by 2-factor ANOVA. RESULTS: Compared to their respective HRCD controls, BCX reduced hepatic steatosis severity by 33â43% and hepatic total cholesterol by 43â70% in both WT and DKO mice (P < 0.01). Hepatic concentrations of BCX, but not retinol and retinyl palmitate, were 33-fold higher in DKO mice than in WT mice (P < 0.001). BCX feeding increased the hepatic fatty acid oxidation protein peroxisome proliferator-activated receptor-α, and the cholesterol efflux gene ATP-binding cassette transporter5, and suppressed the lipogenesis gene acetyl-CoA carboxylase 1 (Acc1) in the MAT of WT mice but not DKO mice (P < 0.05). BCX feeding decreased the hepatic lipogenesis proteins ACC and stearoyl-CoA desaturase-1 (3-fold and 5-fold) and the cholesterol synthesis genes 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase and HMG-CoA synthase 1 (2.7-fold and 1.8-fold) and increased the cholesterol catabolism gene cholesterol 7α-hydroxylase (1.9-fold) in the DKO but not WT mice (P < 0.05). BCX feeding increased hepatic protein sirtuin1 (2.5-fold) and AMP-activated protein kinase (9-fold) and decreased hepatic farnesoid X receptor protein (80%) and the inflammatory cytokine gene Il6 (6-fold) in the MAT of DKO mice but not WT mice (P < 0.05). CONCLUSION: BCX feeding mitigates HRCD-induced NAFLD in both WT and DKO mice through different mechanisms in the liver-MAT axis, depending on the presence or absence of BCO1/BCO2.
Asunto(s)
beta-Criptoxantina/administración & dosificación , Carbohidratos de la Dieta/efectos adversos , Dioxigenasas/fisiología , Enfermedad del Hígado Graso no Alcohólico/prevención & control , beta-Caroteno 15,15'-Monooxigenasa/fisiología , Adenilato Quinasa/fisiología , Tejido Adiposo/metabolismo , Animales , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Sirtuina 1/fisiologíaRESUMEN
Aflatoxins are toxic metabolites of Aspergillus moulds and are widespread in the food supply, particularly in low- and middle-income countries. Both in utero and infant exposure to aflatoxin B1 (AFB1 ) have been linked to poor child growth and development. The objective of this prospective cohort study was to investigate the association between maternal aflatoxin exposure during pregnancy and adverse birth outcomes, primarily lower birth weight, in a sample of 220 mother-infant pairs in Mukono district, Uganda. Maternal aflatoxin exposure was assessed by measuring the serum concentration of AFB1 -lysine (AFB-Lys) adduct at 17.8 ± 3.5 (mean ± SD)-week gestation using high-performance liquid chromatography. Anthropometry and birth outcome characteristics were obtained within 48 hr of delivery. Associations between maternal aflatoxin exposure and birth outcomes were assessed using multivariable linear regression models adjusted for confounding factors. Median maternal AFB-Lys level was 5.83 pg/mg albumin (range: 0.71-95.60 pg/mg albumin, interquartile range: 3.53-9.62 pg/mg albumin). In adjusted linear regression models, elevations in maternal AFB-Lys levels were significantly associated with lower weight (adj-ß: 0.07; 95% CI: -0.13, -0.003; p = 0.040), lower weight-for-age z-score (adj-ß: -0.16; 95% CI: -0.30, -0.01; p = 0.037), smaller head circumference (adj-ß: -0.26; 95% CI: -0.49, -0.02; p = 0.035), and lower head circumference-for-age z-score (adj-ß: -0.23; 95% CI: -0.43, -0.03; p = 0.023) in infants at birth. Overall, our data suggest an association between maternal aflatoxin exposure during pregnancy and adverse birth outcomes, particularly lower birth weight and smaller head circumference, but further research is warranted.
Asunto(s)
Aflatoxinas/efectos adversos , Contaminación de Alimentos/estadística & datos numéricos , Recién Nacido de Bajo Peso , Exposición Materna/efectos adversos , Complicaciones del Embarazo/epidemiología , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , Exposición Materna/estadística & datos numéricos , Embarazo , Estudios Prospectivos , Uganda/epidemiología , Adulto JovenRESUMEN
Sirtuin 1 (SIRT1) has been reported to protect against nonalcoholic fatty liver disease (NAFLD) development. The mechanism of how SIRT1 deacetylase activity affects NAFLD has not been well investigated. The current investigation addressed the causal effect of systemic SIRT1 activity on NAFLD development and the underlying mechanism involved in both liver and mesenteric adipose tissue (MAT). Both SIRT1 homozygous mice ablated the catalytic activity (sirt1Y/Y) and their corresponding wild type littermates (WT) were fed a high fat diet (HFD, 60% calories from fat) for 34weeks. Sirt1Y/Y mice showed significantly higher level of hepatic triglyceride which was accompanied with higher levels of SREBP-1 and SCD1and decreased phosphorylation of LKB1 and AMPK in the liver. Compared with WT mice, mRNA expression of lipogenic genes (lxrα, srebp-1c, scd1 and fas) in the MAT increased significantly in sirt1Y/Y mice. Fatty acid oxidation biomarkers (acox1, acox3, cpt, ucp1, sirt3) in both liver and MAT were comparable between groups. Interestingly, we observed that in sirt1Y/Y mice, the mRNA level of hormone sensitive lipase (hsl), adipose triglyceride lipase (atgl) and perilipin-2 (plin-2), all involved in lipolysis, significantly increased in MAT, but not in epididymal adipose tissue. These changes positively correlated with circulating free fatty acid (FFA) concentrations and higher hepatic mRNA expression of cd36 for FFA uptake. The present study has provided novel evidence to suggest that under HFD-induced metabolic surplus, the lack of SIRT1 catalytic activity promotes release of FFA from MAT and escalate NAFLD by interfering with lipid homeostasis in both liver and MAT.
Asunto(s)
Tejido Adiposo/metabolismo , Ácidos Grasos/metabolismo , Hígado/metabolismo , Mesenterio/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Sirtuina 1/metabolismo , Tejido Adiposo/patología , Animales , Regulación de la Expresión Génica , Lipogénesis , Hígado/patología , Mesenterio/patología , Ratones , Ratones Mutantes , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/patología , Sirtuina 1/genéticaRESUMEN
PURPOSE: Global DNA hydroxymethylation is markedly decreased in human cancers, including hepatocellular carcinoma, which is associated with chronic alcohol consumption and aging. Because gene-specific changes in hydroxymethylcytosine may affect gene transcription, giving rise to a carcinogenic environment, we determined genome-wide site-specific changes in hepatic hydroxymethylcytosine that are associated with chronic alcohol consumption and aging. METHODS: Young (4 months) and old (18 months) male C57Bl/6 mice were fed either an ethanol-containing Lieber-DeCarli liquid diet or an isocaloric control diet for 5 weeks. Genomic and gene-specific hydroxymethylcytosine patterns were determined through hydroxymethyl DNA immunoprecipitation array in hepatic DNA. RESULTS: Hydroxymethylcytosine patterns were more perturbed by alcohol consumption in young mice than in old mice (431 differentially hydroxymethylated regions, DhMRs, in young vs 189 DhMRs in old). A CpG island ~2.5 kb upstream of the glucocorticoid receptor gene, Nr3c1, had increased hydroxymethylation as well as increased mRNA expression (p = 0.015) in young mice fed alcohol relative to the control group. Aging alone also altered hydroxymethylcytosine patterns, with 331 DhMRs, but alcohol attenuated this effect. Aging was associated with a decrease in hydroxymethylcytosine ~1 kb upstream of the leptin receptor gene, Lepr, and decreased transcription of this gene (p = 0.029). Nr3c1 and Lepr are both involved in hepatic lipid homeostasis and hepatosteatosis, which may create a carcinogenic environment. CONCLUSIONS: These results suggest that the location of hydroxymethylcytosine in the genome is site specific and not random, and that changes in hydroxymethylation may play a role in the liver's response to aging and alcohol.
Asunto(s)
Envejecimiento/metabolismo , Consumo de Bebidas Alcohólicas/metabolismo , Metilación de ADN , Hígado/metabolismo , Alcoholismo/metabolismo , Animales , Citosina/análisis , Citosina/química , Citosina/metabolismo , ADN/química , ADN/metabolismo , Metilación de ADN/genética , Hígado Graso/genética , Redes Reguladoras de Genes , Homeostasis/genética , Hidroxilación/genética , Metabolismo de los Lípidos/genética , Hígado/química , Masculino , Ratones , Ratones Endogámicos C57BL , Receptores de Leptina/genéticaRESUMEN
BACKGROUND: Vitamin D homeostasis may play a critical role in glucose metabolism. Little is known on vitamin D deficiency and its association with diabetes in countries of the Arabia Gulf where the population is experiencing a rapid increase in the incidence of diabetes. METHODS: In a cross-sectional study of 960 adults enrolled in the first National Nutrition Survey of the State of Kuwait (NNSSK), we examined vitamin D status in association with the prevalence of diabetes and prediabetes. Vitamin D status was measured by serum levels of 25-hydroxyvitami D (25(OH)D). Prevalences of diabetes and prediabetes were determined based on fasting glucose and HbA1C levels. RESULTS: The median level of serum 25(OH)D in Kuwaiti adults was 13.8 ng/ml. Approximately 56 % of the Kuwaiti adults had vitamin D inadequacy (25(OH)D = 12-19.9 ng/ml), and 27 % had vitamin D deficiency (25(OH)D < 12 ng/ml). The prevalences of prediabetes and diabetes were 40 and 27 %, respectively. Vitamin D inadequacy (OR = 1.7, 95 % CI: 1.0-2.9) and deficiency (OR =2.0, 95 % CI: 1.1-3.3) was each associated with about two-fold increased odds of prediabetes compared to sufficient vitamin D status (25(OH)D ≥ 20 ng/ml). Vitamin D inadequacy (OR =2.1, 95 % CI: 1.2-3.7) and deficiency (OR =2.0, 95 % CI: 1.1-3.9) were also associated with two-fold increased odds of diabetes. CONCLUSIONS: Data from Kuwaiti's first nutrition nutritional survey suggests a very high prevalence of vitamin D deficiency in Kuwaiti adults. Associations of low vitamin D status and high prevalence of diabetes point to the need of continuous monitoring of vitamin D status and further evaluating potential health consequences in this high-risk population.
Asunto(s)
Estado Prediabético/epidemiología , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/epidemiología , Vitamina D/análogos & derivados , Adulto , Anciano , Comorbilidad , Estudios Transversales , Femenino , Humanos , Kuwait/epidemiología , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Estado Nutricional , Estado Prediabético/diagnóstico , Prevalencia , Factores de Riesgo , Vitamina D/sangre , Adulto JovenRESUMEN
Chronic and excessive alcohol consumption leads to the development of alcoholic liver disease (ALD) and greatly increases the risk of liver cancer. Induction of the cytochrome p450 2E1 (CYP2E1) enzyme by chronic and excessive alcohol intake is known to play a role in the pathogenesis of ALD. High intake of tomatoes, rich in the carotenoid lycopene, is associated with a decreased risk of chronic disease. We investigated the effects of whole tomato (tomato powder, TP), partial tomato (tomato extract, TE), and purified lycopene (LYC) against ALD development in rats. Of the three supplements, only TP reduced the severity of alcohol-induced steatosis, hepatic inflammatory foci, and CYP2E1 protein levels. TE had no effect on these outcomes and LYC greatly increased inflammatory foci in alcohol-fed rats. To further support the protective effect of TP against ALD, TP was supplemented in a carcinogen (diethylnitrosamine, DEN)-initiated alcohol-promoted mouse model. In addition to reduced steatosis and inflammatory foci, TP abolished the presence of preneoplastic foci of altered hepatocytes in DEN-injected mice fed alcohol. These reductions were associated with decreased hepatic CYP2E1 protein levels, restored levels of peroxisome proliferator-activated receptor-α and downstream gene expression, decreased inflammatory gene expression, and reduced endoplasmic reticulum stress markers. These data provide strong evidence for TP as an effective whole food prevention strategy against ALD.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Citocromo P-450 CYP2E1/biosíntesis , Dieta , Etanol/efectos adversos , Extractos Vegetales/farmacología , Solanum lycopersicum/química , Animales , Peso Corporal/efectos de los fármacos , Carotenoides/metabolismo , Carotenoides/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Citocromo P-450 CYP2E1/metabolismo , Suplementos Dietéticos , Dietilaminas/toxicidad , Modelos Animales de Enfermedad , Estrés del Retículo Endoplásmico/efectos de los fármacos , Inducción Enzimática/efectos de los fármacos , Hígado Graso Alcohólico/tratamiento farmacológico , Hígado Graso Alcohólico/genética , Hígado Graso Alcohólico/metabolismo , Hígado Graso Alcohólico/patología , Regulación de la Expresión Génica/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Hepatocitos/patología , Hígado/efectos de los fármacos , Hígado/metabolismo , Licopeno , Ratones , PPAR alfa/genética , Extractos Vegetales/uso terapéutico , Polvos , RatasRESUMEN
Previous studies demonstrated that diet-induced obese mice fed a semi-purified high-fat diet (HFD) had greater liver tumorigenesis than mice fed a non-semi-purified diet. Because ingredients present in standard unpurified diets may elicit potential chemopreventive properties that are not present in semi-purified diets, the present study evaluated hepatic tumorigenic effects of dietary fat by replacing it with refined carbohydrates [digestible saccharides; high-carbohydrate diet (HCD)] in a semi-purified diet without altering other components. Two-wk-old C57Bl/6J male mice were randomly injected i.p. with either the liver-specific carcinogen diethylnitrosamine (25 mg/kg body weight) to induce liver cancer or saline as the nontumor control. At age 6 wk, mice with or without cancer initiation were further randomly assigned to an HFD (26% and 60% energy from carbohydrates and fat, respectively) or an HCD (66% and 12% energy from carbohydrates and fat, respectively) and consumed food ad libitum for 24 wk. Results showed that HCD-fed mice had a comparable degree of hepatic tumorigenesis (tumor number and volume) as HFD-fed mice, despite having significantly reduced body weights. HCD feeding induced greater hepatic endoplasmic reticulum (ER) stress-mediated protein kinase RNA-activated-like kinase (PERK) activation and oncogenic interleukin-6/signal transducer and activator of transcription 3 signaling than HFD feeding. HCD-stimulated PERK signaling was associated with elevated expression of prosurvival markers in tumors, including induced protein kinase B activation, increased extracellular signal-regulated kinases 1/2 phosphorylation, and elevated cyclin D1 protein expression. However, HCD-mediated PERK activation in tumors was also positively associated with markers of proapoptosis, which included elevated CCAAT/enhancer-binding protein homology protein expression and increased cleaved caspase-3. HCD-fed mice had greater severity in hepatic steatosis than HFD-fed mice. HCD-induced steatosis exacerbation was associated with increased expression in hepatic de novo lipogenic markers that can promote ER stress. Together, these data indicated that chronic HCD consumption by mice can produce comparable severity of hepatic tumorigenesis as HFD consumption, potentially through upregulating PERK-mediated ER stress.
Asunto(s)
Carcinoma Hepatocelular/metabolismo , Carbohidratos de la Dieta/farmacología , Grasas de la Dieta/farmacología , Hígado Graso/metabolismo , Neoplasias Hepáticas/metabolismo , Animales , Apoptosis/fisiología , Carcinógenos/farmacología , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/mortalidad , Dietilnitrosamina/farmacología , Modelos Animales de Enfermedad , Factor 2 Eucariótico de Iniciación/metabolismo , Hígado Graso/mortalidad , Hígado Graso/patología , Hepatitis/metabolismo , Hepatitis/mortalidad , Hepatitis/patología , Lipogénesis/fisiología , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/mortalidad , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Distribución Aleatoria , eIF-2 Quinasa/metabolismoRESUMEN
BACKGROUND: Aging and chronic alcohol consumption are both modifiers of DNA methylation, but it is not yet known whether chronic alcohol consumption also alters DNA hydroxymethylation, a newly discovered epigenetic mark produced by oxidation of methylcytosine. Furthermore, it has not been tested whether aging and alcohol interact to modify this epigenetic phenomenon, thereby having an independent effect on gene expression. METHODS: Old (18 months) and young (4 months) male C57BL/6 mice were pair-fed either a Lieber-DeCarli liquid diet with alcohol (18% of energy) or an isocaloric Lieber-DeCarli control diet for 5 weeks. Global DNA hydroxymethylation and DNA methylation were analyzed from hepatic DNA using a new liquid chromatography-tandem mass spectrometry method. Hepatic mRNA expression of the Tet enzymes were measured via quantitative real-time polymerase chain reaction. RESULTS: In young mice, mild chronic alcohol exposure significantly reduced global DNA hydroxymethylation compared with control mice (0.22 ± 0.01 vs. 0.29 ± 0.06%, p = 0.004). Alcohol did not significantly alter hydroxymethylcytosine levels in old mice. Old mice fed the control diet showed decreased global DNA hydroxymethylation compared with young mice fed the control diet (0.24 ± 0.02 vs. 0.29 ± 0.06%, p = 0.04). This model suggests an interaction between aging and alcohol in determining DNA hydroxymethylation (pinteraction = 0.009). Expression of Tet2 and Tet3 was decreased in the old mice relative to the young (p < 0.005). CONCLUSIONS: The observation that alcohol alters DNA hydroxymethylation indicates a new epigenetic effect of alcohol. This is the first study demonstrating the interactive effects of chronic alcohol consumption and aging on DNA hydroxymethylation.
Asunto(s)
Envejecimiento/genética , Consumo de Bebidas Alcohólicas/genética , Metilación de ADN/efectos de los fármacos , Etanol/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Animales , Citocromo P-450 CYP2E1/biosíntesis , Proteínas de Unión al ADN/biosíntesis , Dioxigenasas , Epigénesis Genética/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Proteínas Proto-Oncogénicas/biosíntesisRESUMEN
BACKGROUND: Stunting remains a major public health concern in Nepal as it increases the risk of illness, irreversible body damage and mortality in children. Public health planners can reshape and redesign new interventions to reduce stunting and severe stunting among children aged less than 5 years in this country by examining their determinants. Hence, this study identifies factors associated with stunting and severe stunting among children aged less than five years in Nepal. METHODS: The sample is made up of 2380 children aged 0 to 59 months with complete anthropometric measurements from the 2011 Nepal Demographic and Health Survey (NDHS). Simple and multiple logistic regression analyses were used to examine stunting and severe stunting against a set of variables. RESULTS: The prevalences of stunting and severe stunting were 26.3% [95% confidence Interval (CI): 22.8, 30.1] and 10.2% (95%CI: 7.9, 13.1) for children aged 0-23 months, respectively, and 40.6 (95%CI: 37.3, 43.2) and 15.9% (95%CI: 13.9, 18.3) for those aged 0-59 months, respectively. After adjusting for potential confounding factors, multivariable analyses showed that the most consistent significant risk factors for stunted and severely stunted children aged 0-23 and 0-59 months were household wealth index (poorest household), perceived size of baby (small babies) and breastfeeding for more than 12 months (adjusted odds ratio (AOR) for stunted children aged 0-23 months = 2.60 [95% CI: (1.87, 4.02)]; AOR for severely stunted children aged 0-23 months = 2.87 [95% CI: (1.54, 5.34)]; AOR for stunted children aged 0-59 months = 3.54 [95% CI: (2.41, 5.19)] and AOR for severely stunted children aged 0-59 months = 4.15 [95% CI: (2.45, 6.93)]. CONCLUSIONS: This study suggests that poorest households and prolonged breastfeeding (more than 12 months) led to increased risk of stunting and severe stunting among Nepalese children. However, community-based education intervention are needed to reduce preventable deaths triggered by malnutrition in Nepal and should target children born to mothers of low socioeconomic status.
Asunto(s)
Trastornos del Crecimiento/epidemiología , Adolescente , Adulto , Lactancia Materna , Preescolar , Parto Obstétrico/métodos , Femenino , Abastecimiento de Alimentos , Encuestas Epidemiológicas , Humanos , Lactante , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Masculino , Persona de Mediana Edad , Análisis Multivariante , Nepal/epidemiología , Pobreza , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Prior studies assessing the metabolic effects of different types of carbohydrates have focused on their glycaemic response. However, the response of postprandial cardiometabolic risk indicators has not been considered in these studies. The present study assessed postprandial lipid responses to two forms of carbohydrates used as reference foods for glycaemic index determinations, white bread (50 g available carbohydrate) and glucose (50 g), under controlled conditions and with intra-individual replicate determinations. A total of twenty adults (2070 years) underwent two cycles of challenges with each pair of reference foods (four challenges/person), administered in a random order on separate days under standard conditions. Serum lipids (total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG and NEFA), glucose and insulin were monitored for 5 h post-ingestion. Oral glucose resulted in greater glycaemic and insulinaemic responses than white bread for the first 90 min and a greater subsequent decline after 120 min (P =0·0001). The initial decline in serum NEFA concentrations was greater after the oral glucose than after the white bread challenge, as was the rebound after 150 min (P = 0·001). Nevertheless, the type of carbohydrate had no significant effect on postprandial total cholesterol, LDL-cholesterol and HDL-cholesterol concentrations. Following an initial modest rise in TAG concentrations in response to both challenges, the values dropped below the fasting values for oral glucose but not for the white bread challenge. These data suggest that the type of carbohydrate used to determine the glycaemic index, bread or glucose, has little or modest effects on postprandial plasma cholesterol concentrations. Differences in TAG and NEFA concentrations over the 5 h time period were modest, and their clinical relevance is unclear.
Asunto(s)
Pan , Enfermedades Cardiovasculares/etiología , Colesterol/sangre , Carbohidratos de la Dieta/metabolismo , Glucosa/metabolismo , Índice Glucémico , Lípidos/sangre , Adulto , Anciano , Glucemia/metabolismo , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/metabolismo , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Dieta , Carbohidratos de la Dieta/farmacología , Carbohidratos de la Dieta/normas , Ayuno , Ácidos Grasos no Esterificados/sangre , Femenino , Glucosa/farmacología , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , Periodo Posprandial , Valores de Referencia , Triglicéridos/sangre , Adulto JovenRESUMEN
The Dietary Guidelines for Americans 2010 provides authoritative advice on what Americans should eat to stay healthy. These guidelines provide a quantitative recommendation to consume 250 mg/d of (n-3) fatty acids (also known as omega-3 fatty acids). To achieve this goal, Americans would need to more than triple the amount of EPA and DHA currently consumed. This paper assessed the cost implications of increased levels of EPA and DHA from marine and nonmarine food sources using data from the 2007-2008 NHANES, USDA nutrient data base, and the USDA Center for the Nutrition Policy and Promotion food price data. Stearidonic acid (SDA)-enhanced soybean oil is a lower cost alternative to commonly consumed marine food as a source of EPA. In addition, given that SDA-enhanced soybean oil is intended to be used as an ingredient in a variety of products, this may enable consumers to increase consumption of EPA through commonly consumed foods.
Asunto(s)
Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-3/economía , Costos y Análisis de Costo , Suplementos Dietéticos/economía , Ingestión de Alimentos , Ácidos Grasos Omega-3/aislamiento & purificación , Humanos , Política Nutricional/economía , Alimentos Marinos/análisis , Alimentos Marinos/economía , Aceite de Soja/química , Aceite de Soja/economía , Estados UnidosRESUMEN
Linoleic acid (LA) and α-linolenic acid (ALA) are essential fatty acids that play an important role in modulation of T cell proliferation. The effects of consuming novel soybean oils varying in LA:ALA ratios on T cell proliferation and inflammatory responses were assessed in older adults. Eighteen participants (>50 y old) with elevated cholesterol concentrations (3.37-4.14 mmol/L LDL cholesterol) consumed 5 experimental diets in random order for periods of 35 d. Each diet contained 30% of energy as fat, two-thirds of which was high-oleic acid soybean oil (HiOleic-SO), soybean oil (SO), low-SFA soybean oil (LoSFA-SO), hydrogenated soybean oil (Hydrog-SO), or low-ALA soybean oil (LoALA-SO), resulting in LA:ALA ratios of 2.98, 8.70, 9.69, 15.2, and 18.3, respectively. Participants had higher proliferative responses to phytohemagglutinin (PHA) compared with baseline following consumption of SO (26%; P < 0.05), LoSFA-SO (22%; P < 0.05), or HiOleic-SO (24%; P < 0.05) diets. Proliferative response was similar to the baseline after participants consumed diets with an LA:ALA ratio >10 (Hydrog-SO and LoALA-SO). Post-diet intervention, LA:ALA ratios correlated with proliferative responses to PHA (r = -0.87; P = 0.05). An optimal proliferative response was observed at an LA:ALA ratio of 8.70, with an inverse correlation between proliferative response and LA:ALA ratios >8.70. These effects were independent of changes in the production of PGE(2), inflammatory cytokines, or cytokines involved in growth of lymphocytes. These data suggest that the LA:ALA ratio modulates the proliferative ability of T lymphocytes, which may be due to subtle changes in fatty acid composition of the phospholipids in immune cells.
Asunto(s)
Hipercolesterolemia/inmunología , Ácido Linoleico/administración & dosificación , Activación de Linfocitos , Aceite de Soja/administración & dosificación , Linfocitos T/inmunología , Ácido alfa-Linolénico/administración & dosificación , Proteína C-Reactiva/análisis , HDL-Colesterol/sangre , Citocinas/biosíntesis , Dinoprostona/biosíntesis , Método Doble Ciego , Femenino , Humanos , Hipercolesterolemia/sangre , Ácido Linoleico/análisis , Masculino , Persona de Mediana Edad , Fosfolípidos/sangre , Aceite de Soja/análisis , Ácido alfa-Linolénico/análisisRESUMEN
BACKGROUND: Nutrition transition towards a Western diet is happening in parallel with the rapidly increasing rates of cardiovascular disease and its risk factors in Kuwait. The cardiometabolic deaths attributable to poor diet have not been quantified among Kuwaiti adults. METHODS: Using a Comparative Risk Assessment model that incorporated dietary intake data from Kuwait's first national nutrition survey, number of cardiometabolic deaths from the World Health Organization, and estimated associations of diet with cardiometabolic deaths from the Global Burden of Disease project, we estimated the number and proportion of cardiometabolic deaths attributable to suboptimal intake of 10 dietary factors among Kuwaiti adults ages 25+ years, and by population subgroups. FINDINGS: An estimated 1,308 (95% uncertainty interval [UI] = 1,228-1,485) cardiometabolic deaths were attributed to suboptimal diet, accounting for 64.7% (95% UI = 60.7%-73.4%) of all cardiometabolic deaths in Kuwait in 2009. The low intake of nuts/seeds was associated with the highest estimated number and proportion of cardiometabolic deaths (n = 380, 18.8%), followed by high intake of sodium (n = 256, 12.6%), low intake of fruits (n = 250, 12.4%), low intake of vegetables (n = 236, 11.7%), low intake of whole grains (n = 201, 9.9%), and high intake of sugar-sweetened beverages (n = 201, 9.9%). The estimated proportions of cardiometabolic deaths attributable to suboptimal diet were higher in men (67.7%) than women (57.8%) and in younger adults aged 25-34 years (84.5%) than older adults aged ≥55 years (55.6%). CONCLUSION: Suboptimal dietary intake was associated with a very substantial proportion of cardiometabolic deaths among Kuwaiti adults in 2009, with young adults and men experiencing the largest proportion of diet-associated cardiometabolic deaths in Kuwait.
Asunto(s)
Enfermedades Cardiovasculares , Dieta , Masculino , Adulto Joven , Femenino , Humanos , Anciano , Kuwait/epidemiología , Verduras , Encuestas Nutricionales , Enfermedades Cardiovasculares/etiología , Factores de RiesgoRESUMEN
The current nutrition situation in Malawi, characterized by high rates of malnutrition in communities and hospitals and a rapidly increasing burden of overweight/obesity and diet-related noncommunicable diseases, highlights the urgent need for registered dietitians, who have a proven track record in the prevention and management of all forms of malnutrition and improving patient outcomes. However, dietetics practice has been described as underdeveloped and fragmented in many parts of Africa, exacerbated by a severe and chronic shortage of dietetics professionals and a lack of nutrition and dietetic education programs in most African countries.We share early lessons learned in the development and implementation of the first dietetics program in Malawi. Within 6 years, the program produced 10 graduate dietitians who have filled the first clinical dietitian posts in Malawian public hospitals. This early success can be attributed to the model used to develop and implement the program, which included early stakeholder engagement to define the priority skills and competencies of a Malawian dietitian, the use of internationally recognized training standards, and the development of strategic institutional partnerships that brought together complementary skills and expertise. Furthermore, using existing resources and recruiting students with a nutrition and health background accelerated implementation. The current dietetics curriculum responds to the national nutrition and health policy direction and strategic objectives. Early and sustained government engagement was crucial in creating demand and securing career prospects for graduates. Although still in its infancy, dietitians in Malawi are poised to contribute significantly to alleviating the country's complex nutrition challenges.
Asunto(s)
Dietética , Nutricionistas , Creación de Capacidad , Dietética/educación , Humanos , Malaui , Estado Nutricional , Nutricionistas/educaciónRESUMEN
Cigarette smoke (CS) is an independent risk factor in development of nonalcoholic steatohepatitis (NASH) and fibrosis. Lycopene, a carotenoid naturally occurring in tomatoes, has been shown to be a protective agent against tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced NASH. In the present study using a ferret model we investigated whether CS promotes NASH and whether dietary lycopene can inhibit CS-promoted NASH development, and if so, what potential mechanisms were involved. Ferrets were divided into 4 groups (n=12-16/group): control, NNK/CS exposed, NNK/CS plus low-dose lycopene (2.2 mg/kg BW/day), and NNK/CS plus high-dose lycopene (6.6 mg/kg BW/day) groups, for 26 weeks. Results showed that hepatic steatosis, infiltrates of inflammatory cells, and the number and size of inflammatory foci in liver, together with key genes involved in hepatic fibrogenesis were higher in the NNK/CS group compared to the control group; a lycopene diet reversed these changes to the levels of the control group. Interestingly, a major lycopene cleavage enzyme, beta-carotene 9',10'-oxygenase (BCO2), which recently has been recognized to play metabolic roles beyond cleavage function, was down-regulated by NNK/CS exposure, but this decrease was prevented by lycopene feeding. NNK/CS exposure also downregulated liver expression of antioxidant enzymes and upregulated oxidative stress marker, which were all prevented by lycopene. In conclusion, our results suggest that CS can promote development of NASH and liver fibrosis in ferrets, which is associated with downregulation of BCO2 and impairment of antioxidant system in liver; dietary lycopene may inhibit CS-promoted NASH by preventing suppression of BCO2 and decline in antioxidant network.