Adult rats sired by obese fathers present learning deficits associated with epigenetic and neurochemical alterations linked to impaired brain glutamatergic signaling.

AIM: Offspring of obese mothers are at high risk of developing metabolic syndrome and cognitive disabilities. Impaired metabolism has also been reported in the offspring of obese fathers. However, whether brain function can also be affected by paternal obesity has barely been examined. This study aimed to characterize the learning deficits resulting from paternal obesity versus those induced by maternal obesity and to identify the underlying mechanisms. METHODS: Founder control and obese female and male Wistar rats were mated to constitute three first-generation (F1) experimental groups: control mother/control father, obese mother/control father, and obese father/control mother. All F1 animals were weaned onto standard chow and underwent a learning test at 4 months of age, after which several markers of glutamate-mediated synaptic plasticity together with the expression of miRNAs targeting glutamate receptors and the concentration of kynurenic and quinolinic acids were quantified in the hippocampus and frontal cortex. RESULTS: Maternal obesity induced a severe learning deficit by impairing memory encoding and memory consolidation. The offspring of obese fathers also showed reduced memory encoding but not impaired long-term memory formation. Memory deficits in offspring of obese fathers and obese mothers were associated with a down-regulation of genes encoding NMDA glutamate receptors subunits and several learning-related genes along with impaired expression of miR-296 and miR-146b and increased concentration of kynurenic acid. CONCLUSION: Paternal and maternal obesity impair offspring's learning abilities by affecting different processes of memory formation. These cognitive deficits are associated with epigenetic and neurochemical alterations leading to impaired glutamate-mediated synaptic plasticity.

Obesity-Induced Memory Deficits in Female Rats Are Oestrous Cycle Dependent and Linked to Impaired Brain Kynurenine Pathway Metabolism.

INTRODUCTION: Obesity is associated with impaired learning, but the mechanisms underlying this cognitive dysfunction are poorly understood. Moreover, whether obesity-induced learning deficits show sexual dimorphism remains controversial. Females are believed to be protected from cognitive decline by oestrogens. These hormones enhance the expression of tryptophan hydroxylase 2, the rate-limiting enzyme in the transformation of tryptophan (Trp) into serotonin which plays a significant role in learning and memory. However, several learning-regulating compounds also arise from Trp metabolism through the kynurenine pathway (KP), including kynurenic acid (KA), xanthurenic acid (XA), and NAD+. The present study aimed to determine the involvement of the KP of Trp metabolism in the regulation of learning in control and obese female rats. METHODS: The learning capabilities of control and obese rats were evaluated using the novel object recognition test. Trp and Trp-derived metabolites were quantified in the hippocampus and frontal cortex by ultra-performance liquid chromatography-tandem mass spectrometry. RESULTS: Control rats in proestrus/oestrous performed better than their control mates in metestrus/dioestrus. Likewise, while control and obese rats in dioestrus/metestrus did not show differences in learning, obese rats in proestrus/oestrous displayed decreased memory capacity along with decreased Trp concentration and reduced KA, XA, and NAD+ production in the hippocampus. These neurochemical alterations were associated with impaired expression of mRNAs coding for key enzymes of the KP. CONCLUSION: The results presented here indicate that the deleterious effects of obesity on learning are closely related to the oestrous cycle and associated with an impairment of the KP of Trp metabolism.

Maternal Stress during Pregnancy in Mice Induces Sex-Dependent Behavioral Alterations in Offspring along with Impaired Serotonin and Kynurenine Pathways of Tryptophan Metabolism.

Maternal stress during pregnancy results in increased risk of developing psychiatric disorders in the offspring including anxiety, depression, schizophrenia, and autism. However, the mechanisms underlying this disease susceptibility remain largely to be determined. In this study, the involvement of the serotonin (5-HT) and kynurenine (KYN) pathways of tryptophan metabolism on the behavioral deficits induced by maternal stress during the late phase of gestation in mice was investigated. Adult offspring born to control or restraint-stressed dams were exposed to the elevated plus-maze and tail suspension tests. Metabolites of the KYN and 5-HT pathways were measured in the hippocampus and brainstem by ultra-performance liquid chromatography tandem mass spectrometry. Female, but not male, prenatally stressed (PNS) offspring displayed a depressive-like phenotype, mainly when in proestrus/diestrus, along with reduced hippocampal 5-HT levels and high 5-HT turnover rate in the hippocampus and brainstem. In contrast, male PNS mice showed enhanced anxiety-like behaviors and higher hippocampal and brainstem quinolinic acid levels compared to male offspring born to nonstressed dams. These results indicate that maternal stress affects the behavior and brain metabolism of tryptophan in the offspring in a sex-dependent manner and suggest that alterations in both the 5-HT and KYN pathways may underlie the emotional dysfunctions observed in individuals exposed to stress during in utero development.

Learning Deficits Induced by High-Calorie Feeding in the Rat are Associated With Impaired Brain Kynurenine Pathway Metabolism.

In addition to be a primary risk factor for type 2 diabetes and cardiovascular disease, obesity is associated with learning disabilities. Here we examined whether a dysregulation of the kynurenine pathway (KP) of tryptophan (Trp) metabolism might underlie the learning deficits exhibited by obese individuals. The KP is initiated by the enzymatic conversion of Trp into kynurenine (KYN) by indoleamine 2,3-dioxygenase (IDO). KYN is further converted to several signaling molecules including quinolinic acid (QA) which has a negative impact on learning. Wistar rats were fed either standard chow or made obese by exposure to a free choice high-fat high-sugar (fcHFHS) diet. Their learning capacities were evaluated using a combination of the novel object recognition and the novel object location tasks, and the concentrations of Trp and KYN-derived metabolites in several brain regions determined by ultra-performance liquid chromatography-tandem mass spectrometry. Male, but not female, obese rats exhibited reduced learning capacity characterized by impaired encoding along with increased hippocampal concentrations of QA, Xanthurenic acid (XA), Nicotinamide (Nam), and oxidized Nicotinamide Adenine Dinucleotide (NAD+). In contrast, no differences were detected in the serum levels of Trp or KP metabolites. Moreover, obesity enhanced the expression in the hippocampus and frontal cortex of kynurenine monooxygenase (KMO), an enzyme involved in the production of QA from kynurenine. QA stimulates the glutamatergic system and its increased production leads to cognitive impairment. These results suggest that the deleterious effects of obesity on cognition are sex dependent and that altered KP metabolism might contribute to obesity-associated learning disabilities.

Adult rats from undernourished dams show sex-dependent impaired expression in taste papillae and hypothalamus of genes responsible for sweet and fat detection and signalling.

AIM: Individuals undernourished in utero or during early life are at high risk of developing obesity and metabolic disorders and show an increased preference for consuming sugary and fatty food. This study aimed at determining whether impaired taste detection and signalling in the lingual epithelium and the brain might contribute to this altered pattern of food intake. METHODS: The preference for feeding fat and sweet food and the expression in circumvallate papillae and hypothalamus of genes coding for sweet and fat receptors and transducing pathways were evaluated in adult rats born to control or calorie-restricted dams. Expression in the hypothalamus and the brain's reward system of genes involved in the homeostatic and hedonic control of food intake was also determined. RESULTS: Male and female undernourished animals exhibited increased expression in taste papillae and hypothalamus of T1R1, T1R2, CD36, gustducin, TRMP5 and PLC-ß2 genes, all of which modulate sweet and fat detection and intracellular signalling. However, the severity of the effect was greater in females than in males. Moreover, male, but not female, undernourished rats consumed more standard and sweetened food than their control counterparts and presented increased hypothalamic AgRP and NPY mRNAs levels together with enhanced dopamine transporter and dopamine receptor D2 expression in the ventral tegmental area. CONCLUSIONS: Maternal undernutrition induces sex-specific changes in food preferences and gene expression in taste papillae, hypothalamus and brain reward regions. The gene expression alterations in the male offspring are in line with their preference for consuming sugary and fatty food.

DHA Supplementation of Obese Rats throughout Pregnancy and Lactation Modifies Milk Composition and Anxiety Behavior of Offspring.

We investigated if supplementing obese mothers (MO) with docosahexaenoic acid (DHA) improves milk long-chain polyunsaturated fatty acid (LCPUFA) composition and offspring anxiety behavior. From weaning throughout pregnancy and lactation, female Wistar rats ate chow (C) or a high-fat diet (MO). One month before mating and through lactation, half the mothers received 400 mg DHA kg-1 d-1 orally (C+DHA or MO+DHA). Offspring ate C after weaning. Maternal weight, total body fat, milk hormones, and milk nutrient composition were determined. Pups' milk nutrient intake was evaluated, and behavioral anxiety tests were conducted. MO exhibited increased weight and total fat, and higher milk corticosterone, leptin, linoleic, and arachidonic acid (AA) concentrations, and less DHA content. MO male and female offspring had higher ω-6/ ω-3 milk consumption ratios. In the elevated plus maze, female but not male MO offspring exhibited more anxiety. MO+DHA mothers exhibited lower weight, total fat, milk leptin, and AA concentrations, and enhanced milk DHA. MO+DHA offspring had a lower ω-6/ω-3 milk intake ratio and reduced anxiety vs. MO. DHA content was greater in C+DHA milk vs. C. Supplementing MO mothers with DHA improves milk composition, especially LCPUFA content and ω-6/ω-3 ratio reducing offspring anxiety in a sex-dependent manner.

Maternal DHA Supplementation during Pregnancy and Lactation in the Rat Protects the Offspring against High-Calorie Diet-Induced Hepatic Steatosis.

Maternal supplementation during pregnancy with docosahexaenoic acid (DHA) is internationally recommended to avoid postpartum maternal depression in the mother and improve cognitive and neurological outcomes in the offspring. This study was aimed at determining whether this nutritional intervention, in the rat, protects the offspring against the development of obesity and its associated metabolic disorders. Pregnant Wistar rats received an extract of fish oil enriched in DHA or saline (SAL) as placebo by mouth from the beginning of gestation to the end of lactation. At weaning, pups were fed standard chow or a free-choice, high-fat, high-sugar (fc-HFHS) diet. Compared to animals fed standard chow, rats exposed to the fc-HFHS diet exhibited increased body weight, liver weight, body fat and leptin in serum independently of saline or DHA maternal supplementation. Nevertheless, maternal DHA supplementation prevented both the glucose intolerance and the rise in serum insulin resulting from consumption of the fc-HFHS diet. In addition, animals from the DHA-fc-HFHS diet group showed decreased hepatic triglyceride accumulation compared to SAL-fc-HFHS rats. The beneficial effects on glucose homeostasis declined with age in male rats. Yet, the preventive action against hepatic steatosis was still present in 6-month-old animals of both sexes and was associated with decreased hepatic expression of lipogenic genes. The results of the present work show that maternal DHA supplementation during pregnancy programs a healthy phenotype into the offspring that was protective against the deleterious effects of an obesogenic diet.

Indicadores socioeconómicos de obesidad materna. El estudio de una cohorte en Morelos, México / Socioeconomic indicators of maternal obesity. Study of a cohort in Morelos, México / Indicadores socioeconómicos da obesidade materna. Estudo de uma coorte no Morelos, México / Indicateurs socio-économiques de l'obésité maternelle. Étude d'une cohorte au Morelos, Mexique

Resumen: Objetivo: Identificar y analizar desde una perspectiva cuanti/cualitativita los indicadores socioeconómicos de la obesidad materna en México. Material y métodos: Investigación evaluativa basada en un diseño de cohorte de tipo prospectivo/descriptivo. El tamaño de la muestra se conformó por todas las mujeres que llegaron a consulta prenatal a partir de la semana 24 de gestación en un hospital de referencia estatal. El tamaño de la muestra se estimó con un 80% de poder y 95% de confianza y significancia. Los indicadores de interés fueron aspectos socioeconómicos, alimentación, antropometría, dieta, seguridad alimentaria y actividad física. El análisis cuantitativo se realizó utilizando el software Stata versión 14 y el análisis cualitativo con Atlas-ti versión 8.0. Resultados: La cohorte estuvo conformada por 402 mujeres embarazadas en 2017. De los resultados principales encontramos que el 55% de las mujeres se encontraba en el rango de edad de 18-24 años; el 15% de las mujeres refirió contar con un empleo remunerado; el 42% de la población tenía secundaria completa; el 32.1% presentó un grado de inseguridad alimentaria; la media de IMC fue de 27.8±4.8, el 48% de las mujeres presentaron sobrepeso y obesidad. Conclusiones: Los resultados cuantitativos sugieren que poblaciones con mayor vulnerabilidad socio-económica, inseguridad alimentaria y escasa actividad física, son más propensas a la obesidad materna. Los resultados cualitativos, además de complementar y reforzar los resultados cuantitativos, plantean evidencias para identificar a mayor detalle las barreras y facilitadores para fortalecer programas de intervención en la prevención de la obesidad materna.

Abstract; Objective: To identify and analyze from a quantitative / qualitative perspective the socioeconomic indicators of maternal obesity in Mexico. Methods and material: Evaluative research based on a prospective / analytical cohort design. The sample size was established by all the women who came to the antenatal clinic from the 24th week of gestation in a state referral hospital. The sample size was estimated with 80% power and 95% confidence and significance. The indicators of interest were socioeconomic aspects, nutrition, anthropometry, diet, food safety and physical activity. The quantitative analysis was performed using the Stata version 14 software and the qualitative analysis with Atlas-ti version 8.0. Results: The cohort was comprised of 402 pregnant women in 2017. From the main results we found that 55% of the women were in the age range of 18-24 years; 15% of women reported having a paid job; 42% of the population had full secondary education; 32.1% presented a degree of food insecurity; the mean BMI was 27.8 ± 4.8, 48% of the women were overweight and obese. Conclusions: Quantitative results suggest that populations with greater socio-economic vulnerability, food insecurity and low physical activity are more prone to maternal obesity. The qualitative results, besides complementing and reinforcing the quantitative results, present evidence to identify in greater detail the barriers and facilitators to strengthen intervention programs in the prevention of maternal obesity.

Resumo: Objetivo: Identificar e analisar, de uma perspectiva quantitativa / qualitativa, os indicadores socioeconômicos da obesidade materna no México. Materiais e métodos: Pesquisa avaliativa baseada em um desenho de coorte prospectivo / analítico. O tamanho da amostra foi estabelecido por todas as mulheres que chegaram à clínica pré-natal a partir da 24a semana de gestação em um hospital estadual de referência. O tamanho da amostra foi estimado com 80% de poder e 95% de confiança e significância. Os indicadores de interesse foram aspectos socioeconómicos, nutrição, antropometria, dieta, segurança alimentar e atividade física. A análise quantitativa foi realizada utilizando o software Stata versão 14 e a análise qualitativa com Atlas-ti versão 8.0. Resultados: A coorte foi composta por 402 gestantes em 2017. Dos principais resultados, constatou-se que 55% das mulheres encontravam- se na faixa etária de 18 a 24 anos; 15% das mulheres relataram ter um emprego remunerado; 42% da população tinha ensino secundário completo; 32,1% apresentaram grau de insegurança alimentar; a média do IMC foi de 27,8 ± 4,8, 48% das mulheres estavam acima do peso e obesas. Conclusões: Os resultados quantitativos sugerem que populações com maior vulnerabilidade socioeconómica, insegurança alimentar e baixa atividade física são mais propensas à obesidade materna. Os resultados qualitativos, além de complementar e reforjar os resultados quantitativos, apresentam evidencias para identificar em maior detalhe as barreiras e facilitadores para fortalecer os programas de intervenção na prevenção da obesidade materna.

Résumé: Objectif: Identifier et analyser d'un point de vue quantitatif / qualitatif les indicateurs socio-économiques de l'obésité maternelle au Mexique. Matériel et méthodes: Recherche évaluative basée sur une conception de cohorte prospective / analytique. La taille de l'échantillon a été établie par toutes les femmes qui sont venues á la clinique prénatale á partir de la 24e semaine de gestation dans un hópital de référence. La taille de l'échantillon a été estimée avec 80% de puissance et 95% de confiance et de signification. Les indicateurs d'intéret étaient les aspects socio-économiques, la nutrition, l'anthropométrie, l'alimentation, la sécurité alimentaire et l'activité physique. L'analyse quantitative a été réalisée á l'aide du logiciel Stata version 14 et de l'analyse qualitative avec Atlas-ti version 8.0. Résultats: La cohorte était composée de 402 femmes enceintes en 2017. D'aprés les principaux résultats, nous avons constaté que 55% des femmes étaient agées de 18 á 24 ans; 15% des femmes ont déclaré avoir un travail rémunéré; 42% de la population ont fait des études secondaires complétes; 32,1% présentaient un degré d'insécurité alimentaire; l'IMC moyen était de 27,8 ± 4,8, 48% des femmes étaient en surpoids et obéses. Conclusions: Les résultats quantitatifs suggérent que les populations ayant une plus grande vulnérabilité socio-économique, l'insécurité alimentaire et une faible activité physique sont plus sujettes á l'obésité maternelle. Les résultats qualitatifs, en plus de compléter et de renforcer les résultats quantitatifs, présentent des preuves pour identifier plus en détail les obstacles et les facilitateurs pour renforcer les programmes d'intervention dans la prévention de l'obésité maternelle.

Socio-economic indicators, dietary patterns, and physical activity as determinants of maternal obesity in middle-income countries: Evidences from a cohort study in Mexico.

Maternal obesity is one of the main public health problems at a world level. It is a multifactorial disease with multiple causes, and few studies exist on its dietary patterns, physical activity and social determinants. This work aims to identify determinants of maternal obesity in a middle income country. Research is based on a prospective cohort design. Data were collected using questionnaires applied to pregnant women. Three dietary patterns were identified, and only half of the women carry out physical activity. The regression analysis showed an association between overweight/obesity and the following variables: age 25 to 29 years old (3.8; CI 1.6-9.0), 30 to 34 years old (3.7; CI 1.2-11.6); health problems during pregnancy (2.1; CI 1.0-4.1); socio-economic income (1.73; CI 1.54-2.05); hypertension (2.7; CI 1.4-4.5); mild food insecurity (1.9; CI 1.0-3.8); moderate insecurity (3.7; CI 0.92-15.4); refined food dietary pattern (.76; CI.61-.95). The risk of increasing BMI during pregnancy mainly depends on socioeconomic and demographic variables such as age, educational level, income, food insecurity, and dietary pattern. This study's results could be used as evidences for the revision, planning, and adjustment of interventions for the prevention and management of maternal obesity, as a part of the national strategies against overweight and obesity.

Maternal obesity leads to long-term altered levels of plasma ceramides in the offspring as revealed by a longitudinal lipidomic study in children.

BACKGROUND/OBJECTIVES: Maternal obesity is associated with increased risk of obesity and other symptoms of the metabolic syndrome in the offspring. Nevertheless, the molecular mechanisms and cellular factors underlying this enhanced disease susceptibility remain to be determined. Here, we aimed at identifying changes in plasma lipids in offspring of obese mothers that might underpin, and serve as early biomarkers of, their enhanced metabolic disease risk. SUBJECTS/METHODS: We performed a longitudinal lipidomic profiling in plasma samples from normal weight, overweight, and obese pregnant women and their children that participated in the Prenatal Omega-3 Fatty Acid Supplementation, Growth, and Development trial conducted in Mexico. At recruitment women were aged between 18 and 35 years and in week 18-22 of pregnancy. Blood samples were collected at term delivery by venipuncture from mothers and from the umbilical cord of their newborns and from the same infants at 4 years old under non-fasting conditions. Lipidomic profiling was done using ultra-performance liquid chromatography high-resolution mass spectrometry. RESULTS: Analysis of the lipidomic data showed that overweight and obese mothers exhibited a significant reduction in the total abundance of ceramides (Cer) in plasma, mainly of Cer (d18:1/20:0), Cer (d18:1/22:0), Cer (d18:1/23:0), and Cer (d18:1/24:0), compared with mothers of normal body weight. This reduction was confirmed by the direct quantification of these and other ceramide species. Similar quantitative differences in the plasma concentration of Cer (d18:1/22:0), Cer (d18:1/23:0), and Cer (d18:1/24:0), were also found between 4-year-old children of overweight and obese mothers compared with children of mothers of normal body weight. Noteworthy, children exhibited equal daily amounts of energy and food intake independently of the BMI of their mothers. CONCLUSIONS: Maternal obesity results in long-lasting changes in plasma ceramides in the offspring suggesting that these lipids might be used as early predictors of metabolic disease risk due to maternal obesity.

[Socioeconomic determinants of maternal obesity in Mexico and France. Comparative analysis of two cohorts]. / Indicadores socioeconómicos de la obesidad materna en México y Francia. Análisis comparado de dos cohortes.

OBJECTIVE: To identify and analyze the socioeconomic indicators of maternal obesity in Mexico and France. MATERIAL AND METHODS: Comparative study of two cohorts: EDEN (France) and NUTTSEA (Mexico). The study population consisted of women who requested prenatal consultation at week 24 of pregnancy. Data were collected using questionnaires and semi-structured interviews. The variables of interest were socioeconomic aspects, nutrition, anthropometry and food security. The quantitative analysis was performed using Stata and the qualitative analysis with Atlas-ti. RESULTS: In the EDEN cohort, 68.6% were aged 25-34 years, 73% had paid employment and 53% completed high school. In addition, 6.6% reported having difficulty accessing food and the mean gestational BMI was 23.23 ± 4.6. In the NUTTSEA cohort, 55% were in the age range 18-24 years, 15% reported having paid employment, 42% had completed secondary education, 32.1% presented a degree of food insecurity, and the mean BMI was 27.8 ± 4.8. CONCLUSIONS: The qualitative and quantitative results of both cohorts suggest that populations with greater socio-economic vulnerability are more prone to maternal obesity, which leads to determine guidelines on barriers and facilitators to strengthen programs to prevent it maternal obesity.

OBJETIVO: Identificar y analizar los indicadores socioeconómicos de obesidad materna en México y Francia. METODOLOGÍA: Estudio comparativo de dos cohortes EDEN sus siglas en francés (Etude des déterminants pré et post natals précoces de la santé et de développement de l'enfant) (Francia) y NUTTSEA (México). La población de estudio se conformó por mujeres que solicitaron consulta prenatal en semana 24 de gestación. Los datos fueron recolectados con cuestionarios y entrevistas semi-estructuradas. Las variables de interés fueron aspectos socioeconómicos, alimentación, antropometría y seguridad alimentaria. El análisis cuantitativo se realizó utilizando Stata y el análisis cualitativo con Atlas-ti. RESULTADOS: En cohorte EDEN el 68.6% resultó con edad de 25-34 años, el 73% tenían un empleo remunerado, el 53% preparatoria completa; el 6.6% refirió tener dificultad para acceder a los alimentos; la media del IMC gestacional fue de 23.23±4.6. En la cohorte NUTTSEA el 55% se encontraba en el rango de edad de 18-24 años; el 15% refirió contar con un empleo remunerado; el 42% de la población tenía secundaria completa; el 32.1% presentó un grado de inseguridad alimentaria; la media de IMC fue de 27.8±4.8. CONCLUSIONES: Los resultados cuali-cuantitativos de ambas cohortes sugieren que poblaciones con mayor vulnerabilidad socio-económica son más propensas a la obesidad materna, determinando directrices sobre barreras y facilitadores para fortalecer programas de prevención de la obesidad materna.

Indicadores socioeconómicos de la obesidad materna en México y Francia: análisis comparado de dos cohortes / Socioeconomic determinants of maternal obesity in Mexico and France: comparative analysis of two cohorts

RESUMEN Objetivo Identificar y analizar los indicadores socioeconómicos de obesidad materna en México y Francia. Metodología Estudio comparativo de dos cohortes EDEN sus siglas en francés (Etude des déterminants pré et post natals précoces de la santé et de développement de l'enfant) (Francia) y NUTTSEA (México). La población de estudio se conformó por mujeres que solicitaron consulta prenatal en semana 24 de gestación. Los datos fueron recolectados con cuestionarios y entrevistas semi-estructuradas. Las variables de interés fueron aspectos socioeconómicos, alimentación, antropometría y seguridad alimentaria. El análisis cuantitativo se realizó utilizando Stata y el análisis cualitativo con Atlas-ti. Resultados En cohorte EDEN el 68.6% resultó con edad de 25-34 años, el 73% tenían un empleo remunerado, el 53% preparatoria completa; el 6.6% refirió tener dificultad para acceder a los alimentos; la media del IMC gestacional fue de 23.23±4.6. En la cohorte NUTTSEA el 55% se encontraba en el rango de edad de 18-24 años; el 15% refirió contar con un empleo remunerado; el 42% de la población tenía secundaria completa; el 32.1% presentó un grado de inseguridad alimentaria; la media de IMC fue de 27.8±4.8. Conclusiones Los resultados cuali-cuantitativos de ambas cohortes sugieren que poblaciones con mayor vulnerabilidad socio-económica son más propensas a la obesidad materna, determinando directrices sobre barreras y facilitadores para fortalecer programas de prevención de la obesidad materna.(AU)

ABSTRACT Objective To identify and analyze the socioeconomic indicators of maternal obesity in Mexico and France. Material and Methods Comparative study of two cohorts: EDEN (France) and NUTTSEA (Mexico). The study population consisted of women who requested prenatal consultation at week 24 of pregnancy. Data were collected using questionnaires and semi-structured interviews. The variables of interest were socioeconomic aspects, nutrition, anthropometry and food security. The quantitative analysis was performed using Stata and the qualitative analysis with Atlas-ti. Results In the EDEN cohort, 68.6% were aged 25-34 years, 73% had paid employment and 53% completed high school. In addition, 6.6% reported having difficulty accessing food and the mean gestational BMI was 23.23 ± 4.6. In the NUTTSEA cohort, 55% were in the age range 18-24 years, 15% reported having paid employment, 42% had completed secondary education, 32.1% presented a degree of food insecurity, and the mean BMI was 27.8 ± 4.8. Conclusions The qualitative and quantitative results of both cohorts suggest that populations with greater socio-economic vulnerability are more prone to maternal obesity, which leads to determine guidelines on barriers and facilitators to strengthen programs to prevent it maternal obesity.(AU)

Abnormality of adipokines and endothelial dysfunction in Mexican obese adolescents with insulin resistance.

PURPOSE: The aim of this study was to investigate the possible relationship among insulin resistance (IR), endothelial dysfunction, and alteration of adipokines in Mexican obese adolescents and their association with metabolic syndrome (MetS). MATERIALS AND METHODS: Two hundred and twenty-seven adolescents were classified according to the body mass index (BMI) (control: N=104; obese: N=123) and homeostasis model of the assessment-insulin resistance index (HOMA-IR) (obese with IR: N=65). The circulating concentrations of leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), and IR were determined by standard methods. RESULTS: The obese adolescents with IR presented increased presence of MetS and higher circulating concentrations in sICAM-1 in comparison with the obese subjects without IR. The lowest concentrations of adiponectin were observed in the obese with IR. In multivariate linear regression models, sICAM-1 along with triglycerides, total cholesterol, and waist circumference was strongly associated with HOMA-IR (R2=0.457, P=0.008). Similarly, after adjustment for age, BMI-SDS, lipids, and adipokines, HOMA-IR remained associated with sICAM-1 (R2=0.372, P=0.008). BMI-SDS was mildly associated with leptin (R2=0.176, P=0.002) and the waist circumference was mild and independent determinant of adiponectin (R2=0.136, P=0.007). CONCLUSIONS: Our findings demonstrated that the obese adolescents, particularly the obese subjects with IR exhibited increased presence of MetS, abnormality of adipokines, and endothelial dysfunction. The significant interaction between IR and endothelial dysfunction may suggest a novel therapeutic approach to prevent or delay systemic IR and the genesis of cardiovascular diseases in obese patients.

Maternal protein restriction during gestation and lactation in the rat results in increased brain levels of kynurenine and kynurenic acid in their adult offspring.

Early malnutrition is a risk factor for depression and schizophrenia. Since the offspring of malnourished dams exhibit increased brain levels of serotonin (5-HT), a tryptophan-derived neurotransmitter involved in the pathophysiology of these mental disorders, it is believed that the deleterious effects of early malnutrition on brain function are due in large part to altered serotoninergic neurotransmission resulting from impaired tryptophan (Trp) metabolism. However, tryptophan is also metabolized through the kynurenine (KYN) pathway yielding several neuroactive compounds including kynurenic (KA), quinolinic (QA) and xanthurenic (XA) acids. Nevertheless, the impact of perinatal malnutrition on brain kynurenine pathway metabolism has not been examined to date. Here, we used ultra-performance liquid chromatography-tandem mass spectrometry for the simultaneous quantification of tryptophan and a set of seven compounds spanning its metabolism through the serotonin and kynurenine pathways, in the brain of embryos and adult offspring of rat dams fed a protein-restricted (PR) diet. Protein-restricted embryos showed reduced brain levels of Trp, serotonin and KA, but not of KYN, XA, or QA. In contrast, PR adult rats exhibited enhanced levels of Trp in the brainstem and cortex along with increased concentrations of 5-HT, kynurenine and XA. The levels of XA and KA were also increased in the hippocampus of adult PR rats. These results show that early protein deficiency induces selective and long-lasting changes in brain kynurenine metabolism. Given the regulatory role of KYN pathway metabolites on brain development and function, these changes might contribute to the risk of developing psychiatric disorders induced by early malnutrition.

Paternal selenium deficiency but not supplementation during preconception alters mammary gland development and 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis in female rat offspring.

Breast cancer is a global public health problem and accumulating evidence indicates early-life exposures as relevant factors in the disease risk determination. Recent studies have shown that paternal nutrition can influence offspring health including breast cancer risk. Selenium is a micronutrient with essential role in central aspects of embryogenesis, male fertility and cancer and that has been extensively studied as a chemopreventive agent in several breast cancer experimental models. Thus, we designed an animal study to evaluate whether paternal selenium deficiency or supplementation during preconception could affect the female offspring mammary gland development and breast cancer susceptibility. Male Sprague-Dawley rats were fed AIN93-G diet containing 0.15 ppm (control diet), 0.05 ppm (deficient diet) or 1 ppm (supplemented diet) of selenium for 9 weeks and mated with control female rats. Mammary carcinogenesis was induced with 7,12-dimethylbenz[a]anthracene (DMBA) in their female offspring. Paternal selenium deficiency increased the number of terminal end buds, epithelial elongation and cell proliferation in the mammary gland of the female rat offspring and these effects were associated with higher susceptibility to DMBA-induced mammary tumors (increased incidence and higher grade tumors). On the other hand, paternal selenium supplementation did not influence any of these parameters. These results highlight the importance of father's nutrition including selenium status as a relevant factor affecting daughter's breast cancer risk and paternal preconception as a potential developmental stage to start disease preventive strategies.

[The new paradigm of the developmental origin of health and diseases (DOHaD)--Epigenetics and environment: evidence and missing links]. / Le nouveau paradigme de l'origine développementale de la santé et des maladies (DOHaD)--Épigénétique, environnement: preuves et chaînons manquants.

According to the new paradigm of the Developpemental Origins of Health and Disease (DOHaD), the environmental factors to which an individual is exposed throughout his life can leave an epigenetic footprint on the genome. A crucial period is the early development, where the epigenome is particularly sensitive to the effects of the environment, and during which the individual builds up his health capital that will enable him to respond more or less well to the vagaries of life. The research challenge is to decipher the modes of action and the epigenetic mechanisms put into play by environmental factors that lead to increased disease susceptibility or resilience. The challenge for health is to translate these scientific discoveries into action through, among others, the establishment of preventive recommendations to slow down the growing incidence of non communicable diseases.

[Epigenetics in transgenerational responses to environmental impacts: from facts and gaps]. / Épigénétique et réponses transgénérationnelles aux impacts de l'environnement--Des faits aux lacunes.

The existence of non-genetic and non-cultural mechanisms that transfer information on the memory of parental exposures to various environments, determining the reactivity of the following generations to their environments during their life, are of growing interest. Yet fundamental questions remain about the nature, the roles and relative importance of epigenetic marks and processes, non-coding RNAs, or other mechanisms, and their persistence over generations. A model incorporating the various transmission systems, their cross-talks and windows of susceptibility to the environment as a function of sex/gender of parent and offspring, has yet to be built.

[The sensory and nutritional experience of parents guide offsprings' feeding behavior]. / L'expérience sensorielle et nutritionnelle des parents et leur état métabolique orientent le comportement alimentaire de leur descendance.

Eating behavior is strongly regulated by intrinsic physiological factors and largely influenced by the individual and cultural environments. Excessive food intake and sedentary lifestyle are the main reasons for the global epidemic of obesity. The influence of family background on eating habits makes no doubt but the fact that the nutritional, metabolic and hormonal status of the parents before conception, and of the mother during gestation and lactation, may influence the child's future eating behavior is an innovative concept that opens the way for preventive policies. In the last decades, research on human cohorts and animal models have targeted biological mechanisms (neuroanatomical, epigenetic) that give some clues on how eating behavior can be formatted by early nutrition and related sensory experience.

Can early protein restriction induce the development of binge eating?

We tested the hypothesis that perinatal undernourishment is a factor for binge eating. At 52 days rats born from dams fed on 17% protein (Control) or 8% protein (Undernourished) were distributed into four groups, two of which continued to be fed ad libitum chow and two were submitted to three consecutive Restricted/Refeeding (R/R) cycles. According to the following schedule: Control Naïve (from mothers fed 17% protein/no restriction phase); Control Restricted (from mothers fed 17% protein/restriction phase); Undernourished Naïve (from mothers fed 8% protein/no restriction phase); and Undernourished Restricted (from mothers fed 8% protein/restriction phase). Each cycle consisted of a restriction phase (in the first four days 40% of the mean daily individual chow intake was offered for consumption), followed by a refeeding phase (4 days of chow ad libitum). After the three cycles, all animals were subjected to a feeding test (chow diet and palatable food ad libitum for 24h). During the feeding test, the Undernourished Restricted demonstrated rebound hyperphagia during 2, 4 and 6h. These results suggest the perinatal undernourishment cannot contribute to a binge eating phenotype.

Early malnutrition results in long-lasting impairments in pattern-separation for overlapping novel object and novel location memories and reduced hippocampal neurogenesis.

Numerous epidemiological studies indicate that malnutrition during in utero development and/or childhood induces long-lasting learning disabilities and enhanced susceptibility to develop psychiatric disorders. However, animal studies aimed to address this question have yielded inconsistent results due to the use of learning tasks involving negative or positive reinforces that interfere with the enduring changes in emotional reactivity and motivation produced by in utero and neonatal malnutrition. Consequently, the mechanisms underlying the learning deficits associated with malnutrition in early life remain unknown. Here we implemented a behavioural paradigm based on the combination of the novel object recognition and the novel object location tasks to define the impact of early protein-restriction on the behavioural, cellular and molecular basis of memory processing. Adult rats born to dams fed a low-protein diet during pregnancy and lactation, exhibited impaired encoding and consolidation of memory resulting from impaired pattern separation. This learning deficit was associated with reduced production of newly born hippocampal neurons and down regulation of BDNF gene expression. These data sustain the existence of a causal relationship between early malnutrition and impaired learning in adulthood and show that decreased adult neurogenesis is associated to the cognitive deficits induced by childhood exposure to poor nutrition.