Neonatal inhibition of androgen activity alters the programming of body weight and orexinergic peptides differentially in male and female rats.

The involvement of androgens in the regulation of energy metabolism has been demonstrated. The main objective of the present research was to study the involvement of androgens in both the programming of energy metabolism and the regulatory peptides associated with feeding. For this purpose, androgen receptors and the main metabolic pathways of testosterone were inhibited during the first five days of postnatal life in male and female Wistar rats. Pups received a daily s.c. injection from the day of birth, postnatal day (P) 1, to P5 of Flutamide (a competitive inhibitor of androgen receptors), Letrozole (an aromatase inhibitor), Finasteride (a 5-alpha-reductase inhibitor) or vehicle. Body weight, food intake and fat pads were measured. Moreover, hypothalamic Agouti-related peptide (AgRP), neuropeptide Y (NPY), orexin, and proopiomelanocortin (POMC) were analyzed by quantitative real-time polymerase chain reaction assay. The inhibition of androgenic activity during the first five days of life produced a significant decrease in body weight in females at P90 but did not affect this parameter in males. Moreover, the inhibition of aromatase decreased hypothalamic AgRP mRNA levels in males while the inhibition of 5α-reductase decreased hypothalamic AgRP and orexin mRNA levels in female rats. Finally, food intake and visceral fat, but not subcutaneous fat, were affected in both males and females depending on which testosterone metabolic pathway was inhibited. Our results highlight the differential involvement of androgens in the programming of energy metabolism as well as the AgRP and orexin systems during development in male and female rats.

Influencia del consumo de hidratos de carbono sobre el estado oxidante en mujeres con y sin diabetes mellitus gestacional / Influence of carbohydrate intake on oxidative status among women with and without gestational diabetes mellitus

RESUMEN Objetivo: Identificar la influencia del consumo de hidratos de carbono (HCO) sobre el estado oxidante en mujeres con y sin diabetes mellitus gestacional (DMG). Materiales y métodos: Se realizó un estudio transversal, observacional y comparativo a dos grupos de 21 mujeres con y sin DMG, respectivamente, en la ciudad de Toluca, México, de enero a diciembre del 2022. Para evaluar parámetros sociodemográficos, se les aplicó un cuestionario de historia clínica; en cuanto a los parámetros antropométricos, se les midió peso corporal y estatura; y respecto a los parámetros bioquímicos, colesterol total (CT) y triglicéridos (TG). Para evaluar el estado oxidante/antioxidante se cuantificaron, como marcador oxidante, el malondihaldeído (MDA), y como antioxidantes, catalasa (cat), superóxido dismutasa (SOD) y capacidad antioxidante total (CAT). Los hábitos dietéticos se evaluaron a través de un recordatorio de 24 horas, en ambos grupos de mujeres, para obtener los macronutrientes: proteínas, lípidos e HCO. A partir de los hidratos de carbono totales (HCOT), se calcularon los hidratos de carbono complejos (HCOC) e hidratos de carbono simples (HCOS) como la sacarosa. Para el cálculo de HCOS por día, se usó la lista de alimentos con contenido de sacarosa por cada 100 gramos de consumo que emplea el Sistema Mexicano de Equivalentes; para el análisis de dieta, se utilizó el programa Nutrikcal VO. Se usaron las pruebas estadísticas t de Student para muestras independientes, U de Mann-Whitney para las variables no homogéneas y se realizó la correlación de Spearman (p < 0,05) en el programa SPSS, versión 19. Resultados: Los resultados mostraron que la diferencia entre los valores de CT (p < 0,029), TG (p < 0,029), las enzimas: cat (p < 0,011), SOD (p < 0,013), así como el MDA (p < 0,039), fueron significativamente mayores en las pacientes del grupo con DMG en comparación con el grupo sin DMG. Además, el grupo con DMG consumió mayor proporción de sacarosa. Conclusiones: Las mujeres con DMG tienen un desequilibrio en el estado oxidante/antioxidante influenciado por el tipo de HCO que consumen, en particular los HCOS como la sacarosa.

ABSTRACT Objective: To identify the influence of carbohydrate (CHO) intake on oxidative status among women with and without gestational diabetes mellitus (GDM). Materials and methods: A cross-sectional, observational and comparative study was carried out with two groups of 21 women each with and without GDM in the city of Toluca, Mexico, from January to December 2022. The sociodemographic parameters were determined by administering the patients a medical history questionnaire; anthropometric parameters such as body weight and height were measured; and biochemical parameters including total cholesterol (TC) and triglycerides (TG) were calculated. The oxidant/antioxidant status was assessed as follows: malondialdehyde (MDA) as oxidative stress marker; and catalase (CAT), superoxide dismutase (SOD) and total antioxidant capacity (TAC) as antioxidants. Dietary habits were evaluated through a 24-hour reminder in both groups of women to obtain the macronutrient classes, i.e., proteins, fats and CHOs. Based on the total carbohydrates (TCHOs), complex (CCHOs) and simple carbohydrates (SCHOs) such as sucrose were calculated. SCHOs per day were measured using the list of foods with sucrose content per 100 grams according to the Mexican Food Equivalence System (SMAE). The NutriKcal VO program was used for the dietary analysis. Statistical tests such as Student's t test and Mann-Whitney U test were performed for the independent samples and nonhomogeneous variables, respectively, and Spearman's rank correlation coefficient (p < 0.05) was determined using the IBM SPSS Statistics V19. Results: The results showed that the difference between the levels of TC (p < 0.029), TG (p < 0.029), enzymes CAT (p < 0.011) and SOD (p < 0.013), as well as MDA (p < 0.039) was significantly higher among patients in the group with GDM compared to that in the group without GDM. In addition, the group with GDM consumed a higher proportion of sucrose. Conclusions: Women with GDM have an imbalance in the oxidant/antioxidant status, influenced by the type of CHO they consume, particularly SCHOs such as sucrose.

Genistein early in life modifies the arcuate nucleus of the hypothalamus morphology differentially in male and female rats.

In the present work we analyzed the effects of postnatal exposure to two doses of genistein (10 µg/g or 50 µg/g) from postnatal (P) day 6 to P13, on the morphology of the arcuate nucleus (Arc). The analyses of Arc coronal brain sections at 90 days showed that the ArcMP had higher values in volume, Nissl-stained neurons and GPER-ir neurons in males than in females and the treatment with genistein abolished these sex differences in most of the parameters studied. Moreover, in males, but not in females, the GPER-ir neurons decreased in the ArcMP but increased in the ArcL with both doses of genistein. In the ArcLP, GPER-ir population increased with the lowest doses and decreased with the highest one in males. Our results confirm that the Arc subdivisions have differential vulnerability to the effects of genistein during development, depending on which neuromorphological parameters, dose and sex are analyzed.

Activity-based anorexia alters hypothalamic POMC and orexin populations in male rats.

The objective of this study was to investigate the orexin and POMC populations in the hypothalamic nuclei of male Wistar rats after the activity-based anorexia (ABA) procedure. Four groups were established based on food restriction and activity: activity (A), ABA, diet (D) and control (C). The ABA protocol consisted of free access to a running wheel for a period of 22 h and access to food for 1 h. When the animals in the ABA group reached the ABA criterion, were sacrificed, and their brains were collected and serially sectioned. The free-floating sections were processed for orexin and POMC immunostaining. The number of orexin A-ir cells in the perifornical-dorsomedial-hypothalamus continuum (PFD) and lateral hypothalamus (LH) and the number of POMC-ir cells in the arcuate nucleus (Arc) were estimated. Data on food intake, body weight and wheel turns were also analyzed. The ABA procedure caused a significant decrease in body weight along with a significant increase in activity. Moreover, at the end of the ABA procedure, the number of POMC-ir cells decreased in the Arc in the A group, and significantly more in the ABA group, and the number of orexin A-ir positive cells decreased in the LH in D and ABA groups. The differential decrease in POMC in the ABA group emphasizes the importance of the melanocortin system in the maintenance of ABA, but more research is needed to elucidate the involvement of this peptide in the mechanism that promotes and maintains anorexia nervosa and how increased activity may interact with all these processes.

The Effect of Dietary Patterns on Inflammatory Biomarkers in Adults with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Some evidence supports the fact that chronic low-grade inflammation contributes to the physiopathology of type 2 diabetes mellitus (T2DM), and circulating markers of inflammation (e.g., C-reactive protein (CRP), pro- and anti-inflammatory biomarkers (e.g., adiponectin), and endothelial function markers could indicate an ongoing pathology. Following certain dietary patterns (DPs) may result in favorable changes in inflammatory biomarkers. The overarching aim of this systematic review and meta-analysis is to explore the inflammatory effect of healthy DPs on inflammatory biomarkers in adults with T2DM. A systematic search of the literature was conducted using the electronic databases MEDLINE, SCOPUS, and Cochrane Central Register of Controlled Trials. A total of 10 randomized controlled clinical trials (RCTs) were analyzed. In our linear meta-analysis, the random-effects model was applied to estimate standardized mean differences (SMD) to associate the effect of the interventions. Dietary Approaches to Stop Hypertension (DASH), Diabetes UK healthy eating, Mediterranean Diet (MD), Diabetes Prevention Program (DPP), and the American Heart Association's Therapeutic Lifestyle Changes diet were associated with a significant reduction in CRP (SMD: −0.83, 99% CI −1.49, −0.17, p < 0.001; I2 94%), while plasma levels of adiponectin were significantly higher with the intake of MD, DPP, and Diabetes UK healthy eating (SMD: 0.81, 99% CI 0.06,1.56, p < 0.005; I2 96%), both of which indicate less inflammation. Sensitivity analyses were carried out, and potential publication bias was examined. In conclusion, low- moderate-quality evidence from RCTs suggests that, for the DPs evaluated, there are favorable changes in CRP and adiponectin.

Influence of early maternal separation on susceptibility to the activity-based anorexia model in male and female Sprague Dawley rats.

A principal animal paradigm employed in Anorexia Nervosa (AN) study is the activity-based anorexia (ABA) model. The model's efficacy in recapitulating the core features of AN in humans allows for the study of the parameters involved in the disorder. The current study examined the susceptibility to the ABA protocol in the presence of a significant stressor (maternal separation) in male and female Sprague Dawley rats. More importantly, we analysed the sex-differences on activity levels during different periods of the ABA protocol to determine the period(s) influencing the most pathological weight loss. Both components of the ABA protocol contributed to the subjects' bodyweight loss. Stress in the first two weeks of development conferred a protective effect in males. Time spent and activity levels on the running wheel were higher in females compared to males. Hyperactivity in ABA subjects was observed during the food-anticipatory activity (FAA) and postprandial activity in males and during the FAA and nocturnal activity periods in females. This study aids in understanding the effect of intensity of activity during specific periods on the pathological weight loss in ABA rats. These observations are informative for therapies aimed at ameliorating body mass index in AN patients.

Prenatal Low-Protein and Low-Calorie Diets Differentially Alter Arcuate Nucleus Morphology in Newborn Male Rats.

Background: Malnutrition during the early stages of development produces alterations that can compromise the functioning of the hypothalamic circuits that regulate food intake. The purpose of this study is to analyze the effects that a low-protein and low-calorie diet has on the morphology of the arcuate nucleus (ARC) of the hypothalamus in newborn male and female rats. Methods: On gestational day 6 (G6), six pregnant rats were divided into two groups. One group was made up of three pregnant rats, which were fed ad libitum with a control diet (20% casein), and the other one was made up of three pregnant rats, which were fed ad libitum with a low-protein diet (8% casein) and 30% of a calorie-restricted diet. On the day of birth, pups were sacrificed, resulting in four experimental groups: control male, control female, low-protein and low-calorie diet male, and low-protein and low-calorie diet female (n = 5 in each group). The volume and number of neurons, together with the neuronal density and number of apoptotic cells, were measured. Results: Males on a low-protein and low-calorie diet showed a significant increase in the number of neurons and in the neuronal density of the ARC with regard to the rest of the groups studied. These increases were also reflected in the posterior part of the nucleus. Although the existence of sexual dimorphism was not detected in any of the parameters studied in the control groups, the number of neurons and neuronal density showed differences between males and females fed with a low-protein and low-calorie diets due to the increase in the number of neurons shown by the male. No significant differences were found in the number of apoptotic cells. Conclusion: Our results show that a low-protein and low-calorie diet during the prenatal stage produces alterations in the ARC of the hypothalamus in newborn animals and, more importantly, that the effects of malnutrition are evident in males but not in females. Therefore, it is essential to follow a balanced diet during the early stages of life to ensure optimal development of the neural circuits that regulate eating.

Organizational Effects of Estrogens and Androgens on Estrogen and Androgen Receptor Expression in Pituitary and Adrenal Glands in Adult Male and Female Rats.

Sex steroid hormones, such as androgens and estrogens, are known to exert organizational action at perinatal periods and activational effects during adulthood on the brain and peripheral tissues. These organizational effects are essential for the establishment of biological axes responsible for regulating behaviors, such as reproduction, stress, and emotional responses. Estradiol (E2), testosterone, and their metabolites exert their biological action through genomic and non-genomic mechanisms, bounding to canonical receptors, such as estrogen receptor (ER)α, ERß, and androgen receptor (AR) or membrane receptors, such as the G protein-coupled estrogen receptor (GPER), respectively. Expression of ERs and AR was found to be different between males and females both in the brain and peripheral tissues, suggesting a sex-dependent regulation of their expression and function. Therefore, studying the ERs and AR distribution and expression levels is key to understand the central and peripheral role of sex steroids in the establishment of sex-specific behaviors in males and females. We investigated the organizational effects of estrogens and androgens in the pituitary and adrenal glands of adult male and female rats. For this, selective blockade of AR with flutamide or 5α-reductase with finasteride or aromatase with letrozole during the first 5 days of life has been performed in male and female pups and then quantification of ERs and AR expression in both glands has been carried out in adulthood. Data show that inhibition of dihydrotestosterone (DHT) and E2 production during the first five postnatal days mainly decreases the ER expression in male to female values and AR expression in female to male levels in the pituitary gland and increases AR expression in female to male levels in the adrenal gland. In contrast, blocking the action of androgens differentially modulates the ERs in males and females and decreases AR in both males and females in both glands. Altogether, the results suggest that neonatal modifications of the androgen and estrogen pathways can potentially lead to permanent modifications of the neuroendocrine functions of the pituitary and adrenal glands in the adulthood of both sexes.

Changes in Metabolic Regulation and the Microbiota Composition after Supplementation with Different Fatty Acids in db/db Mice.

INTRODUCTION: The effects of fatty acids on health vary and depend on the type, amount, and route of consumption. EPA and DHA have a defined role in health, unlike coconut oil. OBJECTIVE: The aim was to investigate the changes in metabolic regulation and the composition of the culture-dependent microbiota after supplementation with different fatty acids in db/db mice. Material and Methods. We were using 32 8-week-old db/db mice, supplemented for eight weeks with EPA/DHA derived from microalgae as well as coconut oil. The lipid, hormonal profiles, and composition of the culture-dependent microbiota and the phylogenetic analysis based on the 16S rRNA gene sequencing were determined for identification of the intestinal microbiota. RESULTS: Enriched diet with EPA/DHA reduced TNF-α, C-peptide, insulin resistance, resistin, and the plasma atherogenic index, but increased TC, LDL-c, VLDL-c, and TG without changes in HDL-c. Coconut oil raised the HDL-c, GIP, and TNF-α, with TG, insulin resistance, adiponectin, and C-peptide reduced. CONCLUSION: The most abundant microbial populations were Firmicutes and the least Proteobacteria. EPA/DHA derived from microalgae contributes to improving the systemic inflammatory status, but depressed the diversity of the small intestine microbiota. Coconut oil only decreased the C-peptide, raising TNF-α, with an unfavorable hormonal and lipid profile.

Mordeduras de perro. Análisis epidemiológico (2011-2018) y estrategias preventivas / Dog bites. Epidemiological analysis (2011-2018) and preventive strategies

Introducción: las mordeduras de perro en niños constituyen una causa importante de morbimortalidad a nivel mundial. El objetivo de este estudio es describir características epidemiológicas y clínicas de estos incidentes en pacientes pediátricos de nuestro entorno, así como aportar medidas de prevención para disminuir la incidencia. Material y métodos: estudio retrospectivo a partir de pacientes atendidos por mordedura de perro durante un periodo de nueve años en un hospital de tercer nivel. Se recogieron variables demográficas, raza de perro, localización de lesiones, relación entre perro y niño, tratamiento recibido y secuelas. Resultados: se registraron 236 pacientes, con una edad media de siete años. La mayoría de las agresiones se produjeron en los meses de primavera y verano. En el 76% de los casos el perro era conocido. Solo el 10% de los ataques fueron por perros considerados peligrosos. El 51% de las lesiones se localizaron en la cabeza y el cuello y el 40% en las extremidades. Se indicó profilaxis antibiótica en el 90%. Un 5% requirió ingreso. Se describieron secuelas estéticas y psicológicas en un 15% y 10%, respectivamente. Conclusiones: las mordeduras de perro siguen siendo un motivo de consulta en urgencias pediátricas, siendo los menores de seis años los más afectados. El perro agresor es en la mayoría de los casos del entorno familiar y de raza considerada no peligrosa. La persistencia de estos incidentes debe hacer adoptar medidas preventivas que ayuden a concienciar a la población y así disminuir la frecuencia y gravedad de estas lesiones (AU)

Introduction: dog bites in children continue to cause significant morbidity and mortality worldwide. The purpose of our study was to describe the epidemiological and clinical characteristics of these accidents in the paediatric population of our area and to propose preventive strategies to reduce their incidence. Material and methods: we conducted a retrospective study of patients that received care for dog bites in a tertiary care hospital over an 8-year period. We collected data on demographic variables, dog breeds, sites of injury, the relationship between the dog and the child, the treatment received and sequelae. Results: we identified 236 patients, with a mean age of 7 years. Most attacks occurred in spring or summer. In 76% of cases, the child was acquainted with the dog. Only 10% of attacks involved breeds considered potentially dangerous. Fifty-one percent of injuries were in the head or neck and 40% in the extremities. Antibiotic prophylaxis was prescribed in 90% of cases. Five percent required admission. Cosmetic sequelae were documented in 15% of patients and psychological sequelae in 10%. Conclusions: dog bites continue to be a reason for seeking emergency care in the paediatric population, and they are most frequent in children aged less than 6 years. In most cases, the attacking dog was a family pet of a breed not considered dangerous. The persistence of these incidents calls for the implementation of preventive measures to raise awareness in the population and thus reduce the frequency and severity of these injuries (AU)

Chronic consumption of sweeteners in mice and its effect on the immune system and the small intestine microbiota / Consumo crónico de edulcorantes en ratones y su efecto sobre el sistema inmunitario y la microbiota del intestino delgado

Introduction: Sweeteners are additives used in different foods. They can be natural (sucrose and stevia) or artificial (sucralose). Currently, they are routinely consumed in multiple products and their effects on the mucosa of the small intestine and its microbiota are still controversial. Objective: To relate the consumption of sweeteners and their effect on the immune system and the microbiota of the small intestine in CD1 mice. Materials and methods: We used 54 three-week-old CD1 mice divided into three groups in the experiments: 1) A group of three weeks without treatment, 2) a group treated for six weeks, and 3) a group treated for 12 weeks using sucrose, sucralose, and stevia. We obtained CD19+ B lymphocytes, IgA+ antibodies, transforming growth factor-beta (TGF-b), and interleukins 12 and 17 (IL-12 and -17) from Peyer's patches and lamina propria cells while DNA was obtained from intestinal solids to identify bacterial species. Results: After 12 weeks, sucrose and sucralose consumption caused a reduction in bacterial communities with an increase in CD19+, a decrease in IgA+ and TGF-b, and an increase in IL-12 and -17 in the Peyer's patches while in the lamina propria there was an increase in all parameters. In contrast, stevia led to an improvement in bacterial diversity and percentage of CD19+ lymphocytes with minimal increase in IgA+, TGF-b, and IL-12, and a decrease in IL-17. Conclusion: Sucrose and sucralose caused negative alterations in bacterial diversity and immune parameters after 12 weeks; in contrast, stevia was beneficial for the intestinal mucosa.

Introducción. Los edulcorantes son aditivos que se consumen en los alimentos. Pueden ser naturales (sacarosa y estevia) o artificiales (sucralosa). Actualmente, se consumen rutinariamente en múltiples productos, y sus efectos en la mucosa y la microbiota del intestino delgado aún son controversiales Objetivo. Relacionar el consumo de edulcorantes y su efecto en el sistema inmunitario y la microbiota del intestino delgado en ratones CD1. Materiales y métodos. Se utilizaron 54 ratones CD1 de tres semanas de edad divididos en tres grupos: un grupo de tres semanas sin tratamiento, un grupo tratado durante seis semanas y un grupo tratado durante 12 semanas. Se les administró sacarosa, sucralosa y estevia. A partir del intestino delgado, se obtuvieron linfocitos B CD19+ y células IgA+, TGF-ß (Transforming Growth Factor-beta) o el factor de crecimiento transformador beta (TGF-beta), IL-12 e IL-17 de las placas de Peyer y de la lámina propia. De los sólidos intestinales se obtuvo el ADN para identificar las especies bacterianas. Resultados. Después del consumo de sacarosa y sucralosa durante 12 semanas, se redujeron las comunidades bacterianas, la IgA+ y el TGF-beta, se aumentó el CD19+, y además, se incrementaron la IL-12 y la IL-17 en las placas de Peyer; en la lámina propia, aumentaron todos estos valores. En cambio, con la estevia mejoraron la diversidad bacteriana y el porcentaje de linfocitos CD19+, y hubo poco incremento de IgA+, TGF-b e IL-17, pero con disminución de la IL-17. Conclusión. La sacarosa y la sucralosa alteraron negativamente la diversidad bacteriana y los parámetros inmunitarios después de 12 semanas, en contraste con la estevia que resultó benéfica para la mucosa intestinal.

Consumo crónico de edulcorantes en ratones y su efecto sobre el sistema inmunitario y la microbiota del intestino delgado / Chronic consumption of sweeteners in mice and its effect on the immune system and the small intestine microbiota

Resumen Introducción. Los edulcorantes son aditivos que se consumen en los alimentos. Pueden ser naturales (sacarosa y estevia) o artificiales (sucralosa). Actualmente, se consumen rutinariamente en múltiples productos, y sus efectos en la mucosa y la microbiota del intestino delgado aún son controversiales. Objetivo. Relacionar el consumo de edulcorantes y su efecto en el sistema inmunitario y la microbiota del intestino delgado en ratones CD1. Materiales y métodos. Se utilizaron 54 ratones CD1 de tres semanas de edad divididos en tres grupos: un grupo de tres semanas sin tratamiento, un grupo tratado durante seis semanas y un grupo tratado durante 12 semanas. Se les administró sacarosa, sucralosa y estevia. A partir del intestino delgado, se obtuvieron linfocitos B CD19+ y células IgA+, TGF-ß (Transforming Growth Factor-beta) o el factor de crecimiento transformador beta (TGF-beta), IL-12 e IL-17 de las placas de Peyer y de la lámina propia. De los sólidos intestinales se obtuvo el ADN para identificar las especies bacterianas. Resultados. Después del consumo de sacarosa y sucralosa durante 12 semanas, se redujeron las comunidades bacterianas, la IgA+ y el TGF-beta, se aumentó el CD19+, y además, se incrementaron la IL-12 y la IL-17 en las placas de Peyer; en la lámina propia, aumentaron todos estos valores. En cambio, con la estevia mejoraron la diversidad bacteriana y el porcentaje de linfocitos CD19+, y hubo poco incremento de IgA+, TGF-ß e IL-17, pero con disminución de la IL-17. Conclusión. La sacarosa y la sucralosa alteraron negativamente la diversidad bacteriana y los parámetros inmunitarios después de 12 semanas, en contraste con la estevia que resultó benéfica para la mucosa intestinal.

Abstract Introduction: Sweeteners are additives used in different foods. They can be natural (sucrose and stevia) or artificial (sucralose). Currently, they are routinely consumed in multiple products and their effects on the mucosa of the small intestine and its microbiota are still controversial. Objective: To relate the consumption of sweeteners and their effect on the immune system and the microbiota of the small intestine in CD1 mice. Materials and methods: We used 54 three-week-old CD1 mice divided into three groups in the experiments: 1) A group of three weeks without treatment, 2) a group treated for six weeks, and 3) a group treated for 12 weeks using sucrose, sucralose, and stevia. We obtained CD19+ B lymphocytes, IgA+ antibodies, transforming growth factor-beta (TGF-b), and interleukins 12 and 17 (IL-12 and -17) from Peyer's patches and lamina propria cells while DNA was obtained from intestinal solids to identify bacterial species. Results: After 12 weeks, sucrose and sucralose consumption caused a reduction in bacterial communities with an increase in CD19+, a decrease in IgA+ and TGF-b, and an increase in IL-12 and -17 in the Peyer's patches while in the lamina propria there was an increase in all parameters. In contrast, stevia led to an improvement in bacterial diversity and percentage of CD19+ lymphocytes with minimal increase in IgA+, TGF-b, and IL-12, and a decrease in IL-17. Conclusion: Sucrose and sucralose caused negative alterations in bacterial diversity and immune parameters after 12 weeks; in contrast, stevia was beneficial for the intestinal mucosa.

Relationship between Prenatal or Postnatal Exposure to Pesticides and Obesity: A Systematic Review.

In recent years, the worldwide prevalence of overweight and obesity among adults and children has dramatically increased. The conventional model regarding the onset of obesity is based on an imbalance between energy intake and expenditure. However, other possible environmental factors involved, such as the exposure to chemicals like pesticides, cannot be discarded. These compounds could act as endocrine-disrupting chemicals (EDC) that may interfere with hormone activity related to several mechanisms involved in body weight control. The main objective of this study was to systematically review the data provided in the scientific literature for a possible association between prenatal and postnatal exposure to pesticides and obesity in offspring. A total of 25 human and 9 animal studies were analyzed. The prenatal, perinatal, and postnatal exposure to organophosphate, organochlorine, pyrethroid, neonicotinoid, and carbamate, as well as a combined pesticide exposure was reviewed. This systematic review reveals that the effects of pesticide exposure on body weight are mostly inconclusive, finding conflicting results in both humans and experimental animals. The outcomes reviewed are dependent on many factors, including dosage and route of administration, species, sex, and treatment duration. More research is needed to effectively evaluate the impact of the combined effects of different pesticides on human health.

Relationship between Autism Spectrum Disorder and Pesticides: A Systematic Review of Human and Preclinical Models.

Autism spectrum disorder (ASD) is a complex set of neurodevelopmental pathologies characterized by impoverished social and communicative abilities and stereotyped behaviors. Although its genetic basis is unquestionable, the involvement of environmental factors such as exposure to pesticides has also been proposed. Despite the systematic analyses of this relationship in humans, there are no specific reviews including both human and preclinical models. The present systematic review summarizes, analyzes, and discusses recent advances in preclinical and epidemiological studies. We included 45 human and 16 preclinical studies. These studies focused on Organophosphates (OP), Organochlorine (OC), Pyrethroid (PT), Neonicotinoid (NN), Carbamate (CM), and mixed exposures. Preclinical studies, where the OP Chlorpyrifos (CPF) compound is the one most studied, pointed to an association between gestational exposure and increased ASD-like behaviors, although the data are inconclusive with regard to other ages or pesticides. Studies in humans focused on prenatal exposure to OP and OC agents, and report cognitive and behavioral alterations related to ASD symptomatology. The results of both suggest that gestational exposure to certain OP agents could be linked to the clinical signs of ASD. Future experimental studies should focus on extending the analysis of ASD-like behaviors in preclinical models and include exposure patterns similar to those observed in human studies.

Genistein during Development Alters Differentially the Expression of POMC in Male and Female Rats.

Phytoestrogens are considered beneficial for health, but some studies have shown that they may cause adverse effects. This study investigated the effects of genistein administration during the second week of life on energy metabolism and on the circuits regulating food intake. Two different genistein doses, 10 or 50 µg/g, were administered to male and female rats from postnatal day (P) 6 to P13. Physiological parameters, such as body weight and caloric intake, were then analyzed at P90. Moreover, proopiomelanocortin (POMC) expression in the arcuate nucleus (Arc) and orexin expression in the dorsomedial hypothalamus (DMH), perifornical area (PF) and lateral hypothalamus (LH) were studied. Our results showed a delay in the emergence of sex differences in the body weight in the groups with higher genistein doses. Furthermore, a significant decrease in the number of POMC-immunoreactive (POMC-ir) cells in the Arc in the two groups of females treated with genistein was observed. In contrast, no alteration in orexin expression was detected in any of the structures analyzed in either males or females. In conclusion, genistein can modulate estradiol's programming actions on the hypothalamic feeding circuits differentially in male and female rats during development.

G Protein-Coupled Estrogen Receptor Immunoreactivity in the Rat Hypothalamus Is Widely Distributed in Neurons, Astrocytes, and Oligodendrocytes, Fluctuates during the Estrous Cycle, and Is Sexually Dimorphic.

INTRODUCTION: The membrane-associated G protein-coupled estrogen receptor 1 (GPER) mediates the regulation by estradiol of arginine-vasopressin immunoreactivity in the supraoptic and paraventricular hypothalamic nuclei of female rats and is involved in the estrogenic control of hypothalamic regulated functions, such as food intake, sexual receptivity, and lordosis behavior. OBJECTIVE: To assess GPER distribution in the rat hypothalamus. METHODS: GPER immunoreactivity was assessed in different anatomical subdivisions of five selected hypothalamic regions of young adult male and cycling female rats: the arcuate nucleus, the lateral hypothalamus, the paraventricular nucleus, the supraoptic nucleus, and the ventromedial hypothalamic nucleus. GPER immunoreactivity was colocalized with NeuN as a marker of mature neurons, GFAP as a marker of astrocytes, and CC1 as a marker of mature oligodendrocytes. RESULTS: GPER immunoreactivity was detected in hypothalamic neurons, astrocytes, and oligodendrocytes. Sex and regional differences and changes during the estrous cycle were detected in the total number of GPER-immunoreactive cells and in the proportion of neurons, astrocytes, and oligodendrocytes that were GPER-immunoreactive. CONCLUSIONS: These findings suggest that estrogenic regulation of hypothalamic function through GPER may be different in males and females and may fluctuate during the estrous cycle in females.

G Protein-Coupled Estrogen Receptor Immunoreactivity Fluctuates During the Estrous Cycle and Show Sex Differences in the Amygdala and Dorsal Hippocampus.

G protein-coupled estrogen receptor (GPER) in the amygdala and the dorsal hippocampus mediates actions of estradiol on anxiety, social recognition and spatial memory. In addition, GPER participates in the estrogenic regulation of synaptic function in the amygdala and in the process of adult neurogenesis in the dentate gyrus. While the distribution of the canonical estrogen receptors α and ß in the amygdala and dorsal hippocampus are well characterized, little is known about the regional distribution of GPER in these brain regions and whether this distribution is affected by sex or the stages of the estrous cycle. In this study we performed a morphometric analysis of GPER immunoreactivity in the posterodorsal medial, anteroventral medial, basolateral, basomedial and central subdivisions of the amygdala and in all the histological layers of CA1 and the dentate gyrus of the dorsal hippocampal formation. The number of GPER immunoreactive cells was estimated in these different structures. GPER immunoreactivity was detected in all the assessed subdivisions of the amygdaloid nucleus and dorsal hippocampal formation. The number of GPER immunoreactive cells was higher in males than in estrus females in the central (P = 0.001) and the posterodorsal medial amygdala (P < 0.05); higher in males than in diestrus females in the strata orients (P < 0.01) and radiatum-lacunosum-moleculare (P < 0.05) of CA1-CA3 and in the molecular layer of the dentate gyrus (P < 0.01); higher in diestrus females than in males in the basolateral amygdala (P < 0.05); higher in diestrus females than in estrus females in the central (P < 0.01), posterodorsal medial (P < 0.01) and basolateral amygdala (P < 0.01) and higher in estrus females than in diestrus females in the strata oriens (P < 0.05) and radiatum-lacunosum-moleculare (P < 0.05) of CA1-CA3 and in the molecular layer (P < 0.05) and the hilus of the dentate gyrus (P < 0.05). The findings suggest that estrogenic regulation of the amygdala and hippocampus through GPER may be different in males and in females and may fluctuate during the estrous cycle.

Effect on Adipose Tissue of Diabetic Mice Supplemented with n-3 Fatty Acids Extracted from Microalgae.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is considered a chronic noncommunicable disease in which oxidative stress is expected as a result of hyperglycaemia. One of the most recent approaches is the study of microalgae fatty acids and their possible antioxidant effect. OBJECTIVE: This study aimed to analyse the effect of supplementation with n-3 fatty acids extracted from microalgae on the total antioxidant capacity (TAC) and lipid peroxidation of adipose tissue and plasma from diabetic (db/db) and healthy (CD1) mice. METHODS: Mice were supplemented with lyophilized n-3 fatty acids extracted from microalgae or added to the diet, from week 8 to 16. TAC assay and Thiobarbituric Acid Reactive Substances assay (TBARS) were performed on adipose tissue and plasma samples. RESULTS: The supplementation of lyophilized n-3 fatty acids from microalgae increased the total antioxidant capacity in adipose tissue of diabetic mice (615.67µM Trolox equivalents vs 405.02µM Trolox equivalents from control mice, p<0.01) and in the plasma of healthy mice (1132.97±85.75µM Trolox equivalents vs 930.64±32µM Trolox equivalents from modified diet mice, p<0.01). There was no significant effect on lipid peroxidation on both strains. CONCLUSION: The use of n-3 fatty acids extracted from microalgae could be a useful strategy to improve total antioxidant capacity in T2DM.

Blocking of Estradiol Receptors ERα, ERß and GPER During Development, Differentially Alters Energy Metabolism in Male and Female Rats.

Estradiol not only participates in the regulation of energy metabolism in adulthood, but also during the first stages of life as it modulates the alterations induced by under- and over-nutrition. The objectives of the present study were to determine: 1) If estradiol is involved in the normal programming of energy metabolism in rats; 2) If there is a specific window of time for this programming and 3) If males and females are differentially vulnerable to the action of this hormone. Estrogen receptors (ER) α, ERß and GPER were blocked by their specific antagonists MPP, PHTPP and G15, respectively, from postnatal day (P) 1 (the day of birth) to P5 or from P5 to P13. Physiological parameters such as body weight, fat depots and caloric intake were then analysed at P90. Hypothalamic AgRP, POMC, MC4R, ERα, ERß and GPER mRNA levels and plasma levels of estradiol, were also studied. We found that blocking ER receptors from P5 to P13 significantly decreases long-term body weight in males and hypothalamic POMC mRNA levels in females. The blocking of ERs from P1 to P5 only affected plasma estradiol levels in females. The present results indicate programming actions of estradiol from P5 to P13 on body weight in male and POMC expression in female rats and emphasize the importance of including both sexes in metabolic studies. It is necessary to unravel the mechanisms that underlie the actions of estradiol on food intake, both during development and in adulthood, and to determine how this programming differentially takes place in males and females.

Dietary patterns, central obesity and serum lipids concentration in Mexican adults.

INTRODUCTION: Introduction: dietary patterns (DP) analyse the relationship between consumption of foods or nutrients and disease or health outcomes. High prevalence of obesity in adults in Mexico is associated with factors such as high consumption of certain food groups and nutrients. However, few studies have been conducted to explore associations between dietary patterns and obesity in apparently healthy adults. Objective: to identify major dietary patterns (DP) associated with central-obesity (CO) and lipid concentrations in healthy adults. Methods: longitudinal study including usual dietary intakes derived from multiple 24-hour-recalls. Waist-circumference (WC) and biochemical measurements were obtained by standardized procedures and DP by principal component analysis. Adjusted-logistic regression was used to examine associations between DP, CO and serum-lipid concentrations. Results: three DP were identified: healthy-DP, risky-DP and empty-DP. Participants in the healthy-DP were more likely to have lower risk for central-obesity according to WC criteria (OR = 0.31, CI = 0.12, 0.82), p = 0.017, but also had the highest risk for elevated LDL-cholesterol (OR = 2.98, CI = 1.16, 7.66), p = 0.030. There was no significant association between risky and empty DP with obesity or overweight by body mass index (BMI), central-obesity by WC or serum lipid abnormalities. Conclusions: the healthy-DP is associated with lower risk for CO, with higher risk for elevated LDL-cholesterol. It is necessary to develop longitudinal studies of foods and nutritional analysis of the diet to clarify these associations, to promote the reduction of modifiable risk factors.

INTRODUCCIÓN: Introducción: los patrones de dieta (PD) analizan la relación entre el consumo de alimentos o nutrimentos con la salud y el desarrollo de enfermedades en poblaciones. La elevada prevalencia de obesidad en adultos mexicanos se asocia con factores como el elevado consumo de ciertos grupos de alimentos y nutrimentos. Sin embargo, pocos estudios han explorado la asociación entre los patrones dietéticos y la obesidad en adultos aparentemente sanos. Objetivo: identificar los patrones dietéticos (PD) asociados con la obesidad central (OC) y las concentraciones séricas de lípidos en adultos. Métodos: estudio longitudinal del consumo dietético obtenido de múltiples recordatorios de consumo de 24 horas. La circunferencia de cintura (CC) y las mediciones bioquímicas se obtuvieron mediante procedimientos estandarizados; los PD, por análisis del componente principal. Mediante regresión logística se identificaron las asociaciones entre PD, OC y las concentraciones séricas de lípidos. Resultados: se identificaron tres PD: PD saludable, PD de riesgo y PD vacío. Los participantes del PD saludable presentaron menor riesgo de OC de acuerdo con los criterios de la CC (OR = 0.31, CI = 0.12, 0.82), p = 0.017, pero también fueron los que presentaron mayor riesgo de cifras elevadas de colesterol-LDL (OR = 2.98. CI = 1.16, 7.66), p = 0.030. No hubo asociación estadísticamente significativa entre el PD de riesgo y el PD vacío con obesidad o sobrepeso por IMC, OC por CC o con la presencia de dislipidemias. Conclusiones: el PD saludable se asocia con un menor riesgo para OC pero con mayor riesgo de elevación del colesterol-LDL. Se necesitan estudios longitudinales para esclarecer estas asociaciones para promover la reducción de factores de riesgo modificables.