Dietary flavonoid kaempferol reduces obesity-associated hypothalamic microglia activation and promotes body weight loss in mice with obesity.

BACKGROUND: Obesity results from an unbalance in the ingested and burned calories. Energy balance (EB) is critically regulated by the hypothalamic arcuate nucleus (ARC) by promoting appetite or anorectic actions. Hypothalamic inflammation, driven by high activation of the microglia, has been reported as a key mechanism involved in the development of diet-induced obesity. Kaempferol (KF), a flavonoid-type polyphenol present in a large number of fruits and vegetables, was shown to regulate both energy metabolism and inflammation. OBJECTIVES: In this work, we studied the effects of both the central and peripheral treatment with KF on hypothalamic inflammation and EB regulation in mice with obesity. METHODS: Obese adult mice were chronically (40 days) treated with KF (0.5 mg/kg/day, intraperitoneally). During the treatment, body weight, food intake (FI), feed efficiency (FE), glucose tolerance, and insulin sensitivity were determined. Analysis of microglia activation in the ARC of the hypothalamus at the end of the treatment was also performed. Body weight, FI, and FE changes were also evaluated in response to 5µg KF, centrally administrated. RESULTS: Chronic administration of KF decreased ∼43% of the density, and ∼30% of the ratio, of activated microglia in the arcuate nucleus. These changes were accompanied by body weight loss, decreased FE, reduced fasting blood glucose, and a tendency to improve insulin sensitivity. Finally, acute central administration of KF reproduced the effects on EB triggered by peripheral administration. CONCLUSION: These findings suggest that KF might fight obesity by regulating central processes related to EB regulation and hypothalamic inflammation.

Effects of the Treatment with Flavonoids on Metabolic Syndrome Components in Humans: A Systematic Review Focusing on Mechanisms of Action.

Diets high in bioactive compounds, such as polyphenols, have been used to mitigate metabolic syndrome (MetS). Polyphenols are a large group of naturally occurring bioactive compounds, classified into two main classes: non-flavonoids and flavonoids. Flavonoids are distributed in foods, such as fruits, vegetables, tea, red wine, and cocoa. Studies have already demonstrated the benefits of flavonoids on the cardiovascular and nervous systems, as well as cancer cells. The present review summarizes the results of clinical studies that evaluated the effects of flavonoids on the components of the MetS and associated complications when offered as supplements over the long term. The results show that flavonoids can significantly modulate several metabolic parameters, such as lipid profile, blood pressure, and blood glucose. Only theaflavin and catechin were unable to affect metabolic parameters. Moreover, only body weight and body mass index were unaltered. Thus, the evidence presented in this systematic review offers bases in support of a flavonoid supplementation, held for at least 3 weeks, as a strategy to improve several metabolic parameters and, consequently, reduce the risk of diseases associated with MetS. This fact becomes stronger due to the rare side effects reported with flavonoids.

How intrauterine growth restriction due to nutritional stress changes the function of key proteins in brain serotonin metabolism during development.

This review aimed to describe and comment on how experimental intrauterine nutritional stress in animals produced some changes in tryptophan-5-hydroxylases (TPH) 1 and 2 in the brain and other key proteins such as plasma albumin, and how the intrauterine nutritional stress could produce long-lasting alterations in serotonin function in the brain of human infants.

El objetivo de esta revisión es describir y comentar cómo el estrés nutricional intrauterino experimental en animales produjo algunos cambios en las triptófano-5-hidroxilasas 1 y 2 en el cerebro y en otras proteínas clave, como la albúmina plasmática, y de qué manera el estrés nutricional intrauterino podría producir alteraciones duraderas en la función de la serotonina en el cerebro de lactantes.

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.

Caracterización de células serotoninérgicas en el tejido cardiaco fetal / Characterization of serotonergic cells in fetal heart tissue

Objetivo: Caracterizar morfológica y bioquímicamente células productoras de serotonina durante el desarrollo del tejido cardiaco. Material y métodos: Se utilizaron ratas gestantes de la cepa Wistar. A los días 10, 12, 16 y 20 de gestación se obtuvieron los fetos por cesárea, a los cuales se les disecaron los corazones, que se fijaron para los ensayos de inmunohistoquímica para triptófano- 5-hidroxilasa (Tph), además se efectuó Western Blot para la enzima; se determinó la concentración de serotonina y la actividad de Tph por cromatografía de líquidos de alta resolución. Los resultados fueron analizados mediante U de Mann-Whitney, aceptando un nivel de significación de p < 0.05. Resultados: En los cortes de corazón fetal, desde el día 10 de gestación se observaron células inmunorreactivas para Tph, con metacromasia en su interior. Fibras nerviosas inmunorreactivas para la misma enzima que hacen contacto probablemente con las células serotoninérgicas. La actividad enzimática y la concentración de la serotonina aumentaron con la edad gestacional, además, se encontró la proteína enzimática por Western- Blot en el corazón fetal de 16 días de gestación. Conclusiones: Se demostró la presencia de células productoras de serotonina en el miocardio fetal, cuyo fenotipo corresponde a mastocitos cardiacos, lo cual sugiere que la serotonina puede ser importante en el desarrollo del tejido cardiaco y que también participa en los mecanismos fisiopatológicos de los defectos cardiacos estructurales o en la predisposición a enfermedades cardiovasculares en el adulto.

BACKGROUND: We undertook this study to present biochemical and morphological characterization of serotonergic cells during fetal heart development. METHODS: Wistar rats (10, 12, 16 and 20 days of gestation) were used. After obtaining the fetuses by Cesarean section, the hearts were removed and fixed for immunohistochemical assay of tryptophan-5-hydroxylase (Tph), in addition to Western blot for enzyme. Serotonin concentration and Tph were also evaluated with high-performance liquid chromatography. Results were analyzed using Mann-Whitney U test with a significance level of p <0.05. RESULTS: Metachromatic cells immunoreactive for Tph were observed from day 10 of gestation. Nerve fibers were also labeled, apparently making contact with serotonergic cells. Tph activity was measurable and serotonin levels increased with gestational age. The presence of Tph protein was confirmed by Western blot on day 16. CONCLUSIONS: The present results support the existence of cells located in the fetal myocardium, capable of producing serotonin whose phenotype belongs to cardiac mast cells. Their presence in this tissue strongly suggests that serotonin may play a key role in normal and abnormal development of cardiac tissue.

Effects of chronic solvent abuse exposure on umami taste perception.

Inhalant abuse constitutes an important public health problem in Mexico that is more prevalent among children and adolescents. Commercial products that are abused are complex mixtures of solvents containing mainly toluene, in association with other solvents like benzene and xylene. Epidemiological evidence indicates that chronic solvent abuse exposure can cause loss of appetite among other unwanted effects. The mechanisms by which loss of appetite is produced are unknown. It is a matter of interest to determine if loss of appetite is related to changes in taste perception. One of the basic flavors detected by the taste system is umami taste (monosodium glutamate) and it has been proposed that glutamatergic receptors can play an important role in umami taste transduction and perception. It is unknown however, if chronic solvent abuse exposure can induce alterations in umami taste perception. The purpose of this work was to determine if chronic solvent exposure in rats causes alterations in glutamate solution consumption. Rats were exposed to solvents (6000 ppm) in a static chamber for 2 months, as follows: a toluene group, a benzene group, a xylene group and a control group. During the treatment, glutamate solution (120 mM) consumption, food intake and rat weights were measured. The results show that glutamate solution intake was increased in rats chronically exposed to solvents, with differences in consumption patterns between solvents. In addition, chronically exposed animals had a lower weight increase compared with unexposed rats. These data suggest that solvent inhalation originates feeding behavior alteration in rats.

Characterization of serotonergic cells in fetal heart tissue.

BACKGROUND: We undertook this study to present biochemical and morphological characterization of serotonergic cells during fetal heart development. METHODS: Wistar rats (10, 12, 16 and 20 days of gestation) were used. After obtaining the fetuses by Cesarean section, the hearts were removed and fixed for immunohistochemical assay of tryptophan-5-hydroxylase (Tph), in addition to Western blot for enzyme. Serotonin concentration and Tph were also evaluated with high-performance liquid chromatography. Results were analyzed using Mann-Whitney U test with a significance level of p <0.05. RESULTS: Metachromatic cells immunoreactive for Tph were observed from day 10 of gestation. Nerve fibers were also labeled, apparently making contact with serotonergic cells. Tph activity was measurable and serotonin levels increased with gestational age. The presence of Tph protein was confirmed by Western blot on day 16. CONCLUSIONS: The present results support the existence of cells located in the fetal myocardium, capable of producing serotonin whose phenotype belongs to cardiac mast cells. Their presence in this tissue strongly suggests that serotonin may play a key role in normal and abnormal development of cardiac tissue.

Expression of tryptophan hydroxylase in developing mouse taste papillae.

Gustatory papillae and associated taste buds receive and process chemical information from the environment. In mammals, their development takes place during the late phase of embryogenesis. However, the cellular factors that regulate the differentiation of taste papillae remain largely unknown. Here, we show by quantitative real time RT-PCR that both isoforms of tryptophan hydroxylase (TPH1 and TPH2), the first and rate limiting enzyme of serotonin (5-HT) synthesis, are expressed in developing circumvallate papillae. Immuno-staining experiments further indicated that TPH is localized both in gustatory fibers and in differentiated taste receptor cells. These results point to the synthesis of 5-HT in gustatory papillae, and allow one to hypothesize that the development of taste buds might be modulated by serotonin.