Leticia Manuel-Apolinar

Fetal Malnutrition Affects Hypothalamic Leptin Receptor Expression After Birth in Male Mice

BACKGROUND AND AIMS Epidemiological associations between an adverse intrauterine environment and the induction of obesity in adult life led to the concept of fetal programming whereby an unfavorable prenatal environment induces adaptations that improve fetal survival or prepare the fetus in expectation of a particular range of postnatal environments. However, these adaptations (predictive adaptive responses) may later prove to be a disadvantage when the pre- and postnatal environments show discrepancies. We investigated the effect of maternal restricted diet on body weight and expression of hypothalamic Ob-Rb of the offspring. METHODS Balb C mice were mated after pregnancy and were randomly assigned to control (C) and undernutrition group (UN) groups. Control group was allowed food ad libitum and UN group had a 50% restriction of food intake during gestation. In the present study we assessed changes in hypothalamic Ob-Rb mRNA by RT-PCR in offspring from C and UN groups. RESULTS The offspring of UN at birth showed 17% less body weight compared with C, but at 90 days the UN had a greater body weight than C (p<0.01). The UN group also presented an increase in the expression of Ob-Rb at 90 postnatal days (p<0.01). CONCLUSIONS The results suggest that maternal caloric restriction programs a greater expression of Ob-Rb in the hypothalamus in offspring, as well as a body weight gain that persists into adulthood. In addition, changes in Ob-Rb expression suggest that Ob-Rb mRNA in the hypothalamus is sensitive to fetal undernutrition.

Role of prenatal undernutrition in the expression of serotonin, dopamine and leptin receptors in adult mice: Implications of food intake

Perturbations in the levels of serotonin expression have a significant impact on behavior and have been implicated in the pathogenesis of several neuropsychiatric disorders including anxiety, mood and appetite. Fetal programming is a risk factor for the development of metabolic diseases during adulthood. Moreover, previous studies have shown that serotonin (5-HT), dopamine and leptin are important in energy balance. In the present study, the impact of maternal malnutrition-induced prenatal undernutrition (UN) was investigated in mice and the expression of 5-HT1A, dopamine (D)1, D2 and Ob-Rb receptors was analyzed in the hypothalamus during adulthood. The UN group showed a low birth weight compared with the control group. With regard to receptor expression, 5-HT1A in the UN group was increased in the hypothalamus and D1 was reduced, whereas D2 showed an increase from postnatal day (P)14 in the arcuate nucleus. Ob-Rb receptor expression was increased in the hypothalamus at P14 and P90. These observations indicated that maternal caloric restriction programs a postnatal body weight gain in offspring with an increased food intake in early postnatal life which continues into adulthood. In addition, UN in mice was found to be affected by Ob-Rb, 5-HT1A and D1/2 receptor expression, indicating that these observations may be associated with hyperphagia and obesity.

Intranasal Anti-rabies DNA Immunization Promotes a Th1-related Cytokine Stimulation Associated with Plasmid Survival Time

BACKGROUND AND AIMS DNA vaccination has a great potential to decrease infectious diseases worldwide, such as rabies. Here we showed the effects of a single anti-rabies DNA vaccination applied intranasally (IN) on plasmid survival time, neutralizing antibody (NA) titers, G-protein expression and Th1/Th2-related cytokines. METHODS Only one 50-μg dose of an anti-rabies DNA vaccine was IN administered to 160 Balb/c mice. Twenty mice were used for the neutralizing antibody study, 35 for the proliferation assay, 35 for Th1/Th2-related cytokines, 35 for glycoprotein expression by immunocytochemistry, and 35 for pGQH detection and G-protein mRNA expression. RESULTS Th1-type related cytokines from spleen cells (IFN-γ, TNF-α, and IL-2) were detected. Rabies NA titers were ≥0.6 IUs from day 30 onward in the IN DNA-vaccinated group. The plasmid was identified in brains and lungs from days 3-15. The mRNA transcript was amplified in brains and lungs from days 3-30, and G-protein expression was observed in spleens, brains and lungs on days 3, 8, and 15. In all cases, a gradual decrease was observed on days 30 and 45 and absent on day 60. CONCLUSIONS We found that Th1-type related cytokines (IL-2, IFN-γ, and TNF-α) were stimulated during the first month after DNA vaccination, correlating with the proliferation assays. Also, it was associated with the plasmid survival time remaining in lungs and brains prior to its degradation.

Resistin levels are not associated with obesity in central precocious puberty

Objective: To compare serum resistin concentrations between prepubertal girls with a BMI > 85th percentile and girls with precocious puberty (CPP) who have and have not undergone GnRH analog treatment. Patients and methods: This is a cross‐sectional study in girls with a BMI > 85th percentile and a median age of 8 years. We included 31 girls with CPP who did not receive treatment (CPPoT), 23 girls with CPP who were treated with leuprolide (CPPT), 22 prepubertal girls and 24 pubertal girls. Anthropometric data and the fasting plasma concentrations of lipids, glucose, insulin, and resistin were measured. Results: The z‐BMI scores were similar among the groups (p = 0.344), and body fat percentage (BF%) was similar among CPPT, CPPoT and prepubertal girls (p = 0.151). Resistin and insulin levels were lower in girls with CPP (CPPT and CPPoT) than in prepubertal and pubertal girls (median resistin level: CPPT 11.8 pg/ml vs CPPoT 11 pg/ml vs prepubertal 16 pg/ml vs pubertal 16 pg/ml, p = 0.001; median insulin level: CPPT 10.7 &mgr;UI/mL vs CPPoT 10.2 &mgr;UI/mL vs prepubertal 14.4 &mgr;UI/mL vs pubertal 32 &mgr;UI/mL p = 0.02). ANCOVA analysis, after adjustments for pubertal stage, BF% and z‐BMI, showed that CPP modifies resistin levels (F = 31.4; p = 0.0001) independently of these parameters (p < 0.05). Conclusions: In the group of girls with overweight or obesity, the resistin level was lower in girls with CPP than in prepubertal and pubertal girls. More studies are needed to understand the role of resistin in CPP patients. HIGHLIGHTSThis study is the first to determine resistin levels in patients with CPP.CPP patients have lower concentrations of resistin than prepubertal and pubertal girls with overweight or obesity without CPP.Resistin levels were not found to be related to z‐BMI, body fat percentage or CPP treatment status.

Asociación de leptina con factores cardiometabólicos en escolares y adolescentes con hiperplasia suprarrenal congénita

espanolIntroduccion: En la hiperplasia suprarrenal congenita (HSC), la obesidad, la hiperinsulinemia y los niveles de leptina se encuentran incrementados. Objetivo: Identificar la frecuencia de los factores de riesgo cardiometabolico (FRC) en ninos y adolescentes con HSC y explorar la relacion con los niveles de leptina. Metodo: Estudio transversal de 40 pacientes a quienes se realizo somatometria y evaluacion de glucosa, insulina, trigliceridos, 17-hidroxiprogesterona, leptina, colesterol HDL y LDL en ayuno. Los pacientes fueron clasificados por el numero de FRC y se analizaron los niveles de leptina con Kruskal-Wallis. Se aplico correlacion de Pearson entre la leptina, puntuacion Z del indice de masa corporal (zIMC) y porcentaje de grasa corporal. Resultados: 50 % de los pacientes presento obesidad y sobrepeso, 59 % hipertrigliceridemia, 40 % hipoalfalipoproteinemia, 27.5 % colesterol LDL alto y 22.5 % resistencia a la insulina. Hubo correlacion positiva entre leptina y porcentaje de grasa corporal (r = 0.64), el zIMC (r = 0.55) y el numero de FRC (r = 0.65). En el analisis multivariado ajustado por obesidad, los niveles de leptina se asociaron con el numero de FRC. Conclusion: La HSC tuvo alta frecuencia de FRC y al parecer la leptina se asocio con perfil cardiometabolico mas adverso en sujetos con obesidad y sobrepeso. EnglishIntroduction: In congenital adrenal hyperplasia (CAH), obesity, hyperinsulinemia and leptin levels are increased. Objective: To identify the frequency of cardiometabolic risk factors (CRF) in children and adolescents with CAH and to explore the relationship with leptin levels. Method: Cross-sectional study of 40 patients who underwent anthropometric measurements and had fasting glucose, insulin, triglycerides, 17-hidroxyprogesterone, leptin, HDL and LDL-cholesterol assessed. The patients were classified according to the number of CRFs, and leptin levels were analyzed with the Kruskal-Wallis test. Pearson’s correlation was applied between leptin, body mass index (BMI) z-score and body fat percentage. Results: Fifty percent of the patients had obesity and overweight, 59% had hypertriglyceridemia, 40%, hypoalphalipoproteinemia, 27.5%, high LDL-cholesterol and 22.5% insulin resistance. There was positive correlation between leptin and body fat percentage (r = 0.64), BMI z-score (r = 0.55) and the number of CRFs (r = 0.65). In the obesity-adjusted multivariate analysis, leptin levels were associated with the number of CRFs. Conclusion: CAH had a high frequency of CRFs and leptin appeared to be associated with a more adverse cardiometabolic profile in subjects with obesity and overweight.

RELATIONSHIP BETWEEN SERUM LEPTIN LEVELS AND WEIGHT GAIN IN GIRLS WITH CENTRAL PRECOCIOUS PUBERTY AT 1-YEAR FOLLOW-UP

OBJECTIVE Patients with central precocious puberty (CPP) may have increased serum leptin levels; however, it is not well known whether this increase differs between patients with and without obesity. Our objectives were to describe the changes in serum leptin in girls with CPP in the first 12 months after diagnosis based on body mass index (BMI) and to explore whether serum leptin level at CPP diagnosis is related to BMI z-score (BMIz) after a 1-year follow-up. METHODS A prospective cohort study was performed. We included 42 girls with idiopathic CPP in Tanner stages II and III. Anthropometric measurements were performed, and serum leptin was measured at study initiation and after 12 months. Patients were stratified according to BMI category (30 with a BMI in the <94th percentile and 12 with a BMI in the >95th percentile). Study variables were compared. Correlations among leptin, BMIz, and body fat were assessed. RESULTS Leptin increased gradually during the first year of treatment. In girls with a BMI in the <94th percentile at diagnosis, body fat percentage increased gradually during the first year of follow-up. CONCLUSION Girls with a BMI in the <94th percentile have a greater risk of weight increase. Leptin level >10.5 ng/dL at diagnosis is a risk factor for weight gain after 1 year. ABBREVIATIONS BMI = body mass index BMIz = BMI z-score CPP = central precocious puberty GnRHa = gonadotropin-releasing hormone analogue.

Artículo de revisiónAspectos genéticos y neuroendocrinos en el trastorno del espectro autistaGenetic and neuroendocrine aspects in autism spectrum disorder

The autism spectrum disorder (ASD) was described in 1943 and is defined as a developmental disorder that affects social interaction and communication. It is usually identified in early stages of development from 18 months of age. Currently, autism is considered a neurological disorder with a spectrum covering cases of different degrees, which is associated with genetic factors, not genetic and environmental. Among the genetic factors, various syndromes have been described that are associated with this disorder. Also, the neurobiology of autism has been studied at the genetic, neurophysiological, neurochemical and neuropathological levels. Neuroimaging techniques have shown multiple structural abnormalities in these patients. There have also been changes in the serotonergic, GABAergic, catecholaminergic and cholinergic systems related to this disorder. This paper presents an update of the information presented in the genetic and neuroendocrine aspects of autism spectrum disorder.

Aspectos genéticos y neuroendocrinos en el trastorno del espectro autista

The autism spectrum disorder (ASD) was described in 1943 and is defined as a developmental disorder that affects social interaction and communication. It is usually identified in early stages of development from 18 months of age. Currently, autism is considered a neurological disorder with a spectrum covering cases of different degrees, which is associated with genetic factors, not genetic and environmental. Among the genetic factors, various syndromes have been described that are associated with this disorder. Also, the neurobiology of autism has been studied at the genetic, neurophysiological, neurochemical and neuropathological levels. Neuroimaging techniques have shown multiple structural abnormalities in these patients. There have also been changes in the serotonergic, GABAergic, catecholaminergic and cholinergic systems related to this disorder. This paper presents an update of the information presented in the genetic and neuroendocrine aspects of autism spectrum disorder.