Maternal obesity and late effects on offspring metabolism / Obesidade materna e efeitos tardios sobre o metabolismo da prole

Objective : The aim of this study was to evaluate the late effects of maternal obesity induced by lesion of the ventromedial hypothalamus on offspring metabolism.Materials and methods : Thirty days after the bilateral lesion of the ventromedial hypothalamus, female rats were mated and divided into 2 groups of pregnant animals: Control (C) – false lesion (sham) and Obese (OB) – lesion. Three months after that, with the groups of mothers, offspring were divided into control and obese animals that received a normocaloric diet (C-N and OB-N), and control and obese animals that received a hypercaloric diet (C-H and OB-H). At 120 days of age, the animals were euthanized and their carcasses, feces and food were submitted to calorimetric analysis to determine energy balance and body composition.Results : During the growth period, offspring from obese mothers showed higher values of body weight and food intake than controls. Obese animals showed higher body weight gain and gross food efficiency than control animals in adulthood. The hypercaloric diet led to increased metabolizable energy intake, percentage of absorbed energy and energy expenditure in both groups. Body composition was only affected by the association of hypercaloric diet and maternal obesity that led to increased body fat.Conclusions : Maternal obesity has led to the development of later overweight in offspring, suggesting fetal programming. According to the trend presented, it is believed that the prolonged intake of hypercaloric diets in adult animals may, as an additional effect, induce worsening of the overweight induced by maternal obesity. Arq Bras Endocrinol Metab. 2014;58(3):301-7.

Objetivo Avaliar os efeitos tardios da obesidade materna induzida por lesão do núcleo ventromedial do hipotálamo sobre o metabolismo da prole. Trinta dias após a lesão bilateral do hipotálamo ventromedial, ratos fêmeas foram colocadas para acasalar e divididas em dois grupos de animais gestantes: Controle (C) – falsa lesão e Obeso (OB) – lesionados. Três meses após o nascimento, de acordo com os grupos das mães, os filhotes foram divididos em animais controle e obesos que recebiam dieta normocalórica (C-N and OB-N) e animais controle e obesos que recebiam dieta hipercalórica (C-H and OB-H). Aos 120 dias de idade, os animais foram eutanasiados e as carcaças, fezes e ração foram submetidas à análise calorimétrica para determinação do balanço energético e composição corporal.Resultados Durante o período de crescimento, os filhos de mães obesas mostraram maiores valores de peso corporal e ingestão alimentar que animais controle. Os animais obesos apresentaram maiores valores de ganho de peso corporal e eficiência metabólica que os animais controle quando adultos. A dieta hipercalórica levou ao aumento da energia metabolizável, percentagem de energia absorvida e gasto energético para ambos os grupos. A composição corporal foi somente afetada pela associação da dieta hipercalórica com a obesidade materna que levou ao aumento da gordura corporal.Conclusões : A obesidade materna levou ao sobrepeso tardio na prole, sugerindo uma programação fetal. Pela tendência apresentada, acreditamos que a ingestão prolongada de dietas hipercalóricas em animais adultos possa induzir uma piora no quadro de sobrepeso induzido pela obesidade materna. Arq Bras Endocrinol Metab. 2014;58(3):301-7.

Experimental model to induce obesity in rats

The etiology of obesity is multifactorial and is becoming a problem of public health, due to its increased prevalence and the consequent repercussion of its comorbidities on the health of the population. The great similarity and homology between the genomes of rodents and humans make these animal models a major tool to study conditions affecting humans, which can be simulated in rats. Obesity can be induced in animals by neuroendocrine, dietary or genetic changes. The most widely used models to induce obesity in rats are a lesion of the ventromedial hypothalamic nucleus (VMH) by administering monosodium glutamate or a direct electrical lesion, ovariectomy, feeding on hypercaloric diets and genetic manipulation for obesity.

A obesidade tem etiologia multifatorial e está se tornando um problema de saúde pública devido ao aumento da sua prevalência e a conseqüente repercusão das suas comorbidades na saúde da população. A grande similaridade e homologia entre os genomas dos roedores e dos humanos tornam esses modelos animais uma importante ferramenta para o estudo de condições que afetam os humanos e que podem ser simuladas em ratos. A obesidade pode ser induzida em animais com alterações neuroendócrinas, dietéticas ou genéticas. Os modelos mais utilizados para indução de obesidade em ratos são lesão do núcleo hipotalâmico venteromedial (VMH) através da administração de glutamato monossódico ou lesão elétrica direta, ooforectomia, alimentação com dietas hipercalóricas e manipulação genética para obesidade.

Postnatal Development of Brain Natriuretic Peptide-immunoreactive Neuron in the Hypothalamus of the Rat / 체질인류학회지

Brain natriuretic peptide (BNP) is a neuropeptide, isolated from porcine brain that is homologous with atriopeptin. Magnocellular neurosecretory cells located in the paraventricular nucleus and supraoptic nucleus synthesize and secrete neurohormones. The purpose of this study was to investigate distribution of BNP immunoreactivity throughout the rat hypothalamus from the day of birth to 30 days and adult using immunoperoxidase and immunofluorescent staining. The first BNP immunoreactive neurons appeared in the paraventricular and supraoptic nucleus at P10. In adult, BNP immunoreactivity was widely distributed throughout regions of the hypothalamus including dorsomedial hypothalamic nucleus, ventromedial hypothalamic nucleus, arcuate nucleus and internal layer of median eminence. The intensity of BNP immunoreactivity was weak in almost all hypothalamic nuclei except the paraventricular and supraoptic nuclei. BNP immunoreactivity was first observed in the lateral hypothalamic area at P15. In retrochiasmatic supraoptic nucleus, BNP immunoreactivity was first observed at P20 and remarkably distributed in adult. In the present study, distinct localization of BNP immunoreactivity was in the hypothalamic cell bodies and fibers. Although the role of BNP in the brain is yet to be determined, these results indicate that BNP in the neurons of hypothalamus play important role in the regulation of a variety of neurosecretory functions as a neuromodulator during postnatal development of the hypothalamus.

Postnatal Development of Brain Natriuretic Peptide-immunoreactive Neuron in the Hypothalamus of the Rat / 체질인류학회지

Brain natriuretic peptide (BNP) is a neuropeptide, isolated from porcine brain that is homologous with atriopeptin. Magnocellular neurosecretory cells located in the paraventricular nucleus and supraoptic nucleus synthesize and secrete neurohormones. The purpose of this study was to investigate distribution of BNP immunoreactivity throughout the rat hypothalamus from the day of birth to 30 days and adult using immunoperoxidase and immunofluorescent staining. The first BNP immunoreactive neurons appeared in the paraventricular and supraoptic nucleus at P10. In adult, BNP immunoreactivity was widely distributed throughout regions of the hypothalamus including dorsomedial hypothalamic nucleus, ventromedial hypothalamic nucleus, arcuate nucleus and internal layer of median eminence. The intensity of BNP immunoreactivity was weak in almost all hypothalamic nuclei except the paraventricular and supraoptic nuclei. BNP immunoreactivity was first observed in the lateral hypothalamic area at P15. In retrochiasmatic supraoptic nucleus, BNP immunoreactivity was first observed at P20 and remarkably distributed in adult. In the present study, distinct localization of BNP immunoreactivity was in the hypothalamic cell bodies and fibers. Although the role of BNP in the brain is yet to be determined, these results indicate that BNP in the neurons of hypothalamus play important role in the regulation of a variety of neurosecretory functions as a neuromodulator during postnatal development of the hypothalamus.

Hypothalamo-limbic involvement in modulation of tooth-pump stimulation evoked nociceptive response in rats.

The hypothalamo-limbic system has been implicated in recognizing the affective significance of pain and elicitation of related emotional responses. Several evidences from different studies support a role of these areas in endogenous analgesic mechanisms for pain modulation as elucidated by different pain tests in more than one animal model. In the above context, the aim of this study was to investigate the relative effectiveness of the pain modulatory action of hypothalamic and limbic structures in rat using similar stimulation parameters, and studying the effect on tooth pulp stimulation evoked jaw opening reflex (TP-JOR). To achieve the objective, unilateral stimulation of hypothalamic (lateral = LH; ventromedial = VMN; anterior = AH) and limbic areas (amygdala = AMYG; hippocampus = HIPP) was done on the TP-JOR test. A significant reduction in the amplitude of EMG recorded from the digastric muscle (dEMG) as a result of tooth-pulp stimulation was observed on stimulation of LH, VMN, AMYG and HIPP but not from AH. Also, the magnitude of this effect was almost similar from these areas. The results suggest that these areas (except AH) have an antinociceptive role in tooth-pulp stimulation evoked pain response.

Location of CNS Labeled Neurons Innervating the Rat Thymus Using the Pseudorabies Virus / 체질인류학회지

This experimental studies was to investigate the location of CNS labeled neurons following injection of pseudorabies virus (PRV), Bartha strain, into the rat thymus. After survival times of 96~120 hours following injection of PRV, the rats were perfused, and their spinal cord and brain were frozen sectioned(30micrometer). These sections were stained by PRV immunohistochemical staining method, and observed with light microscope The results were as follows: 1. The PRV labeled spinal cord segments projecting to the rat thymus were founded in cervical and thoracic segments. Densely labeled areas of each spinal cord segment were founded in lamina V, VII, X, intermediolateral nucleus and dorsal nucleus. 2. In the rhombencephalon, PRV labeled neurons projecting to the thymus were founded in the A1 noradrenalin cells/C1 adrenalin cells/caudoventrolateral reticular nucleus, rostroventro-lateral reticular nucleus, medullary reticular nucleus, area postrema, nucleus solitary tract, nucleus raphe obscurus, nucleus raphe pallidus, nucleus raphe magnus, gigantocellular reticular nucleus, lateral paragigantocellular nucleus and spinal trigeminal nucleus. 3. In the mesencephalon, PRV labeled neurons were founded in parabrachial nucleus, Kolliker-Fuse nucleus, central gray matter, substantia nigra, nucleus dorsal raphe, A8 dopamin cells of retrorubral field, Edinger-Westphal nucleus, locus coeruleus, subcoeruleus nucleus and A5 noradrenalin cells. 4. In the prosencephalon, PRV labeled neurons were founded in reuniens thalamic nucleus, paraventricular thalamic nucleus, precommissural nucleus, paraventricular hypothalamic nucleus, anterior hypothalamic nucleus, lateral hypothalamic nucleus, preoptic hypothalamic nucleus, retrochiasmatic area, arcuate nucleus, dorsomedial hypothalamic nucleus and ventromedial hypothalamic nucleus. These results suggest that PRV labeled neurons of the spinal cord projecting to the rat thymus might be the neurons related to the viscero-somatic sensory and sympathetic preganglionic neurons, and PRV labeled neurons of the brain may be the neurons response to the movement of smooth muscle in blood vessels. These PRV labeled neurons may be central autonomic center related to the integration and modulation of reflex control linked to the sensory system monitoring the internal environment. These observations provide evidence for previously unknown projections from spinal cord and brain to the thymus which may be play an important role in the regulation of thymic function.

Ventromedial hypothalamic nuclei and feding behavior

The role of the ventromedial nuclei of the hypothalamus [VMN] in food behavior was studied in adult male rats, allocated in 3 groups: control, sham and lesioned. Electrolytic lesions were induced stereotaxically [1.2 mA, 15 sec]. Results revealed a significant decrease [p<0.05] in body weight [BW] and food intake [FI] in the order of lesioned

Regional specificity seen within hypothalamus in neuroimmunomodulation.

Wistar strain male albino rats lesioned and sham lesioned at Ventromedial hypothalamus (VMH) were used to study the neuroimmunomodulation by this brain region. Except the decrease in thymus weight/body weight ratio (P < 0.01), and its cellularity (P < 0.02) in immunized VMH lesion animals, the rest of the parameters like plaque forming cells (PFC), antibody titre, leukocyte migration inhibition index, foot pad thickness in the lesioned as well as the lesion immunized animals never deviated from their respective sham and immunized sham animals. Sham operated belongs to VMH when compared to control rats, showed marked decrease in spleen weight (P < 0.001), thymus weight (P < 0.02) and decrease in popliteal lymph node weight (P < 0.001) ratios. After immunization, the immunized sham animals showed a marked decrease in antibody titre (P < 0.05), PFC (P < 0.05), spleen (P < 0.05) and thymus (P < 0.001) weight ratios with the significant increase in splenic cell count (P < 0.01) compared to immunized control rats. VMH may be one of the information receiving center. However, from these results, it is inferred that VMH could not be a modulating center for the many of the parameters studied as far as neuroimmunomodulation is concerned.

Anorexigenic effect of fecal extract from ventromedial hypothalamic (VMH) lesioned rats on normal rats.

Feces of ventromedial hypothalamus (VMH) lesioned obese and sham operated (SL) rats were separately pooled and subjected to column chromatography using sephadex G-150. Fractions showing peak absorption at 280 nm, obtained from respective group of rats were separately pooled and divided into 9 equal aliquots and injected ip in two groups of overnight fasted normal rats (OFN rats). Rats injected with fecal extract from VMH lesioned rats showed decreased food and water intake which was not seen in rats treated with the fecal extract from SL rats suggesting the possible presence of an anorexigenic substance in the feces of VMH lesioned rats but absent in SL rats.

Possible action of intracerebroventricular thyrotropin on Brobeck's hypothesis.

The effect of ICV administered TSH on Brobeck's thermostatic hypothesis was evaluated by recording chronological changes in electrical activity of precise loci (POA, VMN and CO) coupled by rectal temperature changes in dogs. The study revealed 1. TSH action on thermoregulation is biphasic in nature. 2. This action of TSH is not an independent act but depends on the reaction of satiety centre.

Effects of central administration of insulin in normal and VMH (ventromedial hypothalamus) lesioned rats on food intake.

Central effects of insulin on 20 min. food intake were studied in rats. Insulin administration in the lateral ventricular cerebrospinal fluid (CSF) did not alter food intake in the intact or lesioned ventromedial hypothalamus (VMH) rats. Whereas, after insulin injection in VMH there was a decrease in food intake. In VMH lesioned rats, subcutaneous injection of insulin increased food intake.

Relación entre las lesiones electrolíticas del núcleo hipotalámico ventromedial y la diabetes mellitus insulino dependiente inducida por streptozotocina

Dada la función reguladora del sistema nervioso sobre el endocrino se busca analizar la correlación entre la lesión del núcleo hipotalámico ventromedial (HVM) y la severidad de la diabetes inducida por estreptozotocina (STZ). Se utilizan 29 ratas divididas en cuatro grupos: Grupo I: lesión del HVM e inyección de SS (murieron por complicaciones respiratorias); Grupo III: lesión del HVM e inyección de STZ; Grupo IV: lesión ficticia del HVM e inyección de STZ. Se observan por un período de 6 a 8 semanas. Se exploran semanalmente valores de química sanguínea como glicemia, colesterol y triglicéridos y se mide el peso corporal; cada dos días se determina el consumo de agua y en el momento del sacrificio se pesa la grasa perirrenal y se fijan los cerebros para determinar tamaño y sitio de la lesión. Los resultados muestran que el grupo III es el más afectado en cuanto a severidad de la diabetes y velocidad de deterioro de los animales; mientras que el grupo I sólo muestra aumento de peso corporal pero sin evidencia de diabetes. Todo parece indicar que el aumento de la ingesta inducido por la lesión del "núcleo de la sacidad" y por la misma diabetes produce efectos aditivos sobre el cuadro patológico

Morphological alterations of the rat submandibular gland caused by lesion of the ventromedial nucleus of the hypothalamus

As características morfológicas da glândula submandibular de ratos foram estudadas em diferentes períodos de tempo (5, 10, 20, 40 e 90 dias) após a lesäo do núcleo ventromedial do hipotálamo. O arranjo estrutural da glândula submandibular foi o mesmo em ratos com lesäo do núcleo ventromedial e nos ratos controle ou com lesäo fictícia. No primeiro grupo, entretanto, o septo estava estreito, dificultando a definiçäo dos compartimentos lobulares. Alteraçöes do parênquima foram bastante evidentes nos ratos lesados, com hipotrofia acinar e aumento no número de ductos granulosos. Os componentes submandibulares restantes, entretanto, näo apresentaram alteraçöes quando comparados com aqueles dos animais controles. Em resumo, a lesäo do núcleo ventromedial do hipotálamo produz as seguintes mudanças na glândula submandibular do rato: 1) diminuiçäo da massa glandular; 2) hipotrofia acinar; e 3) aumento no número de ductos granulosos

Efectos de la extirpación estereotaxica del nucleo amigdalino basolateral sobre la ultraestructura del nucleo hipotalámico ventromedial

Hemos empleado 40 ratas macho, cepa Wistar, de 2 meses de edad. Los animales se dividieron en 20 ratas controles (10 ratas intactas y 10 ratas sometidas a operación simulada), y 20 animales experimentales (10 sacrificados al mes y 10 sacrificados a los dos meses de la operación quirúrgica). El método experimental fue la extirpación extereotáxica del nucleo amigdalino basolateral de la amígala cerebral. Hemos estudiado la ultraestructura del nucleo ventromedial del hipotálamo. Hemos observado un incremento de la actividad de las neuronas del nucleo hipotalámico ventromedial en los animales experimentales (aumento del retículo endodplasmático rugoso, del aparato de Golgi, de los cuerpos densos, y de las mitocondrias con matriz densa), y en las sinapsis (un incremento de las vesículas y de los gránulos densos). Nuestros resultados demuestran que el nucleo amigdalino basolateral ejerce un efecto inhibidor de la actividad neuronal del nucleo hipotalámico ventromedial

Lesión de los núcleos hipotalámicos ventromediales y secreción de insulina: correlaciones clínicas y experimentales / Ventromedial lesions and hypothalamically induced insulin release: clinical and experimental correlations

Los NHVM son un área de integración y comando de la liberación de GRF, de la sensación de saciedad y del tono simpático. Su lesión se traduce en una caída de GRF (y GH), predominando las AHL (parasimpático), con hiperinsulinismo, hiperfagia, lipogénesis acelerada, glicemia normal, lo que lleva a la constitución de un síndrome de obesidad hipotalámica. El crecimiento puede no ser afectado durante lapsos variables, aparentemente como consecuencia de la hiperinsulinemia