Obese fathers lead to an altered metabolism and obesity in their children in adulthood: review of experimental and human studies / Pais obesos levam a metabolismo alterado e obesidade em seus filhos na idade adulta: revisão de estudos experimentais e humanos

Abstract Objective: To discuss the recent literature on paternal obesity, focusing on the possible mechanisms of transmission of the phenotypes from the father to the children. Sources: A non-systematic review in the PubMed database found few publications in which paternal obesity was implicated in the adverse transmission of characteristics to offspring. Specific articles on epigenetics were also evaluated. As the subject is recent and still controversial, all articles were considered regardless of year of publication. Summary of findings: Studies in humans and animals have established that paternal obesity impairs their hormones, metabolism, and sperm function, which can be transmitted to their offspring. In humans, paternal obesity results in insulin resistance/type 2 diabetes and increased levels of cortisol in umbilical cord blood, which increases the risk factors for cardiovascular disease. Notably, there is an association between body fat in parents and the prevalence of obesity in their daughters. In animals, paternal obesity led to offspring alterations on glucose-insulin homeostasis, hepatic lipogenesis, hypothalamus/feeding behavior, kidney of the offspring; it also impairs the reproductive potential of male offspring with sperm oxidative stress and mitochondrial dysfunction. An explanation for these observations (human and animal) is epigenetics, considered the primary tool for the transmission of phenotypes from the father to offspring, such as DNA methylation, histone modifications, and non-coding RNA. Conclusions: Paternal obesity can induce programmed phenotypes in offspring through epigenetics. Therefore, it can be considered a public health problem, affecting the children's future life.

Resumo Objetivo: Discutir a literatura recente sobre obesidade paterna, focalizando os possíveis mecanismos de transmissão dos fenótipos do pai para os filhos. Fontes: Uma revisão não-sistemática no banco de dados PubMed encontrou poucas publicações com obesidade paterna implicada com a transmissão adversa das características à prole. Artigos específicos sobre epigenética também foram avaliados. Como o assunto é recente e ainda controverso, todos os trabalhos foram considerados independentemente do ano de publicação. Resumo dos achados: Estudos em seres humanos e animais estabeleceram que a obesidade do pai prejudica seus hormônios, metabolismo e função espermática, que pode ser transmitida à prole. Em humanos, a obesidade paterna resulta em resistência à insulina / diabetes tipo 2 e aumento do nível de cortisol no sangue do cordão umbilical, que aumenta os fatores de risco para doença cardiovascular. Notavelmente, existe associação entre a gordura corporal nos pais e a prevalência de obesidade em suas filhas. Em animais, pais obesos condicionam, na prole, a homeostase glicose-insulina, lipogênese hepática, hipotálamo / comportamento alimentar, rim, prejudicam o potencial reprodutivo da prole masculina com estresse oxidativo espermático e disfunção mitocondrial. Uma explicação para estas observações (humanos e animais) é a epigenética, considerada a ferramenta básica para a transmissão de fenótipos do pai à prole, como a metilação do DNA, modificações nas histonas, e RNA não codificante. Conclusões: A obesidade paterna pode induzir fenótipos programados na prole através da epigenética. Portanto, a obesidade paterna pode ser considerada um problema de saúde pública, afetando a vida futura das crianças.

High-intensity interval training beneficial effects in diet-induced obesity in mice: adipose tissue, liver structure, and pancreatic islets / Efectos beneficiosos del entrenamiento con intervalos de alta intensidad en la obesidad inducida por dieta en ratones: tejido adiposo: estructura del hígado e islotes pancreáticos

The study aimed to evaluate the impact of high-intensity interval training (HIIT) on adipose tissue, pancreatic islets and liver in mice fed high-fat diet. C57BL/6 male mice were fed one of two diets: standard chow (Lean group - LE) or a high-fat diet (Obese group ­ OB). After the first 12-weeks, the animals were divided into non-trained (LE-NT and OB-NT), trained groups (LE-T and OB-T), and started the exercise protocol. The HIIT protocol in the trained animals (LE-T and OB-T) compared to their counterparts (LE-NT and OB-NT) led to a reduction in size of the pancreatic islets (LE-T vs. LE-NT -40 %, OB-T vs. OB-NT -22 %) and to an increase in insulin immunodensity in pancreatic islet (LE-T vs. LE-NT +35 %, OB-T vs. OB-NT +31 %). Apart from the above results, in adipose tissue, a decrease of the diameter of adipocytes (LE-T vs. LE-NT -23 %, OB-T vs. OB-NT -12 %), a reduction in adiposity index (LE-T vs. LE-NT -49 %, OB-T vs. OB-NT -24 %) and in the liver, a decrease in the context of hepatic steatosis (LE-T vs. LE-NT -57 %, OB-T vs. OB-NT -77 %). These metabolic changes characterize a benefits performance of the HIIT protocol in swimming. HIIT is able to mitigate the bad effects caused by high-fat diet, even with continued intake of this diet in an animal model. HIIT has the advantage of requiring only a few weekly sessions with short duration in each session. These benefits are important to motivate people who nowadays live with a lack of time condition for these activities.

El objetivo fue evaluar el impacto del entrenamiento con intervalos de alta intensidad (EIAI) sobre el tejido adiposo, el hígado y los islotes pancreáticos en ratones alimentados con dieta alta en grasas. Ratones C57BL/6, machos fueron alimentados con una de dos dietas: dieta estándar (grupo magro - MA) o una dieta alta en grasas (grupo obeso - OB). Después de las primeras 12 semanas, los animales fueron divididos en dos grupos, no entrenados (MA-NE y OB-NE) y grupos entrenados (MA-E y OB-E), y comenzaron el protocolo de ejercicio. El protocolo de IEAI en los animales entrenados (MA-E y OB-E) en comparación con sus contrapartes (MA-NE y OB-NE) condujo a una reducción en el tamaño de los islotes pancreáticos (MA-E vs. MA-NE -40 %, OB-E vs. OB-NE -22 %) y al aumento de la inmunodensidad de insulina en los islotes pancreáticos (MA-E vs. MA-NE +35 %, OB-E vs. OB-NE +31 %). Además, en el tejido adiposo se detectó una disminución del diámetro de los adipocitos (MA-E vs. MA-NE -23 %, OB-E vs. OB-NE -12 %), una reducción en el índice de adiposidad (MA-E vs. MA-NE -49 %, OB-E vs. OB-NE -24 %) y en el hígado una disminución de la esteatosis (MA-E vs. MA-NE -57 %, OB-E vs. OB-NE -77 %). Estos cambios metabólicos caracterizan una actuación beneficiosa del protocolo de EIAI en la natación. El EIAI es capaz de mitigar los efectos negativos causados por la dieta alta en grasas, incluso con la ingesta continuada de esta dieta en el modelo animal. La EIAI tiene la ventaja de requir sólo unas pocas sesiones semanales con corta duración de cada sesión. Estos beneficios son importantes para motivar a la personas en las condiciones de falta de tiempo que tienen en la actualidad.

Animal models of nutritional induction of type 2 diabetes mellitus / Modelos animales de inducción nutricional para diabetes mellitus tipo 2

Type 2 diabetes mellitus (DM2) is the most common chronic metabolic disease, affecting approximately 6% of the adult population in the Western world. This condition is a major cause of cardiovascular disease, blindness, renal failure, and amputations, with increasing prevalence worldwide. The inuence of obesity on type 2 diabetes risk is determined by the degree of obesity and by body fat localization, with insulin resistance (IR) being the main link between these metabolic diseases. Experimental studies have shown that dietary factors, and particularly lipids, are strongly positively associated with body mass (BM) gain; IR; and, consequently, type 2 diabetes. Similarly, excessive consumption of energy-dense carbohydrate-rich foods can trigger the onset of type 2 diabetes. Additionally, maternal dietary inadequacies at conception and/or during the gestational period have been proposed to lead to developmental programming of excessive BM gain and metabolic disturbances in offspring, such as abnormal glucose homeostasis, reduced whole-body insulin sensitivity, impaired beta-cell insulin secretion and changes in the structure of the pancreas. Metabolic disruption is strongly associated with deleterious effects on beta-cell development and function. However, alterations in the amount and quality of dietary fat can modify glucose metabolism and insulin sensitivity. In this way, certain oils have gained attention in experimental research for their beneficial effects. Olive oil, a source of monounsaturated fatty acids (MUFAs), got attention in the past for its capacity to prevent cardiovascular diseases. Nevertheless, it is currently known that this oil also improves insulin sensitivity and glycemic control. Canola oil, flaxseed oil and especially fish oil (rich in n-3 polyunsaturated fatty acids) were first described as effective dietary nutrients against hypertriglyceridemia but now are known to have positive effects on glucose metabolism as well.

La diabetes mellitus tipo 2 (DM2) es la enfermedad metabólica crónica más común, afectando aproximadamente al 6% de la población adulta en el mundo occidental. Esta condición es una causa importante de las enfermedades cardiovasculares, la ceguera, la insuficiencia renal, y las amputaciones, con un aumento de su prevalencia en todo el mundo. El riesgo de obesidad en la diabetes tipo 2 está determinado por el grado de obesidad y localización de la grasa corporal, siendo la resistencia a la insulina (RI) la principal relación entre estas enfermedades metabólicas. Los estudios experimentales han demostrado que los factores dietéticos, y en particular los lípidos, se asocian de manera importante con la masa corporal (MC), la IR y la diabetes tipo 2. Asimismo, el consumo excesivo de alimentos ricos en carbohidratos de alto contenido energético pueden provocar la diabetes tipo 2. Además, se ha sugerido que una dieta materna inadecuada al momento de concebir o durante el período de gestación daría lugar al desarrollo de la excesiva MC y de trastornos metabólicos en los hijos, tales como la homeostasis anormal de la glucosa, reducción de la sensibilidad a la insulina en todo el cuerpo, el deterioro en la función de células beta, resistencia a la insulina y cambios en la estructura del páncreas. La alteración metabólica está asociada de forma importante con los efectos dañinos sobre el desarrollo y función de las células beta. Sin embargo, las alteraciones en la cantidad y la calidad de la grasa dietética pueden modificar el metabolismo de la glucosa como también la sensibilidad a la insulina. De esta manera, la investigación experimental ha enfocado la atención en algunos aceites debido a sus efectos beneficiosos. El aceite de oliva, es una fuente de monoinsaturados y actualmente se sabe que este aceite también mejora la sensibilidad a la insulina y el control glucémico El aceite de canola, el aceite de linaza y especialmente el aceite de pescado (rico en omega-3 los ácidos grasos poliinsaturados (PUFAs)) fueron descritos por primera vez como nutrientes de la dieta eficaces contra la hipertrigliceridemia, sin embargo, es sabido que además tienen efectos positivos sobre el metabolismo de la glucosa.

Determination of insulin-like growth factor-I reference values using an immunoradiometric assay in a Brazilian adult population.

Background: Serum levels of total insulin-like growth factor I (IGF-I) reflect endogenous growth hormone (GH) secretion in healthy adults, which makes it a good diagnostic marker for screening of GH-related disorders. Studies also have supported a possible relation between IGF-I levels and the risk and prognostic for some malignancies, besides a relation between IGF-I levels and mortality. Objective: As the determination of the IGF-I normal values for local populations is strongly desired, the aim of this investigation was to determine reference values for IGF-I using an immunoradiometric assay (IRMA) in an adult Brazilian population of Rio de Janeiro city, since there is no other study using this methodology in Brazilian population, and that this method is widely used in Brazil and worldwide. Materials and Methods: The study included samples of blood taken from 484 healthy subjects (251 men and 233 women) aged 18-70. The subjects agreed with this study, approved by the Ethical Committee of the Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti, Rio de Janeiro, Brazil. The samples were analyzed using a Diagnostic System Laboratories kit. For data analysis, age- and sex-specific figures were fitted after transformation of IGF-I values. Results: In adulthood, a slow age-dependent decrease was found. There was no significant difference in IGF-I values between men and women. Conclusion: This study established age-specific IGF-I reference values, for a healthy Brazilian adult population, determined by a widely IGF-I, IRMA used currently in Brazil.

Stereological tools in biomedical research

Stereological studies are more and more frequent in literature, particularly in the development/evolution, pathology, and neurosciences areas. The stereology challenge is to understand the structural inner threedimensional arrangement based on the analysis of the structure slices only showing two-dimensional information. Cavalieri and Scherle's methods to estimate volume, and Buffon's needle problem, are commented in the stereological context. A group of actions is needed to appropriately quantify morphological structures (unbiased and reproducibly), e.g. sampling, isotropic and uniform randomly sections (Delesse's principle), and updated stereological tools (disector, fractionator, nucleator, etc). Through the correct stereology use, a quantitative study with little effort could be performed: efficiency in stereology means a minimum slices sample counting (little work), low cost (slices preparation), but good accuracy. In the present text, a short review of the main stereological tools is done as a background basis to non-expert scientists

Simple hyperplasia versus proliferative endometrium: stereological study

The diagnosis of some forms of hyperplastic endometrium continues to present difficulties for the practicing pathologist. One of the major problems is the lack of a standard terminology for endometrial classification. Therefore, morphometrical techniques could help the accurate diagnosis. Thirteen samples of endometrium with simple hyperplasia and thirteen samples of proliferative endometrium were analyzed by light microscopy and stereology. We determined the volume density, the surface density and the length density (Vv, Sv, Lv) of the glands (epithelium and lumen) and the stroma. Volume densities of the epithelium and lumen as well as the surface density of the inner perimeter of the glands were greater in simple hyperplasia than in proliferative endometrium (p < 0.05). But the volume density of the stroma was greater in proliferative endometrium than in simple hyperplasia (p < 0.05). The length density of the glands and the surface density of the outer perimeter were not different comparing these two groups. Present results agree with previous studies that have pointed out the importance of quantitative parameters in the diagnosis of the endometrial pathologies offering new stereological parameters to this analysis

Papel da óxido nítrico sintase na etiopatogenia da estenose hipertrófica do piloro na infância / Role of nitric oxide synthase in the etiopathogenesis of hypertrophic pyloric stenosis in infants

Objetivo: reproduzir, experimentalmente, em ratos por meio do inibidor da enzima óxido nítrico sintase (ONS - L-NAME), os achados histopatológicos correspondentes a estenose hipertrófica do piloro da infância (EHPI). Métodos: para reproduzir o modelo de inibição de ONS na produção de EHPI, administrou-se L-NAME em ratas grávidas, a partir do 14§ dia gestacional (grupo L-NAME), comparando-se com uma gestação de controle. Após o nascimento, todos os ratos do grupo L-NAME foram mantidos sob inibição da ONS até o 42§ de vida, quando foram sacrificados. Os filhotes da gestação de controle, em que nenhuma droga foi administrada, foram também sacrificados com 42 dias de vida. Os animais e as visceras foram analisados e pesados. A região foi preparada tecnicamente e observada em microscopia de luz. Resultados: em comparação com os animais de controle, os L-NAME tiveram peso corporal e instestinal menor e peso gástrico maior. Nos animais L-NAME a microscopia de luz evidênciou hipertrofia da camada circular do músculo liso do piloro. Conclusão: este trabalho reproduziu um modelo experimental de estudo da estenose hipertrófica do piloro e comprovou, neste modelo a associação da ausência da ON sintase na musculatura do piloro

Comparison between computed tomography and ultrasonography in the cerebral ventricles morphometry

Ventrículoas encefálicos fueron evaluados por CT y US en sujetos normales y en pacientes afectados de meningitis. La biometría y el análisis estadístico fueron ejecutados observando el índex ventricular (VI por ciento), los diámetros de los cuernos frontal y temporal del ventrículo lateral, y los diámetros de los ventrículos III y IV. Comparando los dos métodos diagnósticos, el coeficiente de correlación fue alto para el diámetro del ventrículo lateral (r=0,94) y para el VI (0,85). La sensibilidad de la US fue mejor que para la CT en la observación del diámetro del cuerno temporal. La US, por ser de alta precisión, de bajo costo y por emplear un equipamiento transportable, resulta un método útil para la investigación de los ventrículos cerebrales

Morfologia e reconstruçäo anatômica do nó e da artéria do nó sinoatrial no coraçäo de Rattus norvegicus / Morphology and anatomical reconstruction of the node and of the sinoatrial nodes artery in the heart of the Rattus norvegicus

O nó sinoatrial (NSA, o marcapasso cardíaco) foi estudado em 19 coraçoes de Rattus norvegicus. Os coraçoes foram fixados por perfusao, incluídos e secionados em série com 5 e 1Omum de espessura. Os cortes foram, observados em microscópio óptico e os cortes seriados da regiao do NSA de um coraçao foram projetados e desenhados com aumento de 70 vezes permitindo a realizaçao de reconstruçao anatômica em cera. O NSA no rato tem células pequenas que coram-se mais fracamente que o parede atrial direita, estas células estao imersas em abundante tecido conjuntivo. O modelo do NSA teve forma irregular e dimensoes reais de 1,02 x O,31 mm (porçao anterior), O,87 x O,22mm (porçao média) e O,76 x O,O9mm (porçao posterior), a espessura foi de O,6lmm. A artéria do NSA apresenta abundância de fibras elásticas em sua parede. Tem trajeto espiralado dentro do NSA e diâmetro interno médio de 25mum. As características do NSA do rato sao úteis em estudos anátomo-fisiológicos do marcapasso neste animal.

Estudo quantitativo em microscopia óptica de luz do gânglio pterigopalatino no rato / Light microscopical quantitative study of the pterygopalatine ganglion in rat

Determinaçoes morfométricas estereológicas foram feitas em microscopia óptica de cortes semifinos de gânglio pterigopalatino (GP) do rato. Os seguintes parâmetros do pericário foram analisados: diâmetro equatorial (D), densidade volumétrica (Vv), densidade da superfície por volume (Sv) e densidade numérica (Nv). Os resultados obtidos do estudo de três animais, foram (média + desvio padrao): D = 23,93 + 6,46 mum; Vv = 53,83 + 7,40 por cento; Sv = 0,173 + 0,026 mum1; Nv (x 10(-5)) = 5,38 + 1,26 mum(-3). Os gânglios parassimpáticos cranianos apresentam variaçoes na mesma espécie, e entre diferentes espécies, quanto ao Nv e o tamanho das células.