RESUMO
Three relevant, interrelated scientific advances are described: the concept of critical periods (CPs), the Barker Hypothesis (BH), and the underlying epigentic mechanisms involved. Critical periods are genetically programmed, highly sensitive time intervals during which the interaction between environment and individuals generates the development of physiological processes related to physical growth and development, survival (breastfeeding), social behavior, and learning. Barker hypothesis is based on the finding that prenatal malnutrition (for example, lowbirthweight) is closely related to mortality due to cardiovascular disease CVD) in the adult, and to the risk conditions leading to it: insuline resistence, metabolic syndrome, obesity, and high blood pressure. This association is no due to genetical causes, but secondary to nutritional deficits which in turn generate epigenetic mechanisms of methylation of DNA basis and cromatine proteines (histones), which do not modify the genetic code but modulate its expresion, reinforcing some genes, inhibiting others, regulating when and where they are expressed. These genes participate in the process called programming, consisting of permanent changes in the response to stimulation of metabolic and hormone regulators, such as, for example, increasing insuline resistence. Epigenetic changes persist even when original conditions (fetal or perinatal malnutrition) are no longer present. This, in turn, affects health of the offspring later in adult life, creating thus the same environmental prenatal conditions to the next generation. This transgenerational effects of early nutritional experiences are more frequent in population groups of por socioeconomic level, and consequently have serious implications in the future health of Latin American populations.
Se describen tres adelantos interrelacionados: el concepto de períodos críticos, la hipótesis de Barker y los mecanismos epigenéticos involucrados. Los primeros son intervalos temporales genéticamente programados, vinculados a procesos fisiológicos ligados al crecimiento y desarrollo físico del individuo (habilitación de vías nerviosas, replicación neuronal), a procesos relacionados con el apego madre-hijo, la lactancia, la socialización y el aprendizaje. La hipótesis de Barker sostiene que la desnutrición, en la etapa perinatal, se asocia a mayor mortalidad por enfermedad cardiovascular y a las alteraciones metabólicas que condicionan dicha enfermedad (síndrome metabólico, resistencia a la insulina, hipertensión). Esta asociación es secundaria a las alteraciones nutricionales que desencadenan mecanismos epigenéticos de metilación de bases del ADN o de histonas. Los cambios epigenéticos son permanentes y pueden tener efectos transgeneracionales, al afectar el ambiente perinatal en donde crece la descendencia, hecho relevante en países con poblaciones que viven en condiciones socioeconómicas desfavorables.
Assuntos
Epigênese Genética , Complicações na Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adulto , Feminino , Humanos , Distúrbios Nutricionais/epidemiologia , Distúrbios Nutricionais/genética , Fenômenos Fisiológicos da Nutrição , Estado Nutricional , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fatores de TempoRESUMO
An experiment on rat undernutrition through seven generations was performed in order to see: (1) whether the nutritional stress on growth increases from one generation to the next, and (2) if an equilibrium point (AFP) in which the RFI--the amount of food intake (mg) per gram of body weight--reached is the same in both control and undernourished animals. The RFI values were calculated for each generation, between the 30th and 100th days of age. A moderate undernutrition was applied to the seven generations (F1 to F7) following the parental (P) one, which acted as controls. Undernourishment was made from conception to the end of the experiment (100 days old). The RFI values diminished with the age increment and increased through generations. There was, however, a clear AFP of 75.9 +/- 3.5 mg/g at 100 days of age in males, and of 78.7 +/- 4.2 mg/g at 90 days of age in females. A clear cumulative increment of RFI through the filial generations was also found at intermediate growth ages. The frequently argued nongenetic transmission of the nutritional deficiencies from parents to descendants was corroborated with the present results. Such cumulative effect was evident at ages before the AFP was reached; i.e., when the decrement in body mass of the undernourished animals was not yet equilibrated with the amount of available nutrients.
Assuntos
Ingestão de Alimentos/fisiologia , Distúrbios Nutricionais/genética , Distúrbios Nutricionais/fisiopatologia , Envelhecimento/fisiologia , Análise de Variância , Animais , Peso Corporal , Feminino , Crescimento , Masculino , Distúrbios Nutricionais/patologia , Pais , Ratos , Ratos Wistar , Caracteres Sexuais , Fatores de TempoRESUMO
Malnutrition induces profound deleterious effects on several metabolic and neuroendocrine functions. In the present study, we examined the impact of maternal food restriction, during gestation and lactation, on the metabolic-neuroendocrine function of their male offspring at 21 and 60 d of age. Well-nourished (WN) and undernourished (UN) pregnant rats were used, during gestation and lactation, until pups were weaned. Twenty-one-day-old WN and UN male pups were studied in basal and postinsulin conditions. Additional groups of weaned (WN and UN) male rats were fed either ad libitum (WN-WN and UN-WN) or in a restricted fashion (WN-UN and UN-UN) until experimentation at age 60 d. Body weights of mothers and their male offspring were monitored. Basal and postinsulin plasma concentrations of several metabolic fuels were evaluated. Our results indicate that 21-d-old UN male rats exhibited (vs their WN counterparts), decreased body weights, similar basal and postinsulin glycemia, similar basal plasma adrenocorticotropic hormone (ACTH) and corticosterone levels but diminished ACTH response to insulin treatment, and basal hypoleptinemia and significant insulin-induced leptin release. Finally, at 60 d of age, long-term UN (WN-UN and UN-UN) rats showed lower plasma (basal and postinsulin) glucose, and basal triglyceride levels than their counterparts (WN-WN and UN-WN). Sixty-day-old rats submitted to either food restriction protocol also showed a reduced hypothalamo-pituitary-adrenal axis response to insulin-induced hypoglycemia and basal hypoleptinemia, in spite of restoration of normal body weights. These results further indicate a clear metabolic-neuroendocrine dysfunction in male pups of UN mothers, with the abnormality partially present at weaning and deteriorated by adulthood, even after the recovery of normal body weight. Our study strongly supports the importance of the irreversibility of a deleterious allostatic state resulting from fetal and early postnatal undernutrition.
Assuntos
Adipócitos/metabolismo , Sistema Hipotálamo-Hipofisário/fisiologia , Distúrbios Nutricionais/genética , Sistema Hipófise-Suprarrenal/fisiologia , Hormônio Adrenocorticotrópico/sangue , Animais , Glicemia/metabolismo , Proteínas Sanguíneas/metabolismo , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Feminino , Glucocorticoides/sangue , Hipoglicemia/sangue , Lactação/fisiologia , Leptina/sangue , Masculino , Gravidez , Ratos , Ratos Endogâmicos F344 , Triglicerídeos/sangueRESUMO
La obesidad es uno de los trastornos nutricionales más frecuentes en los países desarrollados, de tal manera que se considera un problema de salud pública, En los países subdesarrollados, este problema se ha incrementado en los últimos años, tanto en los estratos altos como bajos de la población. En Venezuela, en el año 1994, el Sistema de Vigilancia Alimentaria y Nutricional (SISVAN) del Instituto Nacional de Nutrición (INN) reportó un 10 por ciento de sobrepeso, de acuerdo al indicador Peso para la Talla (P/T). Se entiende por obesidad el exceso de grasa corporal, por lo tanto es necesario cuantificar el tejido graso para hacer un diagnóstico preciso. Por todos estos señalamientos es fundamental la prevención y detección precoz, ya que la obesidad que se instaura en la infancia predispone a Enfermedad Crónica no Transmisible (ECNT) en la vida adulta
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Distúrbios Nutricionais/genética , Distúrbios Nutricionais/prevenção & controle , Distúrbios Nutricionais/psicologia , Obesidade/diagnóstico , Obesidade/genética , Obesidade/psicologiaRESUMO
Reviewed are reports on factors, identified by risk analysis, involved in the genesis of primary malnutrition in children. Data are compared with the sequence of factors in a flow diagram, based on the natural history of malnutrition, proposed 3 decades ago. Susceptibility to malnutrition is analyzed in light of observations related to inheritance, the ob gene and leptin.
Assuntos
Distúrbios Nutricionais/etiologia , Tecido Adiposo/metabolismo , Criança , Suscetibilidade a Doenças , Feminino , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Leptina , Exposição Materna , Distúrbios Nutricionais/genética , Gravidez , Proteínas/genética , Fatores de Risco , Fatores Socioeconômicos , Aumento de PesoRESUMO
Health effects from environmental toxicants may be a more serious problem in developing countries compared with developed countries because the problem is potentiated by other factors: a) the lack of or failure to enforce regulations, which allows human exposures to genotoxic agents; b) undernourishment of the lower economic and social classes that comprise the most exposed populations from industrial and agricultural activities; and c) parasitic infections that afflict a wide range of populations in both urban and rural areas. Data on the genotoxic effects of different types of exposures, including environmental exposes (natural and industrial), occupational exposures, and infections and medical treatments, are presented and discussed with the point of view that all these factors must be taken into account with respect to regulation and the protection of human health. Occupational exposures in developing countries are higher than in developed countries due to lack of stringent regulations, lack of knowledge of the risks involved, and the negligence of workers. General pollution is another important issue since developed countries have established strict regulations and risky industrial processes are being exported to developing countries, along with banned substances and dangerous industrial wastes. It should be emphasized that stringent regulations in developed countries will not prevent exposures in the long term because toxic substances that are released into the environment will ultimately reach all our future generations.
Assuntos
Países em Desenvolvimento , Exposição Ambiental/efeitos adversos , Grupos de População Animal , Animais , Antiparasitários/efeitos adversos , Antiparasitários/uso terapêutico , Encefalopatias/tratamento farmacológico , Encefalopatias/genética , Encefalopatias/parasitologia , Carcinógenos/efeitos adversos , Aberrações Cromossômicas , Cisticercose/tratamento farmacológico , Cisticercose/genética , Cisticercose/parasitologia , Poluentes Ambientais/efeitos adversos , Humanos , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Metronidazol/efeitos adversos , Metronidazol/uso terapêutico , Mutagênicos/efeitos adversos , Distúrbios Nutricionais/genética , Exposição Ocupacional/efeitos adversos , Praziquantel/efeitos adversos , Praziquantel/uso terapêutico , Troca de Cromátide Irmã , TaeniaRESUMO
The alkaline single cell gel (SCG) assay is a sensitive electrophoretic technique for detecting the presence of DNA single strand breaks and alkali-labile damage in individual cells. This technique was used to assess and compare the level of DNA damage in peripheral blood leukocytes/lymphocytes from well-nourished children with infection, well-nourished children with infection and under drug treatment, and from malnourished infected children with and without previous drug treatment. The present study shows that severe infection is associated with a significant increase in DNA damage. The average migration length was five times greater in severely infected well-nourished children compared to that found in healthy, well-nourished children. The results obtained in this study indicate that malnutrition is another factor associated with an increase in DNA migration. The average tail length for malnourished, severely infected children was twice as great as that obtained for cells from well-nourished, severely infected children. We also detected a variable increase in DNA migration associated with treatment for severe infection. Nevertheless, the excessive heterogeneity, the concurrent number of drugs used and the limited size of the treated population precludes an accurate assessment of which drugs were involved in the increase in DNA damage. Further studies will be necessary involving a large number of patients to address the relation between levels of DNA damage and specific kinds of infection, various drug treatments, and the type and severity of malnutrition. The increased level of DNA damage in severely infected and malnourished children could be related to negative effects such as a deficient immune response resulting in an increased susceptibility to malignant transformation.
Assuntos
Dano ao DNA , Infecções/genética , Distúrbios Nutricionais/genética , Criança , Pré-Escolar , Eletroforese , Feminino , Humanos , Lactente , Leucócitos/química , Linfócitos/química , MasculinoRESUMO
A kindred of four children of different ages was at the same time adopted and transferred from a very poor to a fairly good environment. A rapid catch-up growth was observed in all four during the first 2 years after adoption. Beyond the 2nd year, physical development varied according to age, sex, and the rhythm of sexual maturation. Puberty was not advanced. Final height depended mainly on the height at the onset of puberty. The homogeneity of this familial story can contribute to a better understanding of the age-related interactions between the nutritional and environmental conditions and the genetic factors in human development. The growth and puberty of children coming from poor areas of the world to be fostered in families living in industrialized countries may shed some light on the role of nutritional and environmental factors in human development.