RESUMO
Maternal obesity may trigger long-term neurodevelopmental disorders in offspring. Considering the benefits of the Brazil nut (Bertholletia excelsa H.B.K.), a rich source of nutrients such as selenium, this study aimed to evaluate its effect on the behavior of obese rat offspring and its relationship with oxidative stress. From 60 days of age until weaning, female Wistar rats were fed a high-fat diet (mHF) or an HF diet supplemented with 5% Brazil nut (mHF/BN), while control mothers (mCTL) were fed a standard diet or a standard diet supplemented with 5% Brazil nut (mBN). Male pups received a standard diet throughout life and, at 30 and 90 days old, were subjected to behavioral tasks to evaluate anxiety and cognition. Biochemical evaluations were performed at 90 days of age. No alterations were observed in the anxiety behavior of the offspring. However, the offspring of the mHF group (oHF) exhibited impaired short-term memory at 30 and 90 days of age and impaired long-term memory at 30 days. Short-term memory impairment was prevented by Brazil nuts in young rats (30 days). While the serum selenium concentration was reduced in the oHF group, the serum catalase concentration was reduced in all groups, without changes in lipid peroxidation or protein carbonylation. Brazil nut maternal diet supplementation prevented short- and long-term cognitive impairment in the offspring, which may be related to the selenium levels.
Assuntos
Bertholletia , Disfunção Cognitiva , Selênio , Humanos , Feminino , Masculino , Ratos , Animais , Gravidez , Ratos Wistar , Obesidade , Suplementos Nutricionais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Dieta Hiperlipídica/efeitos adversosRESUMO
Herein, we assessed milk hormones, the biochemical composition of milk, and its association with neonatal body weight gain and metabolic homeostasis in weaned rats whose mothers were undernourished in the last third of pregnancy. From the 14th day of pregnancy until delivery, undernourished mothers had their food restricted by 50% (FR50), whereas control mothers were fed ad libitum. The litter size was adjusted to eight pups, and rats were weaned at 22 days old. Milk and blood from mothers, as well as blood and tissues from pups, were collected for further analyses. At birth, FR50 pups were smaller than control pups, and they exhibited hyperphagia and rapid catch-up growth during the suckling period. On day 12, the milk from FR50 mothers had higher energy content, glucose, total cholesterol, triglycerides, and acylated ghrelin but lower leptin and corticosterone levels. Interestingly, FR50 mothers were hypoglycemic and hyperleptinemic at the end of the nursing period. Weaned FR50 pups had an obese phenotype and exhibited insulin resistance, which was associated with hyperglycemia and hypertriglyceridemia; they also had high blood levels of total cholesterol, leptin, and acylated ghrelin. In addition, the protein expression of growth hormone secretagogue receptor (GHSR) in the hypothalamus was increased by almost 4-fold in FR50 pups. In summary, maternal calorie restriction during the last third of pregnancy disrupts energy and metabolic hormones in milk, induces pup hyperleptinemia and hyperghrelinemia, and upregulates their hypothalamic GHSR, thus suggesting that the hypothalamic neuroendocrine circuitry may be working to address the early onset of obesity.
Assuntos
Leptina , Desnutrição , Animais , Peso Corporal/fisiologia , Colesterol , Feminino , Grelina , Desnutrição/complicações , Leite , Obesidade , Gravidez , Ratos , Ratos WistarRESUMO
A growing body of evidence highlights that several insults during pregnancy impact the vascular function and immune response of the male and female offspring. Overactivation of the immune system negatively influences cardiovascular function and contributes to cardiovascular disease. In this review, we propose that modulation of the immune system is a potential link between prenatal stress and offspring vascular dysfunction. Glucocorticoids are key mediators of stress and modulate the inflammatory response. The potential mechanisms whereby prenatal stress negatively impacts vascular function in the offspring, including poor hypothalamic-pituitary-adrenal axis regulation of inflammatory response, activation of Th17 cells, renin-angiotensin-aldosterone system hyperactivation, reactive oxygen species imbalance, generation of neoantigens and TLR4 activation, are discussed. Alterations in the immune system by maternal stress during pregnancy have broad relevance for vascular dysfunction and immune-mediated diseases, such as cardiovascular disease.
RESUMO
Nutritional insults early in life have been associated with metabolic diseases in adulthood. We aimed to evaluate the effects of maternal food restriction during the suckling period on metabolism and interscapular brown adipose tissue (iBAT) thermogenically involved proteins in adult rat offspring. Wistar rats underwent food restriction by 50% during the first two-thirds of lactation (FR50 group). Control rats were fed ad libitum throughout lactation (CONT group). At birth, the litter size was adjusted to eight pups, and weaning was performed at 22 days old. Body weight and food and water intake were assessed every two days. High- (HCD, 4,589 cal) and normal-caloric diet (NCD, 3,860 cal) preferences, as well as food intake during the dark part of the cycle, were assessed. At 100 days old, the rats were euthanized, and blood and tissues were removed for further analyses. Adult FR50 rats, although hyperphagic and preferring to eat HCD (P<.001), were leaner (P<.001) than the CONT group. The FR50 rats, were normoglycemic (P=.962) and had hypertriglyceridemia (P<.01). In addition, the FR50 rats were dyslipidemic (P<.01), presenting with a high atherogenic risk by the Castelli indexes (P<.01), had a higher iBAT mass (P<.01), fewer ß3 adrenergic receptors (ß3-AR, P<.05) and higher iBAT expression of uncoupled protein 1 (UCP1, P<.05) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, P<.001) than the CONT rats. In conclusion, maternal food restriction during early breastfeeding programs rat offspring to have a lean phenotype, despite hyperphagia, and increased iBAT UCP1 and PGC-1α protein expression.
Assuntos
Tecido Adiposo Marrom/metabolismo , Aleitamento Materno , Lactação/metabolismo , Termogênese , Magreza/metabolismo , Animais , Restrição Calórica , Metabolismo Energético , Feminino , Humanos , Masculino , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Fenótipo , Ratos , Ratos Wistar , Receptores Adrenérgicos beta 3/genética , Receptores Adrenérgicos beta 3/metabolismo , Magreza/genética , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismoRESUMO
Metformin is an antidiabetic drug used for the treatment of diabetes and metabolic diseases. Imbalance in the autonomic nervous system (ANS) is associated with metabolic diseases. This study aimed to test whether metformin could improve ANS function in obese rats. Obesity was induced by neonatal treatment with monosodium L-glutamate (MSG). During 21-100 days of age, MSG-rats were treated with metformin 250 mg/kg body weight/day or saline solution. Rats were euthanized to evaluate biometric and biochemical parameters. ANS electrical activity was recorded and analyzed. Metformin normalized the hypervagal response in MSG-rats. Glucose-stimulated insulin secretion in isolated pancreatic islets increased in MSG-rats, while the cholinergic response decreased. Metformin treatment normalized the cholinergic response, which involved mostly the M3 muscarinic acetylcholine receptor (M3 mAChR) in pancreatic beta-cells. Protein expression of M3 mAChRs increased in MSG-obesity rats, while metformin treatment decreased the protein expression by 25%. In conclusion, chronic metformin treatment was effective in normalizing ANS activity and alleviating obesity in MSG-rats.
Assuntos
Sistema Nervoso Autônomo/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Obesidade/tratamento farmacológico , Acetilcolina/farmacologia , Animais , Glucose/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Masculino , Neostigmina/farmacologia , Obesidade/induzido quimicamente , Obesidade/metabolismo , Obesidade/fisiopatologia , Ratos Wistar , Receptor Muscarínico M3/metabolismo , Glutamato de Sódio , Nervo Vago/efeitos dos fármacos , Nervo Vago/fisiologiaRESUMO
NEW FINDINGS: What is the central question of this study? Studies reported the efficacy of metformin as a promising drug for preventing or treating of metabolic diseases. Nutrient stresses during neonatal life increase long-term risk for cardiometabolic diseases. Can early metformin treatment prevent the malprogramming effects of early overfeeding? What is the main finding and its importance? Neonatal metformin treatment prevented early overfeeding-induced metabolic dysfunction in adult rats. Inhibition of early hyperinsulinaemia and adult hyperphagia might be associated with decreased metabolic disease risk in these animals. Therefore, interventions during infant development offer a key area for future research to identify potential strategies to prevent the long-term metabolic diseases. We suggest that metformin is a potential tool for intervention. ABSTRACT: Given the need for studies investigating the possible long-term effects of metformin use at crucial stages of development, and taking into account the concept of metabolic programming, the present work aimed to evaluate whether early metformin treatment might program rats to resist the development of adult metabolic dysfunctions caused by overnutrition during the neonatal suckling phase. Wistar rats raised in small litters (SLs, three pups per dam) and normal litters (NLs, nine pups per dam) were used as models of early overfeeding and normal feeding, respectively. During the first 12 days of suckling, animals from SL and NL groups received metformin, whereas the controls received saline injections. Food intake and body weight were monitored from weaning until 90 days of age, when biometric and biochemical parameters were assessed. The metformin treatment decreased insulin concentrations in pups from SL groups, and as adults, these animals showed improvements in glucose tolerance, insulin sensitivity, body weight gain, white fat pad stores and food intake. Low-glucose insulinotrophic effects were observed in pancreatic islets from both NL and SL groups. These results indicate that early postnatal treatment with metformin inhibits early overfeeding-induced metabolic dysfunctions in adult rats.
Assuntos
Ilhotas Pancreáticas/efeitos dos fármacos , Doenças Metabólicas/prevenção & controle , Metformina/farmacologia , Hipernutrição/tratamento farmacológico , Tecido Adiposo Branco/metabolismo , Animais , Animais Recém-Nascidos , Glicemia/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Feminino , Insulina/metabolismo , Resistência à Insulina/fisiologia , Ilhotas Pancreáticas/metabolismo , Leptina/metabolismo , Masculino , Doenças Metabólicas/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Hipernutrição/metabolismo , Ratos , Ratos Wistar , Aumento de Peso/efeitos dos fármacosRESUMO
Objective: This study aimed to investigate the root canal system morphology of maxillary first molar mesiobuccal (MB) roots in a Brazilian sub-population using micro-computed tomography. Methods: Ninety-six MB roots were scanned with a micro-CT (Skyscan 1173, Bruker). Three-dimensional images were analyzed regarding the number of pulp chamber orifices, the number and classification of the canals, the presence of accessory canals in different thirds of the root as well as the number and type of apical foramina. Results: A single entrance orifice was found in 53.0% of the samples, two in 43.9% and only 3.1% had three orifices. The second mesiobuccal root canal (MB2) was present at some portion of the root in 87.5% of the specimens. A single apical foramen was present in 16.7%, two in 22.9%, and three or more foramina in 60.4% of the roots. Only 55.3% and 76.1% of the root canals could be arranged by Weine's and Vertucci's classifications, respectively. Conclusion: The number of orifices at the pulp chamber level could not work as a predictor of the MB2 presence. The most prevalent canal configuration was Weine type IV / Vertucci type V. The anatomical complexity of the MB root could not be entirely classified by the current most accepted classifications.
Assuntos
Cavidade Pulpar/diagnóstico por imagem , Imageamento Tridimensional/métodos , Maxila/diagnóstico por imagem , Dente Molar/diagnóstico por imagem , Raiz Dentária/diagnóstico por imagem , Microtomografia por Raio-X/métodos , Brasil , Humanos , Ápice Dentário/diagnóstico por imagemRESUMO
Currently, metabolic disorders are one of the major health problems worldwide, which have been shown to be related to perinatal nutritional insults, and the autonomic nervous system and endocrine pancreas are pivotal targets of the malprogramming of metabolic function. We aimed to assess glucose-insulin homeostasis and the involvement of cholinergic responsiveness (vagus nerve activity and insulinotropic muscarinic response) in pancreatic islet capacity to secrete insulin in weaned rat offspring whose mothers were undernourished in the first 2 weeks of the suckling phase. At delivery, dams were fed a low-protein (4% protein, LP group) or a normal-protein diet (20.5% protein, NP group) during the first 2 weeks of the suckling period. Litter size was adjusted to six pups per mother, and rats were weaned at 21 days old. Weaned LP rats presented a lean phenotype (P < 0.01); hypoglycaemia, hypoinsulinaemia and hypoleptinaemia (P < 0.05); and normal corticosteronaemia (P > 0.05). In addition, milk insulin levels in mothers of the LP rats were twofold higher than those of mothers of the NP rats (P < 0.001). Regarding glucose-insulin homeostasis, weaned LP rats were glucose-intolerant (P < 0.01) and displayed impaired pancreatic islet insulinotropic function (P < 0.05). The M3 subtype of the muscarinic acetylcholine receptor (M3mAChR) from weaned LP rats was less responsive, and the superior vagus nerve electrical activity was reduced by 30% (P < 0.01). A low-protein diet in the suckling period malprogrammes the vagus nerve to low tonus and impairs muscarinic response in the pancreatic ß-cells of weaned rats, which are imprinted to secrete inadequate insulin amounts from an early age.
Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Ilhotas Pancreáticas/embriologia , Desnutrição/fisiopatologia , Fenômenos Fisiológicos da Nutrição Materna , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Animais , Glicemia/análise , Células Cultivadas , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Dieta com Restrição de Proteínas/efeitos adversos , Feminino , Glucose/metabolismo , Teste de Tolerância a Glucose , Insulina/metabolismo , Células Secretoras de Insulina , Ilhotas Pancreáticas/inervação , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/fisiopatologia , Lactação/fisiologia , Masculino , Desnutrição/etiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Cultura Primária de Células , Ratos , Ratos Wistar , Nervo Vago/fisiopatologia , DesmameRESUMO
The worldwide increase in metabolic diseases has urged the scientific community to improve our understanding about the mechanisms underlying its cause and effects. A well supported area of studies had related maternal stress with early programming to the later metabolic diseases. Mechanisms upon origins of metabolic disturbances are not yet fully understood, even though stressful factors rising glucocorticoids have been put out as pivotal trigger by programming metabolic diseases as long-term consequence. Considering energy balance and glucose homeostasis, by producing and/or sensing regulator signals, hypothalamus-pituitary-adrenal axis and endocrine pancreas are directly affected by glucocorticoids excess. We focus on the evidences reporting the role of increased glucocorticoids due to perinatal insults on the physiological systems involved in the metabolic homeostasis and in the target organs such as endocrine pancreas, white adipose tissue and blood vessels. Besides, we review some mechanisms underlining the malprogramming of type 2 diabetes, obesity and hypertension. Studies on this field are currently ongoing and even there is a good understanding regarding the effects of glucocorticoids addressing metabolic diseases, few is known about the relationship between maternal insults rising glucocorticoids to pups' metabolic disturbances, a thorough understanding about that may provide pivotal clinical clues regarding those disorders.
Assuntos
Desenvolvimento Fetal , Glucocorticoides/metabolismo , Doenças Metabólicas/metabolismo , Adulto , Animais , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Humanos , Hipertensão/metabolismo , Obesidade/metabolismo , GravidezRESUMO
Objectives: We aimed to assess the effects of a maternal protein-caloric restriction diet during late pregnancy on the metabolism of rat offspring fed a high-fat diet (HFD) during adulthood.Methods: During late pregnancy, rat dams received either a low-protein (4%; LP group) or normoprotein (23%; NP group) diet. After weaning, the offspring were fed a standard diet (Control; C). Male offspring (60 days old) from both groups were then fed either the C diet or HFD until they were 90 days old. The adult offspring and maternal metabolic parameters and autonomic nervous system (ANS) were then evaluated.Results: Dams exhibited low body weight gain and food intake during the LP diet consumption. At lactation, these dams showed high body weight gain, hypoinsulinemia and hyperglycemia. The maternal LP diet resulted in low body weights for the pups. There were also no differences in the metabolic parameters between the adult LP offspring that were fed the C diet and the NP group. Adults of both groups that were fed the HFD developed obesity associated with altered insulin/ glucose homeostasis and altered ANS activity; however, the magnitudes of these parameters were higher in the LP group than in the NP group.Conclusions: Maternal protein malnutrition during the last third of pregnancy malprograms the metabolism of rat offspring, resulting in increased vulnerability to HFD-induced obesity, and the correlated metabolic impairment might be associated with lower sympathetic nerve activity in adulthood.