Effects of exposure to a cafeteria diet during gestation and after weaning on the metabolism and body weight of adult male offspring in rats

In the present study, we investigated whether maternal exposure to a cafeteria diet affects the metabolism and body composition of offspring and whether such an exposure has a cumulative effect during the lifetime of the offspring. Female rats were fed a control (CON) or a cafeteria (CAF) diet from their own weaning to the weaning of their offspring. At 21 d of age, male offspring were divided into four groups by diet during gestation and after weaning (CON-CON, CON-CAF, CAF-CON and CAF-CAF). Blood was collected from dams (after weaning) and pups (at 30 and 120 d of age) by decapitation. CAF dams had significantly greater body weight and adipose tissue weight and higher concentrations of total cholesterol, insulin and leptin than CON dams (Student’s t test). The energy intake of CAF rats was higher than that of CON rats regardless of the maternal diet (two-way ANOVA). Litters had similar body weights at weaning and at 30 d of age, but at 120 d, CON-CAF rats were heavier. At both ages, CAF rats had greater adipose tissue weight than CON rats regardless of the maternal diet, and the concentrations of TAG and cholesterol were similar between the two groups, as were blood glucose concentrations at 30 d of age. However, at 120 d of age, CAF rats were hyperglycaemic, hyperinsulinaemic and hyperleptinaemic regardless of the maternal diet. These findings suggest that maternal obesity does not modulate the metabolism of male offspring independently, modifying body weight only when associated with the intake of a cafeteria diet by the offspring

Interaction between perceived maternal care, anxiety symptoms, and the neurobehavioral response to palatable foods in adolescents

Studies in rodents have shown that early life trauma leads to anxiety, increased stress responses to threatening situations, and modifies food intake in a new environment. However, these associations are still to be tested in humans. This study aimed to verify complex interactions among anxiety diagnosis, maternal care, and baseline cortisol on food intake in a new environment in humans. A community sample of 32 adolescents and young adults was evaluated for: psychiatric diagnosis using standardized interviews, maternal care using the Parental Bonding Inventory (PBI), caloric consumption in a new environment (meal choice at a snack bar), and salivary cortisol. They also performed a brain fMRI task including the visualization of palatable foods vs. neutral items. The study found a three-way interaction between anxiety diagnosis, maternal care, and baseline cortisol levels on the total calories consumed (snacks) in a new environment. This interaction means that for those with high maternal care, there were no significant associations between cortisol levels and food intake in a new environment. However, for those with low maternal care and who have an anxiety disorder (affected), cortisol was associated with higher food intake; whereas for those with low maternal care and who did not have an anxiety disorder (resilient), cortisol was negatively associated with lower food intake. In addition, higher anxiety symptoms were associated with decreased activation in the superior and middle frontal gyrus when visualizing palatable vs. neutral items in those reporting high maternal care. These results in humans mimic experimental research findings and demonstrate that a combination of anxiety diagnosis and maternal care moderate the relationship between the HPA axis functioning, anxiety, and feeding behavior in adolescents and young adults

Thrifty-eating behavior phenotype at the food court : programming goes beyond food preferences

Introduction: Prenatal growth impairment leads to higher preference for palatable foods in comparison to normal prenatal growth subjects, which can contribute to increased body fat mass and a higher risk for developing chronic diseases in small-for-gestational-age (SGA) individuals throughout life. This study aimed to investigate the effect of SGA on feeding behavior in children and adolescents, as well as resting-state connectivity between areas related to reward, self-control, and value determination, such as orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DL-PFC), amygdala and dorsal striatum (DS). Methods: Caregivers and their offspring were recruited from two independent cohorts in Brazil (PROTAIA) and Canada (MAVAN). Both cohorts included anthropometric measurements, food choice tasks, and resting-state functional magnetic resonance imaging (fMRI) data. Results: In the Brazilian sample (17 ± 0.28 years, n=70), 21.4% of adolescents were classified as SGA. They exhibited lower monetary-related expenditure to buy a snack compared to controls in the food choice test. Decreased functional connectivity (n=40) between left OFC and left DL-PFC; and between right OFC and: left amygdala, right DS, and left DS were observed in the Brazilian SGA participants. Canadian SGA participants (14.9%) had non-significant differences in comparison with controls in a food choice task at 4 years old ( ± 0.01, n=315). At a follow-up brain scan visit (10.21 ± 0.140 years, n=49), SGA participants (28.6%) exhibited higher connectivity between the left OFC and left DL-PFC, also higher connectivity between the left OFC and right DL-PFC. We did not observe significant anthropometric neither nutrients’ intake differences between groups in both samples. Conclusions: Resting-state fMRI results showed that SGA individuals had altered connectivity between areas involved in encoding the subjective value for available goods and decision-making in both samples, which can pose them in disadvantage when facing food options daily. Over the years, the cumulative exposure to particular food cues together with the altered behavior towards food, such as food purchasing, as seen in the adolescent cohort, can play a role in the long-term risk for developing chronic noncommunicable diseases

Obesidade materna induzida pela dieta de cafeteria em ratas Wistar : parâmetros metabólicos e comportamentais relacionados à memória de longo-prazo nos filhotes machos

Existem evidências de que dietas compostas por níveis elevados de lipídeos e/ou car-boidratos contribuem para o desenvolvimento de doenças crônico-degenerativas e de déficit cognitivo. Entretanto, os mecanismos pelos quais a obesidade materna interfere na saúde da prole, especificamente no metabolismo e na memória de longo-prazo, ain-da são pouco claros. O objetivo deste trabalho foi investigar se a obesidade materna interfere no metabolismo e nos comportamentos relacionados à memória de longo-prazo de seus filhotes, e se há um efeito somatório com a exposição à dieta de cafete-ria no decorrer da vida da prole. Ratas foram alimentadas com dieta controle (CON) ou de cafeteria (CAF) desde o desmame até os 210 dias de vida, no desmame de sua pro-le. A partir do desmame, seus filhotes machos foram divididos em 4 grupos (CON-CON, CON-CAF, CAF-CON e CAF-CAF) para que todas as ninhadas ingerissem CON ou CAF, independentemente da dieta materna. As mães foram decapitadas no dia seguin-te ao desmame dos filhotes. Foi decapitada e analisada em tarefas comportamentais metade dos filhotes aos 30 dias de idade e, a outra metade, aos 120 dias. As mães CAF apresentaram maior peso corporal total e de tecido adiposo e maiores concentra-ções circulantes de colesterol total, insulina e leptina do que as mães CON. A ingestão calórica semanal dos filhotes que ingeriram CAF mostrou-se maior do que os que inge-riram CON, independentemente da dieta materna. As ninhadas apresentaram peso cor-poral igual no desmame e aos 30dias, porém aos 120dias, os filhotes que ingeriram CON-CAF tiveram aumento de peso em relação aos filhotes CON, independentemente da dieta materna destes. Porém, os filhotes CAF-CAF tiveram redução do peso corporal em relação aos CON-CAF na idade adulta. Aos 30 e 120 dias, os filhotes que ingeriram CAF apresentaram peso de tecido adiposo maior do que os que ingeriram CON, inde-pendentemente da dieta materna. Aos 30 e 120dias, a trigliceridemia e a colesterolemia estavam iguais entre os grupos, assim como a glicemia aos 30 dias. Porém, aos 120 dias, os filhotes que ingeriram CAF apresentaram hiperglicemia, assim como hiperlepti-nemia e hiperinsulinemia, independentemente da dieta materna. Aos 30 dias, todos os grupos que foram expostos à dieta de cafeteria em alguma etapa da vida apresentaram declínio no desempenho em uma ou nas duas tarefas relacionadas à memória de lon-go-prazo (Reconhecimento de objetos e Esquiva Inibitória step-down). Já aos 120 dias, o grupo CAF-CAF foi o único que mostrou piora no desempenho na tarefa de Reconhe-cimento de Objetos, e todos os grupos mostraram capacidade de aprendizado e memó-ria na tarefa de Esquiva Inibitória step-down. Esses dados sugerem que a dieta materna modula o peso corporal e comportamentos relacionados à memória de longo-prazo dos filhotes e que seus efeitos sofrem influência da dieta pós-natal da prole. Porém, novos estudos são necessários para elucidar os mecanismos envolvidos no desenvolvimento dessas alterações.There is evidence that diets containing high levels of lipids and / or carbohydrates con-tribute to the development of chronic degenerative diseases and cognitive impairment. However, the mechanisms by which maternal obesity affects health of offspring, specifi-cally in metabolism and long-term memory, are still unclear. The aim of this study was to investigate whether maternal obesity interferes with the metabolism and behavior related to long-term memory of their offspring, and if there is a summation effect with exposure to the cafeteria diet during the life of the offspring. Rats were fed a control diet (CON) or cafeteria (CAF) from weaning to 210 days old at weaning of their offspring. After wean-ing, their male offspring were divided into 4 groups (CON-CON, CON-CAF, CAF and CAF-CON-CAF) for all litters ingest CON or CAF, irrespective of maternal diet. Mothers were decapitated on the day following weaning of pups. Was decapitated and analyzed in behavioral tasks half the pups at 30 days of age and the other half at 120 days. CAF mothers had higher total body weight and adipose tissue and increased circulating con-centrations of total cholesterol, insulin and leptin than mothers CON. The weekly caloric intake of pups that ingested CAF was higher than those who ate CON, regardless of maternal diet. Litters showed body weight equal to weaning and 30days, but the 120dias, puppies who ate CON-CAF had weight gain compared to CON offspring, re-gardless of maternal diet these. However, the pups CAF-CAF had reduced body weight compared to CON-CAF adulthood. At 30 and 120 days, the puppies that ingested CAF showed greater weight of adipose tissue than those who ate CON, irrespective of ma-ternal diet. At 30 and 120dias, blood triglyceride and cholesterol were similar between groups, as well as blood glucose levels at 30 days. However, at 120 days, the puppies that ingested CAF showed hyperglycemia, as hiperlepti-nemia and hyperinsulinemia, irrespective of maternal diet. At 30 days, all groups were exposed to the cafeteria diet at some stage of life show a decline in performance in one or both tasks related to long-term memory (Recognition of objects and Dodge inhibitory step-down). Already at 120 days, the group CAF-CAF was the one who showed deterioration in performance in the task of Object Recognition, and all groups showed learning ability and memory in the inhibitory avoidance task step down. These data suggest that maternal diet modulates body weight and behaviors related to long-term memory of the puppies and their effects are influenced by postnatal diet offspring. However, further studies are needed to eluci-date the mechanisms involved in the development of these changes

Obesidade materna induzida pela dieta de cafeteria em ratas Wistar : parâmetros metabólicos e comportamentais relacionados à memória de longo-prazo nos filhotes machos

Existem evidências de que dietas compostas por níveis elevados de lipídeos e/ou car-boidratos contribuem para o desenvolvimento de doenças crônico-degenerativas e de déficit cognitivo. Entretanto, os mecanismos pelos quais a obesidade materna interfere na saúde da prole, especificamente no metabolismo e na memória de longo-prazo, ain-da são pouco claros. O objetivo deste trabalho foi investigar se a obesidade materna interfere no metabolismo e nos comportamentos relacionados à memória de longo-prazo de seus filhotes, e se há um efeito somatório com a exposição à dieta de cafete-ria no decorrer da vida da prole. Ratas foram alimentadas com dieta controle (CON) ou de cafeteria (CAF) desde o desmame até os 210 dias de vida, no desmame de sua pro-le. A partir do desmame, seus filhotes machos foram divididos em 4 grupos (CON-CON, CON-CAF, CAF-CON e CAF-CAF) para que todas as ninhadas ingerissem CON ou CAF, independentemente da dieta materna. As mães foram decapitadas no dia seguin-te ao desmame dos filhotes. Foi decapitada e analisada em tarefas comportamentais metade dos filhotes aos 30 dias de idade e, a outra metade, aos 120 dias. As mães CAF apresentaram maior peso corporal total e de tecido adiposo e maiores concentra-ções circulantes de colesterol total, insulina e leptina do que as mães CON. A ingestão calórica semanal dos filhotes que ingeriram CAF mostrou-se maior do que os que inge-riram CON, independentemente da dieta materna. As ninhadas apresentaram peso cor-poral igual no desmame e aos 30dias, porém aos 120dias, os filhotes que ingeriram CON-CAF tiveram aumento de peso em relação aos filhotes CON, independentemente da dieta materna destes. Porém, os filhotes CAF-CAF tiveram redução do peso corporal em relação aos CON-CAF na idade adulta. Aos 30 e 120 dias, os filhotes que ingeriram CAF apresentaram peso de tecido adiposo maior do que os que ingeriram CON, inde-pendentemente da dieta materna. Aos 30 e 120dias, a trigliceridemia e a colesterolemia estavam iguais entre os grupos, assim como a glicemia aos 30 dias. Porém, aos 120 dias, os filhotes que ingeriram CAF apresentaram hiperglicemia, assim como hiperlepti-nemia e hiperinsulinemia, independentemente da dieta materna. Aos 30 dias, todos os grupos que foram expostos à dieta de cafeteria em alguma etapa da vida apresentaram declínio no desempenho em uma ou nas duas tarefas relacionadas à memória de lon-go-prazo (Reconhecimento de objetos e Esquiva Inibitória step-down). Já aos 120 dias, o grupo CAF-CAF foi o único que mostrou piora no desempenho na tarefa de Reconhe-cimento de Objetos, e todos os grupos mostraram capacidade de aprendizado e memó-ria na tarefa de Esquiva Inibitória step-down. Esses dados sugerem que a dieta materna modula o peso corporal e comportamentos relacionados à memória de longo-prazo dos filhotes e que seus efeitos sofrem influência da dieta pós-natal da prole. Porém, novos estudos são necessários para elucidar os mecanismos envolvidos no desenvolvimento dessas alterações.There is evidence that diets containing high levels of lipids and / or carbohydrates con-tribute to the development of chronic degenerative diseases and cognitive impairment. However, the mechanisms by which maternal obesity affects health of offspring, specifi-cally in metabolism and long-term memory, are still unclear. The aim of this study was to investigate whether maternal obesity interferes with the metabolism and behavior related to long-term memory of their offspring, and if there is a summation effect with exposure to the cafeteria diet during the life of the offspring. Rats were fed a control diet (CON) or cafeteria (CAF) from weaning to 210 days old at weaning of their offspring. After wean-ing, their male offspring were divided into 4 groups (CON-CON, CON-CAF, CAF and CAF-CON-CAF) for all litters ingest CON or CAF, irrespective of maternal diet. Mothers were decapitated on the day following weaning of pups. Was decapitated and analyzed in behavioral tasks half the pups at 30 days of age and the other half at 120 days. CAF mothers had higher total body weight and adipose tissue and increased circulating con-centrations of total cholesterol, insulin and leptin than mothers CON. The weekly caloric intake of pups that ingested CAF was higher than those who ate CON, regardless of maternal diet. Litters showed body weight equal to weaning and 30days, but the 120dias, puppies who ate CON-CAF had weight gain compared to CON offspring, re-gardless of maternal diet these. However, the pups CAF-CAF had reduced body weight compared to CON-CAF adulthood. At 30 and 120 days, the puppies that ingested CAF showed greater weight of adipose tissue than those who ate CON, irrespective of ma-ternal diet. At 30 and 120dias, blood triglyceride and cholesterol were similar between groups, as well as blood glucose levels at 30 days. However, at 120 days, the puppies that ingested CAF showed hyperglycemia, as hiperlepti-nemia and hyperinsulinemia, irrespective of maternal diet. At 30 days, all groups were exposed to the cafeteria diet at some stage of life show a decline in performance in one or both tasks related to long-term memory (Recognition of objects and Dodge inhibitory step-down). Already at 120 days, the group CAF-CAF was the one who showed deterioration in performance in the task of Object Recognition, and all groups showed learning ability and memory in the inhibitory avoidance task step down. These data suggest that maternal diet modulates body weight and behaviors related to long-term memory of the puppies and their effects are influenced by postnatal diet offspring. However, further studies are needed to eluci-date the mechanisms involved in the development of these changes

Boletín oficial de la provincia de Santander: Época 2ª Año 1º Número 110 - 1912 Septiembre 11

A programação do metabolismo e do comportamento alimentar e a posterior exposição a alimentos hiperpalatáveis possivelmente expliquem o risco aumentado para doenças crônicas relacionadas à obesidade dos indivíduos com baixo peso ao nascer. Especificamente, as evidências indicam que essa população é mais propensa à resistência à insulina e ao dano hipocampal e que a associação de ambos pode explicar, em parte, a disfunção no controle alimentar e na saúde metabólica. Os indivíduos com restrição fetal do crescimento, portanto, seriam mais propensos ao ciclo vicioso da obesidade: desde a infância, são mais sensíveis à insulina e preferem alimentos hiperpalatáveis aos saudáveis; a maior ingestão desses alimentos induz progressivamente à resistência à insulina; a alteração na sinalização de insulina hipocampal prejudica a formação da memória alimentar e o controle inibitório frente a pistas alimentares; o maior consumo crônico de alimentos hiperpalatáveis rompe o equilíbrio e, consequentemente, surgem as doenças metabólicas relacionadas à obesidade na vida adulta. A proposta deste trabalho foi introduzir a hipótese do ciclo vicioso da obesidade em indivíduos nascidos com baixo peso, investigando, através de um delineamento translacional, se a resistência à insulina estaria associada ao processamento cognitivo diferencial frente às pistas alimentares nos indivíduos nascidos pequenos para a idade gestacional. (a) Primeiramente, verificou-se o ciclo vicioso da obesidade em um estudo com adolescentes saudáveis, representantes de todo o espectro de peso ao nascer, analisando se a resistência à insulina periférica estaria associada ao comprometimento da memória alimentar implícita e à desativação de áreas cerebrais associadas ao controle inibitório em resposta a imagens de alimentos hiperpalatáveis. (b) Após, verificou-se se o baixo peso ao nascer estaria associado a um comportamento alimentar obesogênico e à alteração do tamanho hipocampal e da sensibilidade à insulina em adolescentes. (c) Por fim, em um modelo de desnutrição gestacional em roedores, analisou-se se o baixo peso ao nascer modifica o estado metabólico, o comportamento alimentar e a função insulínica hipocampal, e se o consumo de alimentos hiperpalatáveis incrementaria essas mudanças. Uma carta ao editor e um artigo de revisão foram escritos com base nessas premissas. No estudo clinico, foi encontrada que a maior resistência à insulina está associada ao comprometimento da memória alimentar implícita e que quanto maior a resistência à insulina, maior ativação de áreas cerebrais associadas à atenção e menor ativação das associadas ao controle inibitório frente a imagens de alimentos hiperpalatáveis. Esse estudo também mostrou que o baixo peso ao nascer está associado a uma ingestão mais densamente calórica, ao comprometimento da memória alimentar implícita, à redução do volume do subículo hipocampal e que a resistência à insulina interage com o peso ao nascer ao modular a ingestão alimentar externa. Por fim, o estudo experimental evidenciou que o baixo peso ao nascer está associado ao aumento da fosforilação do receptor glutamatérgico hipocampal induzido por insulina, à resistência à insulina hipocampal e à menor ingestão e entropia do comportamento alimentar quando há mudança na previsibilidade alimentar. Além disso, o baixo peso ao nascer junto à ingestão crônica de dieta hiperpalatável está associado ao maior ganho de peso corporal e ao reconhecimento da novidade alimentar. Ao reunir essas evidências, esta tese aponta que a associação da resistência à insulina ao comprometimento hipocampal explica, em parte, a alteração do comportamento alimentar dos indivíduos nascidos com baixo peso. Em um ambiente repleto de pistas alimentares, a ruptura do controle cognitivo pode levar ao ganho de peso e comprometer a saúde metabólica desses sujeitos ao longo do tempo.Metabolic and feeding behavioral programming with subsequent exposure to hyperpalatable foods can possibly explain the increased risk for chronic diseases related to obesity in individuals with low birth weight. Evidence indicate that this population is more prone to insulin resistance and hippocampal damage and that their association may partly explain the dysfunction in feeding control and metabolic health. Individuals with fetal growth restriction, therefore, would be more prone to the vicious cycle of obesity, they are more sensitive to insulin and prefer to eat hyperpalatable foods over more healthy options since childhood; the increased intake of these foods progressively induces insulin resistance; the alteration in hippocampal insulin signaling impairs the formation of food memory and the inhibitory control towards food cues; the greater chronic consumption of hyperpalatable foods disrupts the balance, and consequently, metabolic diseases related to obesity appear in adult life. The purpose of this study was to introduce the hypothesis of the vicious cycle of obesity in low birth weight individuals, investigating, through a translational design, whether insulin resistance would be associated with differential cognitive processing of foods cues in individuals born small for gestational age. (a) First, the vicious cycle of obesity was verified in a study with healthy adolescents from the full birth weight spectrum, analyzing whether peripheral insulin resistance would be associated with eating memory compromising and deactivation of brain areas associated with inhibitory control in response to hyperpalatable foods pictures. (b) Afterwards, it was verified whether low birth weight would be associated with an obesogenic eating behavior and with changes in hippocampal size and insulin sensitivity in adolescents. (c) Finally, in a model of gestational malnutrition in rodents, it was analyzed whether low birth weight modifies metabolic status, eating behavior and hippocampal insulin function, and whether the consumption of hyperpalatable foods would exacerbate these changes. A letter to the editor and a review manuscript were written based on these assumptions. In the clinical study, it was found that higher insulin resistance is associated with inconsistencies in implicitly learned food preferences and that the greater the insulin resistance, the greater activation of brain areas associated with attention and the lower activation of those associated with inhibitory control facing hyperpalatable foods pictures. This study also showed that low birth weight is associated with higher caloric intake, inconsistencies in implicitly learned food preferences, reduced hippocampal subiculum volume, and that insulin resistance interacts with birth weight by modulating food intake. Finally, the experimental study showed that low birth weight is associated with increased phosphorylation of the hippocampal glutamatergic receptor induced by insulin, hippocampal insulin resistance and lower intake and feeding behavior entropy when there is a change in food predictability. In addition, low birth weight along with chronic intake of hyperpalatable diet is associated with greater body weight gain and the recognition of novel foods. In gathering this evidence, this thesis points out that the association between insulin resistance and changes in hippocampus partly explains the altered eating behavior of low birth weight subjects. In an environment full of food cues, the disruption in cognitive control may lead to weight gain and compromise the metabolic health of these subjects over time