Carla da Silva Benetti

Early life stress is associated with anxiety, increased stress responsivity and preference for “comfort foods” in adult female rats

Abstract Chronic stress increases anxiety and encourages intake of palatable foods as “comfort foods”. This effect seems to be mediated by altered function of the hypothalamic–pituitary–adrenal axis. In the current study, litters of Wistar rats were subjected to limited access to nesting material (Early-Life Stress group – ELS) or standard care (Control group) from postnatal day 2 to 9. In adult life, anxiety was assessed using the novelty-suppressed feeding test (NSFT), and acute stress responsivity by measurement of plasma corticosterone and ACTH levels. Preference for palatable foods was monitored by a computerized system (BioDAQ, Research Diets®) in rats receiving only regular chow or given the choice of regular and palatable diet for 30 days. ELS-augmented adulthood anxiety in the NSFT (increased latency to eat in a new environment; decreased chow intake upon return to the home cage) and increased corticosterone (but not ACTH) secretion in response to stress. Despite being lighter and consuming less rat chow, ELS animals ate more palatable foods during chronic exposure compared with controls. During preference testing, controls receiving long-term access to palatable diet exhibited reduced preference for the diet relative to controls exposed to regular chow only, whereas ELS rats demonstrated no such reduction in preference after prolonged palatable diet exposure. The increased preference for palatable foods showed by ELS animals may result from a habit of using this type of food to ameliorate anxiety.

Satiety assessment in neonatally handled rats

We have previously demonstrated that neonatal handling increases sweet food ingestion. In the present study, we examined whether food intake, using different kinds of food, is altered in neonatally handled animals, with or without inducing satiety using a sucrose solution. Abdominal fat, glycemia and hormones linked to appetite including leptin, ghrelin and insulin were also measured. We tested palatable food consumption in the homecage to verify whether environmental cues could influence ingestion. Nests of Wistar rats were either (1) non-handled or (2) handled (10 min/day). Handling was performed on days 1-10 after birth. When adults, rats were habituated to sweet food (Froot Loops, Kelloggs) and to palatable fiber pellets (Fiber One), Nestlé). Sweet food consumption was increased in the neonatally handled group, when tested in the homecage, and also in the satiety experiment. These rats displayed a satiety curve when compared to the control group, which ate less but constantly. Handled rats exposed to a sucrose solution decreased sweet food ingestion, which did not occur in the control group. When exposed to a food with complex carbohydrates, these differences disappeared. There were no differences in body weight, abdominal fat or in glycemia, as well as no differences in plasma levels of insulin or leptin. However, ghrelin was decreased in neonatally handled rats. Neonatally handled rats demonstrated an increased consumption of sweet food, satiety responses to sucrose, as well as decreased levels of plasma ghrelin. It is possible that signaling mechanisms related to satiety, both peripherally and/or centrally may contribute to these behavioral findings.

Both Food Restriction and High-Fat Diet during Gestation Induce Low Birth Weight and Altered Physical Activity in Adult Rat Offspring: The “Similarities in the Inequalities” Model

We have previously described a theoretical model in humans, called “Similarities in the Inequalities”, in which extremely unequal social backgrounds coexist in a complex scenario promoting similar health outcomes in adulthood. Based on the potential applicability of and to further explore the “similarities in the inequalities” phenomenon, this study used a rat model to investigate the effect of different nutritional backgrounds during gestation on the willingness of offspring to engage in physical activity in adulthood. Sprague-Dawley rats were time mated and randomly allocated to one of three dietary groups: Control (Adlib), receiving standard laboratory chow ad libitum; 50% food restricted (FR), receiving 50% of the ad libitum-fed dam’s habitual intake; or high-fat diet (HF), receiving a diet containing 23% fat. The diets were provided from day 10 of pregnancy until weaning. Within 24 hours of birth, pups were cross-fostered to other dams, forming the following groups: Adlib_Adlib, FR_Adlib, and HF_Adlib. Maternal chow consumption and weight gain, and offspring birth weight, growth, physical activity (one week of free exercise in running wheels), abdominal adiposity and biochemical data were evaluated. Western blot was performed to assess D2 receptors in the dorsal striatum. The “similarities in the inequalities” effect was observed on birth weight (both FR and HF groups were smaller than the Adlib group at birth) and physical activity (both FR_Adlib and HF_Adlib groups were different from the Adlib_Adlib group, with less active males and more active females). Our findings contribute to the view that health inequalities in fetal life may program the health outcomes manifested in offspring adult life (such as altered physical activity and metabolic parameters), probably through different biological mechanisms.

Could preference for palatable foods in neonatally handled rats alter metabolic patterns in adult life

Previous studies indicate that, in adulthood, neonatally handled rats consume more sweet food than nonhandled rats. The aim of the present study was to assess the effects of the chronic exposure to a palatable diet (chocolate) in adult neonatally handled rats. We measured the consumption of foods (standard lab chow and chocolate), body weight gain, abdominal fat deposition, and levels of plasma lipids, glucose, insulin, and corticosterone in adult neonatally handled (10 min/d, first 10 d of life) and nonhandled rats. We found an increased intake of chocolate in handled rats, but this consumption decreased over time. Handled male animals exhibited higher body weight, higher caloric efficiency, and lower triglyceride levels. Nonhandled females that were exposed long-term to the highly caloric diet had increased abdominal fat deposition compared with handled females. Overall female rats had increased abdominal fat deposition, higher total cholesterol and glucose levels, and lower insulin in comparison with males. Interestingly, chocolate consumption diminished the weight of the adrenal glands in both handled and nonhandled animals. These findings suggest that neonatal handling induces a particular metabolic pattern that is sex specific.

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 (Students 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.

Effects of a chronic exposure to a highly palatable diet and its withdrawal, in adulthood, on cerebral Na+,K+-ATPase and plasma S100B in neonatally handled rats.

We have previously demonstrated that early environment influences the metabolic response, affecting abdominal fat deposition in adult female rats exposed to a long‐term highly caloric diet. In the present study, our goal was to verify the effects of the chronic exposure, in adulthood, to a highly palatable diet (chocolate) on cerebral Na+,K+‐ATPase activity and S100B protein concentrations, and the response to its withdrawal in neonatally handled and non‐handled rats. We measured the consumption of foods (standard lab chow and chocolate), body weight gain, S100B protein concentrations, as well as cerebral Na+,K+‐ATPase activity during chronic exposure and after chocolate withdrawal in adult female rats that had been exposed or not to neonatal handling (10 min/day, 10 first days of life). Non‐handled rats chronically exposed to chocolate exhibited increased plasma S100B levels, but there was no difference in abdominal fat S100B concentration between groups. Chronic chocolate consumption decreased Na+,K+‐ATPase activity in both amygdala and hippocampus in non‐handled, but not in handled rats, and this effect disappeared after chocolate withdrawal. Non‐handled animals also demonstrated increased frequency of head shaking in the open field after 24 h of chocolate withdrawal in comparison to handled ones. These findings suggest that neonatal handling modifies the vulnerability to metabolic and brain alterations induced by chronic exposure to a highly palatable diet in adulthood.

Variations in the neonatal environment modulate adult behavioral and brain responses to palatable food withdrawal in adult female rats

Early handling alters adult behavioral responses to palatable food and to its withdrawal following a period of chronic exposure. However, the central mechanisms involved in this phenomenon are not known. Since neonatal handling has persistent effects on stress and anxiety responses, we hypothesized that its involvement in the aforementioned association may be associated with differential neuroadaptations in the amygdala during withdrawal periods.

Neonatal environmental intervention alters the vulnerability to the metabolic effects of chronic palatable diet exposure in adulthood

Abstract Previous studies have demonstrated that early environmental interventions influence the consumption of palatable food and the abdominal fat deposition in female rats chronically exposed to a highly caloric diet in adulthood. In this study, we verified the metabolic effects of chronic exposure to a highly palatable diet, and determine the response to its withdrawal in adult neonatally handled and non-handled rats. Consumption of foods (standard lab chow and chocolate), body weight gain, abdominal fat deposition, plasma triglycerides, and leptin, as well as serum butyrylcholinesterase (BuChE), and cerebral acetylcholinesterase (AChE) activities were measured during chronic chocolate exposure and after deprivation of this palatable food in female rats exposed or not to neonatal handling (10 minutes/day, 10 first days of life). Handled rats increased rebound chocolate consumption in comparison to non-handled animals after 1 week of chocolate withdrawal; these animals also decreased body weight in the first 24 hours but this effect disappeared after 7 days of withdrawal. Chocolate increased abdominal fat in non-handled females, and this effect remained after 30 days of withdrawal; no differences in plasma leptin were seen after 7 days of withdrawal. Chocolate also increased serum BuChE activity in non-handled females, this effect was still evident after 7 days of withdrawal, but it disappeared after 30 days of withdrawal. Chocolate deprivation decreased cerebral AChE activity in both handled and non-handled animals. These findings suggest that neonatal handling modulates the preference for palatable food and induces a specific metabolic response that may be more adaptive in comparison to non-handled rats.

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

doi:10.1017/S0007114513003838, Published by Cambridge University Press, 13 December 2013. In Table 3 of Mucellini et al., the data were given wrongly. The results of body weight at 30 d were in place of visceral fat weight at 30 d. The results of the visceral fat weight at 30 d were in place of the retroperitoneal fat weight at 30 d. The results of the weight of the retroperitoneal fat at 30 d were in place of the body weight at 30 d. Finally, the results of the visceral fat weight at 120 d and the retroperitoneal fat weight at 120 d were corrected by dividing by 100.

Chocolate and Withdrawal

Evidence has indicated palatable foods and sugar as potential addictive substances because they induce effects on the mesolimbic reward system consistent with those promoted by drugs of abuse. Bingeing on sugar increases the release of neurotransmitters from brain structures involved in the regulation of appetite and/or addictive behaviors. Experimental models have demonstrated that excessive sugar consumption stimulates dopamine releasing in the nucleus accumbens as well as modifies dopamine receptors binding in the accumbens and striatum. Similar findings were detected in drug-dependent individuals. Abstinence of palatable food precipitates withdrawal symptoms, altering neurochemical homeostasis of the opioid pathway, and these effects, like opiate withdrawal, can be also seen when drugs of abuse are removed. Besides neuronal modifications produced in response to palatable food withdrawal, addiction-like behaviors have been described in some studies as well. Spontaneous withdrawal signs, like anxiety, teeth chattering, and aggressive behavior, are induced by palatable food (such as chocolate) deprivation. The interaction between genes and environment has a determining role in the individual tendency to eating disorders and metabolic diseases in adulthood. The neonatal environment seems to be a modulator of the vulnerability to palatable food addiction and withdrawal signs at the behavioral and neurochemical level in response to its deprivation.