Márcio Bonesso Alves

Increased palatable food intake and response to food cues in intrauterine growth-restricted rats are related to tyrosine hydroxylase content in the orbitofrontal cortex and nucleus accumbens.

Intrauterine growth restriction (IUGR) is associated with altered food preferences, which may contribute to increased risk of obesity. We evaluated the effects of IUGR on attention to a palatable food cue, as well as tyrosine hydroxylase (TH) content in the orbitofrontal cortex (OFC) and nucleus accumbens (NAcc) in response to sweet food intake. From day 10 of gestation and through lactation, Sprague-Dawley rats received either an ad libitum (Adlib) or a 50% food-restricted (FR) diet. At birth, pups were cross-fostered, generating four groups (gestation/lactation): Adlib/Adlib (control), FR/Adlib (intrauterine growth-restricted), Adlib/FR, and FR/FR. Adult attention to palatable food cues was measured using the Attentional Set-Shifting Task (ASST), which uses a sweet pellet as reward. TH content in the OFC and NAcc was measured at baseline and in response to palatable food intake. At 90 days of age, FR/Adlib males ate more sweet food than controls, without differences in females. However, when compared to Controls, FR/Adlib females needed fewer trials to reach criterion in the ASST (p=0.04) and exhibited increased TH content in the OFC in response to sweet food (p=0.03). In the NAcc, there was a differential response of TH content after sweet food intake in both FR/Adlib males and females (p<0.05). Fetal programming of adult food preferences involves the central response to palatable food cues and intake, affecting dopamine release in select structures of the brain reward system.

Intrauterine growth restriction increases the preference for palatable foods and affects sensitivity to food rewards in male and female adult rats

Clinical evidence suggests that intrauterine growth restriction (IUGR) can cause persistent changes in the preference for palatable foods. In this study, we compared food preferences, the response to food rewards, and the role of the mesolimbic dopaminergic system in feeding behavior, between IUGR and control rats. Time-mated pregnant Sprague-Dawley rats were randomly allocated to a control group (standard chow ad libitum) or a 50% food restriction (FR) group, which received 50% of the control dams׳ habitual intake. These diets were provided from gestation day 10 to the 21st day of lactation. Within 24h of birth, pups were cross-fostered and divided into four groups: Adlib/Adlib, FR/Adlib, FR/FR, Adlib/FR. Standard chow consumption was compared between all groups. Food preferences, conditioned place preference to a palatable diet, and the levels of tyrosine hydroxylase (TH) phosphorylation and D2 receptors in the nucleus accumbens were analyzed and compared between the two groups of interest: Adlib/Adlib (control) and FR/Adlib (exposed to growth restriction during the fetal period only). IUGR adult rats had a stronger preference for palatable foods, but showed less conditioned place preference to a palatable diet than controls. D2 receptors levels were lower in IUGR rats. At baseline, TH and pTH levels were higher in FR/Adlib than control males. Measurements taken after exposure to sweet foods revealed higher levels of TH and pTH in FR/Adlib than control females. These data showed that IUGR rats exhibited a preference for palatable foods, potentially due to alterations in their mesolimbic reward pathway. Additionally, the changes observed in the mesolimbic dopaminergic system of IUGR rats proved to be sex-specific. This article is part of a Special Issue entitled 1618.

Intrauterine growth restriction modifies the hedonic response to sweet taste in newborn pups – Role of the accumbal μ-opioid receptors

Intrauterine growth restriction (IUGR) is associated with increased preference for palatable foods. The hedonic response to sweet taste, modulated by the nucleus accumbens μ-opioid-receptors, may be involved. We investigated hedonic responses and receptor levels in IUGR and Control animals. From pregnancy day 10, Sprague-Dawley dams received either an ad libitum (Control), or a 50% food restricted (FR) diet. At birth, pups were cross-fostered, and nursed by Adlib fed dams. The hedonic response was evaluated at 1 day after birth and at 90 days of life, by giving sucrose solution or water and analyzing the hedonic facial responses (within 60s). Control pups exposed either to water or sucrose resolved their hedonic responses after 16 and 18s, respectively, while FR hedonic responses to sucrose persisted over 20s. FR pups had deceased phospho-μ-opioid-receptor (p=0.009) and reduced phosphor:total mu opioid receptor ratio compared to controls pups (p=0.003). In adults, there was an interaction between group and solution at the end of the evaluation (p=0.044): Control decreased the response after sucrose solution, FR did not change over time. There were no differences in phosphorylation of μ-opioid-receptor in adults. These results demonstrate IUGR newborn rats exhibit alterations in hedonic response accompanied by a decrease in μ-opioid-receptor phosphorylation, though these alterations do not persist at 3 months of age. Opioid system alterations in early life may contribute to the development of preference for highly palatable foods and contribute to rapid weight gain and obesity in IUGR offspring.