Central administration of REV-ERBα agonist promotes opposite responses on energy balance in fasted and fed states.

The REV-ERBα receptor has a recognised role in the regulation of the circadian rhythm system. However, recent evidence suggests that it also contributes to energy balance regulation. Both expression and function of REV-ERBα can be influenced by the energy status of the body. Considering the possibility of the involvement of REV-ERBα in the regulation of energy balance, which is critically regulated by the hypothalamus, and based on the impact of intermittent fasting, the present study evaluated the effects of central administration of REV-ERBα agonist on energy balance in rats exposed to 24 hours of fasting or ad lib. feeding conditions. Initially, 24-hour fasted rats received an acute i.c.v. administration of agonist at doses of 1, 5, 10 or 15 µg per rat and feed efficiency was evaluated. Because 10 µg was a sufficient dose to affect feed efficiency, subsequent experiments used this dose to assess effects of agonist on the following parameters: energy expenditure induced by physical activity and locomotor activity, time spent in physical activity over 24 hours, and glucose and insulin tolerance. In fasted rats, the agonist promoted increased food intake and feed efficiency, with a greater body weight gain associated with less time spent in locomotor activity, suggesting a reduction in energy expenditure induced by physical activity. Furthermore, a reduction in glucose tolerance was noted. By contrast, free-fed rats exhibited reduced food intake and feed efficiency with decreased body weight gain along with an increase in locomotor activity and physical activity-dependent energy expenditure. Thus, i.c.v. administration of REV-ERBα agonist regulates energy balance depending on the energy status of the organism; that is, it promotes a positive energy balance in the fasted state and a negative energy balance in the fed state. These results may be useful in understanding the underlying mechanisms of energy balance disorders and intermittent fasting for body weight control.

Peripheral and Central Glucocorticoid Signaling Contributes to Positive Energy Balance in Rats.

The obesity epidemic has been the target of several studies to understand its etiology. The pathophysiological processes that take to obesity generally relate to the rupture of energy balance. This imbalance can result from environmental and/or endogenous events. Among the endogenous events, the hypothalamic-pituitary-adrenal axis, which promotes stress response via glucocorticoid activity, is considered a modulator of energy balance. However, it remains controversial whether the increase in plasma levels of glucocorticoids results in a positive or negative energy balance. Furthermore, there are no studies comparing different routes of administration of glucocorticoids in this context. Here, we investigated the effects of intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of a specific agonist for glucocorticoid receptors on food intake and energy expenditure in rats. Sixty-day old rats were treated with i.p. or i.c.v. dexamethasone. Food intake and satiety were evaluated, as well as locomotor activity in order to determine energy expenditure. Both i.p. and i.c.v. dexamethasone increased food intake and decreased energy expenditure. Moreover, i.c.v. dexamethasone delayed the onset of satiety. Together, these results confirm that central glucocorticoid signaling promotes a positive energy balance and supports the role of the glucocorticoid system as the underlying cause of psychological stress-induced obesity.

Can early protein restriction induce the development of binge eating?

We tested the hypothesis that perinatal undernourishment is a factor for binge eating. At 52 days rats born from dams fed on 17% protein (Control) or 8% protein (Undernourished) were distributed into four groups, two of which continued to be fed ad libitum chow and two were submitted to three consecutive Restricted/Refeeding (R/R) cycles. According to the following schedule: Control Naïve (from mothers fed 17% protein/no restriction phase); Control Restricted (from mothers fed 17% protein/restriction phase); Undernourished Naïve (from mothers fed 8% protein/no restriction phase); and Undernourished Restricted (from mothers fed 8% protein/restriction phase). Each cycle consisted of a restriction phase (in the first four days 40% of the mean daily individual chow intake was offered for consumption), followed by a refeeding phase (4 days of chow ad libitum). After the three cycles, all animals were subjected to a feeding test (chow diet and palatable food ad libitum for 24h). During the feeding test, the Undernourished Restricted demonstrated rebound hyperphagia during 2, 4 and 6h. These results suggest the perinatal undernourishment cannot contribute to a binge eating phenotype.

Perinatal undernutrition stimulates seeking food reward.

Experiments in animals have revealed that perinatal nutritional restriction, which manifests in adulthood, increases food intake and preference for palatable foods. Considering this, we aimed to evaluate the effects of perinatal malnutrition on hedonic control of feeding behavior. In this study, we divided Wistar rats into two groups according to the diet provided to their mothers during pregnancy and lactation: the control group (diet with 17% casein) and low-protein group (diet with 8% casein). We assessed the animals' motivational behavior in adulthood by giving them a stimulus of food reward. We also assessed their neuronal activation triggered by the stimulus of palatable food using FOS protein labeling of neurons activated in the caudate putamen, paraventricular, dorsomedial, ventromedial, and lateral hypothalamic nuclei and amygdala. Evaluation of body weight in malnourished animals showed reduction from the 6th day of life until adulthood. Analysis of feeding behavior revealed that these animals were more motivated by food reward, but they had delays during learning of the task. This finding correlated with the number of c-FOS-immunoreactive neurons, which indicated that malnourished animals had an increase in the number of neurons activated in response to the palatable diet, especially in the amygdala and caudate putamen. The study therefore confirmed our hypothesis that early nutritional insults promote changes in encephalic control mechanisms, especially those related to food intake and search for reward.