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Urocortin 3 (Ucn3) is an anorexigenic neuropeptide with high affinity for the type 2 corticotropin-releasing factor receptor (CRF₂-R). How the expression of hypothalamic Ucn3 is regulated by fasting and refeeding in genetically obese (fa/fa) Zucker rats is not known. Obese Zucker rats develop early hyperphagia associated with low expression of CRF₂-R in the ventromedial hypothalamic nucleus (VMH) in this phenotype. Although lean (Fa/?) Zucker rats have strong basal expression of CRF₂-R in the VMH, and normally consume less food compared to their obese littermates, at the beginning of refeeding, the lean rats ingested almost the same amount of food as the obese animals. The present study was designed to investigate the dynamics of the expression of CRF₂-R and Ucn3 in the brain of lean and obese Zucker rats fed ad libitum, food-deprived for 48 h, or refed for 1 and 24 h. The levels of expression of Ucn3 mRNA were analyzed in the rostral perifornical hypothalamus (rPFH) and dorsal medial amygdala (MeD), and CRF₂-R mRNA in the VMH and lateral septum (LS) using in situ hybridization. The results showed that in the ad libitum-fed state, both phenotypes had comparable levels of expression of rPFH Ucn3, but the obese rats had lower levels of expression of VMH CRF₂-R. Food deprivation decreased hypothalamic expression of Ucn3 and CRF₂-R in lean but not obese rats. One hour of refeeding triggered expression of rPFH Ucn3 but not VMH CRF₂-R in lean rats, and at 24 h of refeeding the levels of hypothalamic expression of Ucn3 and CRF₂-R returned to those seen in the ad libitum-fed state in both phenotypes. In the LS, the levels of expression of CRF₂-R were not affected by feeding and phenotype. In the MeD, the Ucn3 transcript increased by food deprivation in obese but not lean rats. Therefore, the increase of Ucn3 expression in the MeD in obese food-deprived rats may reflect stronger behavioral effects of food deprivation in this phenotype. The hypothalamic expression of Ucn3 and CRF₂)-R was modulated by the feeding states in lean but not obese rats. The low levels of VMH CRF₂-R may limit anorexigenic Ucn3 effects in the obese phenotype. The low VMH CRF₂-R levels at the beginning of refeeding in lean rats may allow them to ingest a considerable amount of food regardless of the rapidly increased expression of rPFH Ucn3 by refeeding in this phenotype. This article is part of a Special Issue entitled 'Central Control of Food Intake'., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Following refeeding, c-fos expression is induced in a particular set of brain regions that include the nucleus of the solitary tract (NTS), parabrachial nucleus (PB), central amygdala (CeA), paraventricular hypothalamic nucleus (PVH), supraoptic nucleus (SON) and the circumventricular organs. Within the PVH, the expression is particularly intense in the magnocellular division of the nucleus and it is as yet not clear how this activation occurs. The respective contribution of the vagus afferents and lamina terminalis, which conveys signals entering the brain through the forebrain circumventricular organs, has been investigated in rats subjected to a unilateral cervical vagotomy (UCV) or a unilateral lesion of the fibres running within the lamina terminalis (ULT) and projecting to the neuroendocrine hypothalamus. UCV significantly decreased postprandial c-fos expression in the NTS, PB, CeA and parvocellular division of the PVH. In contrast, ULT impaired postprandial activation of the magnocellular neurons in the PVH and SON. The present study also characterized the types of neurons activated in the PVH and SON during refeeding. In the magnocellular regions, arginine-vasopressin (AVP) neurons were activated upon refeeding whereas there was no apparent induction of Fos expression in oxytocin cells. In the parvocellular PVH, postprandial Fos was induced only in 30% of the corticotrophin-releasing factor (CRF) and AVP neurons. The results of the present study suggest that the postprandial activation of the brain requires the integrity of both the vagal- and lamina terminalis-associated pathways.

Eating disorders are frequently triggered by stress and are more prevalent in women than men. First signs often appear during early adolescence, but the biological basis for the sex-specific differences is unknown. Central administration of native relaxin-3 (RLN3) peptide or chimeric/truncated analogues produces differential effects on food intake and HPA axis activity in adult male and female rats, but the precise role of endogenous RLN3 signalling in metabolic and neuroendocrine control is unclear. Therefore, we examined the effects of microRNA-induced depletion (knock-down) of RLN3 mRNA/(peptide) production in neurons of the brainstem nucleus incertus (NI) in female rats on a range of physiological, behavioural and neurochemical indices, including food intake, body weight, anxiety, plasma corticosterone, mRNA levels of key neuropeptides in the paraventricular nucleus of hypothalamus (PVN) and limbic neural activity patterns (reflected by c-fos mRNA). Validated depletion of RLN3 in NI neurons of female rats (n = 8) produced a small, sustained (~ 2%) decrease in body weight, an imbalance in food intake and an increase in anxiety-like behaviour in the large open field, but not in the elevated plus-maze or light/dark box. Furthermore, NI RLN3 depletion disrupted corticosterone regulation, increased oxytocin and arginine-vasopressin, but not corticotropin-releasing factor, mRNA, in PVN, and decreased basal levels of c-fos mRNA in parvocellular and magnocellular PVN, bed nucleus of stria terminalis and the lateral hypothalamic area, brain regions involved in stress and feeding. These findings support a role for NI RLN3 neurons in fine-tuning stress and neuroendocrine responses and food intake regulation in female rats. [ABSTRACT FROM AUTHOR]

The anterior hypothalamic area (AHA) is an important integrative relay structure for a variety of autonomic, endocrine, and behavioral responses including feeding behavior and response to stress. However, changes in the activity of the AHA neurons during stress and feeding in freely moving rats are not clear. The present study investigated the firing rate and burst activity of neurons in the central nucleus of the AHA (cAHA) during sucrose intake in non-stressful conditions and after acute stress in freely behaving rats. Rats were implanted with micro-electrodes into the cAHA, and extracellular multi-unit activity was recorded during 1-h access to 10% sucrose in non-stressful conditions or after acute foot shock stress. Acute stress significantly reduced sucrose intake, total sucrose lick number, and lick frequency in licking clusters, and increased inter-lick intervals. At the cluster start (CS) of sucrose licking, the cAHA neurons increased (CS-excited, 20% of the recorded neurons), decreased (CS-inhibited, 42% of the neurons) or did not change (CS-nonresponsive, 38% of the neurons) their firing rate. Stress resulted in a significant increase in the firing rate of the CS-inhibited neurons by decreasing inter-spike intervals within the burst firing of these neurons. This increase in the stress-induced firing rate of the CS-inhibited neurons was accompanied by a disruption of the correlation between the firing rate of CS-inhibited and CS-nonresponsive neurons that was observed in non-stressful conditions. Stress did not affect the firing rate of the CS-excited and CS-nonresponsive neurons. However, stress changed the pattern of burst firing of the CS-excited and CS-nonresponsive neurons by decreasing and increasing the burst number in the CS-excited and CS-nonresponsive neurons, respectively. These results suggest that the cAHA neurons integrate the signals related to stress and intake of palatable food and play a role in the stress- and eating-related circuitry. [ABSTRACT FROM AUTHOR]

The role played by the endocannabinoid system in the regulation of energy balance is currently generating a great amount of interest among several groups of investigators. This interest in large part comes from the urgent need to develop anti-obesity and anti-cachexia drugs around target systems (such as the endocannabinoid system), which appears to be genuinely involved in energy balance regulation. When activated, the endocannabinoid system favors energy deposition through increasing energy intake and reducing energy expenditure. This system is activated in obesity and following food deprivation, which further supports its authentic function in energy balance regulation. The cannabinoid receptor type 1 (CB1), one of the two identified cannabinoid receptors, is expressed in energy-balance brain structures that are also able to readily produce or inactivate N-arachidonoyl ethanolamine (anandamide) and 2-arachidonoylglycerol (2AG), the most abundantly formed and released endocannabinoids. The brain action of endocannabinoid system on energy balance seems crucial and needs to be delineated in the context of the homeostatic and hedonic controls of food intake and energy expenditure. These controls require the coordinated interaction of the hypothalamus, brainstem and limbic system and it appears imperative to unravel those interplays. It is also critical to investigate the metabolic endocannabinoid system while considering the panoply of functions that the endocannabinoid system fulfills in the brain and other tissues. This article aims at reviewing the potential mechanisms whereby the brain endocannabinoid system influences the regulation energy balance. [Copyright &y& Elsevier]