Hypophagia induced by glucocorticoid deficiency is associated with an increased activation of satiety-related responses

Abstract

Uchoa ET, Sabino HA, Ruginsk SG, Antunes-Rodrigues J, Elias LL. Hypophagia induced by glucocorticoid deficiency is associated with an increased activation of satiety-related responses. J Appl Physiol 106: 596 -604, 2009. First published November 20, 2008 doi:10.1152/japplphysiol.90865.2008.-Glucocorticoids have major effects on food intake, demonstrated by the decrease of food intake following adrenalectomy. Satiety signals are relayed to the nucleus of the solitary tract (NTS), which has reciprocal projections with the arcuate nucleus (ARC) and paraventricular nucleus (PVN) of the hypothalamus. We evaluated the effects of glucocorticoids on the activation of hypothalamic and NTS neurons induced by food intake in rats subjected to adrenalectomy (ADX) or sham surgery 7 days before the experiments. One-half of ADX animals received corticosterone (ADXϩB) in the drinking water (B: 25 mg/l). Fos/tyrosine hydroxylase (TH), Fos/corticotrophin-releasing factor (CRF) and Fos immunoreactivity were assessed in the NTS, PVN, and ARC, respectively. Food intake and body weight were reduced in the ADX group compared with sham and ADXϩB groups. Fos and Fos/TH in the NTS, Fos, and Fos/CRF immunoreactive neurons in the PVN and Fos in the ARC were increased after refeeding, with higher number in the ADX group, compared with sham and ADXϩB groups. CCK administration showed no hypophagic effect on ADX group despite a similar increase of Fos/TH immunoreactive neurons in the NTS compared with sham and ADXϩB groups, suggesting that CCK alone cannot further increase the anorexigenic effect induced by glucocorticoid deficiency. The present data indicate that glucocorticoid withdrawal reduced food intake, which was associated with higher activation of ARC, CRF neurons of the PVN, and catecholaminergic neurons of the NTS. In the absence of glucocorticoids, satiety signals elicited during a meal lead to an augmented activation of brain stem and hypothalamic pathways. glucocorticoids; food intake; satiety signals; nucleus of the solitary tract; paraventricular nucleus of the hypothalamus; arcuate nucleus of the hypothalamus GLUCOCORTICOIDS PLAY AN IMPORTANT ROLE in the control of feeding behavior. Increased food intake and body weight gain are associated with glucocorticoid treatment in humans (46). On the other hand, bilateral adrenalectomy (ADX) reduces food intake and body weight gain, and these effects are reversed by glucocorticoid replacement in rats (12). Furthermore, ADX reduces hyperphagia and obesity in different experimental models, whereas glucocorticoid replacement reverses these effects (4,8,52). Hypophagia induced by ADX has been associated with a decrease of mRNA expression of hypothalamic neuropeptide Y (NPY), a potent orexigenic neuropeptide (41). ADX also may reduce food intake through the increase of corticotrophin-releasing factor (CRF) mRNA expression in the paraventricular nucleus (PVN), since CRF is a well-known anorexigenic peptide (1, 2). CRF neurons in the PVN receive projections from neurons of the nucleus of the...

Neuroendocrine control of satiation

“…A2 neurons seem to be activated in every experimental situation in which food intake is inhibited, including normal satiety [359][360][361][362][363][364]. A2 neurons are recruited in a graded manner in rats after eating, such that larger meals activate larger numbers of A2 neurons [365].…”

Novel Aspects of Glucocorticoids Actions on Energy Homeostasis and Hydromineral Balance

“…The food intake and body weight gain are reduced in ADX animals, being these effects reversed by glucocorticoid replacement (Freedman et al, 1985;Uchoa et al, 2009aUchoa et al, , 2009bUchoa et al, , 2010. Furthermore, ADX is effective in diminishing hyperphagia and obesity under diverse experimental conditions (Bruce et al, 1982;Dubuc and Wilden, 1986;Yukimura et al, 1978).…”

“…Recent studies have demonstrated that the hypophagic response induced by ADX is associated with increased activation of satiety-related responses mediated by brainstem and hypothalamic circuits (Uchoa et al, 2009a(Uchoa et al, , 2009b. Accordingly, the activation of NTS neurons, assessed by the increased number of cells expressing the nuclear c-Fos protein, is increased in ADX animals after feeding, indicating that this nucleus may be involved in the increased satiety responses following glucocorticoid deficiency (Uchoa et al, 2009a). Interestingly, the activation of CRF and OT neurons was also enhanced in the PVN of fed ADX rats, indicating that, besides the brainstem, the hypothalamus may be also involved in these satiety-related responses.…”

“…Accordingly, ADX reduces plasma leptin levels in ad libitum rats (Germano et al, 2007;Savontaus et al, 2002), as well as the meal-induced insulin secretion Uchoa et al, 2012), whereas glucocorticoid treatment increases leptin secretion and leptin expression in adipocytes (Jahng et al, 2008;Slieker et al, 1996;Zakrzewska et al, 1999). Furthermore, the sensitivity to insulin and leptin seems to be enhanced after ADX (Chavez et al, 1997;Zakrzewska et al, 1997), although CCK administration did not significantly alter food intake in ADX rats (Uchoa et al, 2009a). Another hormone that arises as a candidate for the modulation by glucocorticoids is ghrelin, although the effects of this hormone on food intake may also be produced independently of glucocorticoid action.…”

Corticotrophin-releasing factor receptor 2 mediates the enhanced activation of satiety-related responses through oxytocin neurons in the paraventricular nucleus of the hypothalamus after adrenalectomy

“…Bilateral adrenalectomy (ADX) induces hypophagia [1][2][3] and is a well-established experimental model to investigate the mechanisms underlying the hypophagic effect observed in the primary adrenal insufficiency in humans [4]. Accordingly, glucocorticoid replacement to adrenalectomized (ADX) animals reverses the reduction of food intake [2][3][4][5].…”