Adrenalectomy enhances endotoxemia-induced hypophagia: higher activation of corticotrophin-releasing-factor and proopiomelanocortin hypothalamic neurons

Rorato, Rodrigo; Castro, Margaret de; Borges, Beatriz de Carvalho; Benedetti, M.; Germano, Carla Maria Ramos; Antunes‐Rodrigues, José; Elias, Lucila Leico Kagohara

doi:10.1016/j.yhbeh.2008.02.011

Cited by 23 publications

(26 citation statements)

References 51 publications

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“…Our results are in agreement with the work of Rorato et al (15), which showed that ADX induced an increase of POMC mRNA and Fos expression in ␣-MSH-immunoreactive neurons in rats.…”

Section: Discussionsupporting

confidence: 94%

Corticosterone Regulates Synaptic Input Organization of POMC and NPY/AgRP Neurons in Adult Mice

et al. 2010

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Changes in circulating hormones, such as leptin and ghrelin, induce alterations in synaptic input organization and electrophysiological properties of neurons of the arcuate nucleus of the hypothalamus. To assess whether changes in circulating glucocorticoids also alter synaptic arrangement and membrane potential properties, we studied the effect of adrenalectomy (ADX) and corticosterone replacement in mice on the proopiomelanocortin (POMC) and neuropeptide Y (NPY)/ agouti-related protein (AgRP) neurons of the hypothalamic arcuate nucleus. ADX reduced the number of symmetric, putative inhibitory synapses onto POMC neurons and the number of asymmetric, putative excitatory synapses onto NPY/AgRP neurons. Corticosterone replacement in ADX mice to levels similar to sham-operated animals restored the number of synapses onto POMC and NPY/AgRP neurons to that seen in sham-operated controls. The alterations in the synaptic arrangement in ADX mice were not due to their decrease in food intake as evidenced by the synaptic analysis of the pair-fed control animals. In line with the altered synaptic input organization, a depolarization of POMC membrane potential and a hyperpolarization of NPY/AgRP membrane potential were observed in ADX mice compared with their sham-operated controls. All of these changes reverted upon corticosterone replacement. These results reveal that the known orexigenic action of corticosteroids is mediated, at least in part, by synaptic changes and altered excitability of the melanocortin system. (Endocrinology 151: 5395-5402, 2010) T he hypothalamus plays an important role in the regulation of many physiological phenomena, including energy expenditure, food intake, circadian rhythm, sleep, body temperature, blood pressure, and gonadal function (1-4).Within the hypothalamus, neurons located in the arcuate nucleus (ARC) are highly responsive to many peripheral hormones, including leptin, insulin, glucocorticoids, ghrelin, thyroid hormones, and other signals as well (5, 6). These peripheral hormones influence energy homeostasis either by activating or inhibiting the activity of the two antagonistic arcuate neuronal populations: the anorexigenic proopiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript-expressing neurons and the orexigenic agouti-related protein (AgRP) and neuropeptide Y (NPY)-containing neurons (for review, see ref. 5). During food deprivation, which is characterized by low levels of circulating leptin and thyroid hormone and high levels of corticosterone and ghrelin, NPY/AgRP neurons are activated and POMC/cocaine and amphetamine-regulated transcript neurons are inhibited. The intracellular events that occur in these neuronal populations have been the object of intense studies. Recent reports from our and other's laboratories (7-9) have focused on the effect of hormones on synaptic mechanisms believed to play an important role in the regulation of the activity of these neurons.

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“…Our results are in agreement with the work of Rorato et al (15), which showed that ADX induced an increase of POMC mRNA and Fos expression in ␣-MSH-immunoreactive neurons in rats.…”

Section: Discussionsupporting

confidence: 94%

Corticosterone Regulates Synaptic Input Organization of POMC and NPY/AgRP Neurons in Adult Mice

et al. 2010

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“…However, our neuroanatomical data show that the early responses to LPS were not accompanied by detectable changes in c-fos transcription in POMC neurons, in agreement with 2 previ- ous studies in the rat (18,61). Previous studies have also documented that LPS-induced changes in immediate early genes, neuropeptides, and inflammatory genes are typically more profound in the PVH than in the ARC (13,18,38,(62)(63)(64)(65)(66).…”

Section: Role Of the Arc In Inflammatory Anorexiasupporting

confidence: 91%

Lipopolysacharide Rapidly and Completely Suppresses AgRP Neuron-Mediated Food Intake in Male Mice

Liu

Huang

Liu³

et al. 2016

Endocrinology

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Although Agouti-related peptide (AgRP) neurons play a key role in the regulation of food intake, their contribution to the anorexia caused by proinflammatory insults has yet to be identified. Using a combination of neuroanatomical and pharmacogenetics experiments, this study sought to investigate the importance of AgRP neurons and downstream targets in the anorexia caused by the peripheral administration of a moderate dose of lipopolysaccharide (LPS) (100 μg/kg, ip). First, in the C57/Bl6 mouse, we demonstrated that LPS induced c-fos in select AgRP-innervated brain sites involved in feeding but not in any arcuate proopiomelanocortin neurons. Double immunohistochemistry further showed that LPS selectively induced c-Fos in a large subset of melanocortin 4 receptor-expressing neurons in the lateral parabrachial nucleus. Secondly, we used pharmacogenetics to stimulate the activity of AgRP neurons during the course of LPS-induced anorexia. In AgRP-Cre mice expressing the designer receptor hM3Dq-Gq only in AgRP neurons, the administration of the designer drug clozapine-N-oxide (CNO) induced robust food intake. Strikingly, CNO-mediated food intake was rapidly and completely blunted by the coadministration of LPS. Neuroanatomical experiments further indicated that LPS did not interfere with the ability of CNO to stimulate c-Fos in AgRP neurons. In summary, our findings combined together support the view that the stimulation of select AgRP-innervated brain sites and target neurons, rather than the inhibition of AgRP neurons themselves, is likely to contribute to the rapid suppression of food intake observed during acute bacterial endotoxemia.

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“…Free-floating sections were then washed with PB and incubated with biotin-labeled anti-rabbit immunoglobulin (Vector Laboratories, Burlingame, CA; 1:200 dilution in 1.5% normal goat serum-PB), followed by the avidin-biotin-peroxidase complex (Vector; 1:200 dilution in PB), both for 1 h at room temperature. The blue-black labeling of cell nucleus was detected using diaminobenzidine hydrochloride (DAB; Sigma Chemical, St. Louis, MO) intensified with 1% cobalt chloride and 1% nickel ammonium sulfate (33). For double labeling, sections processed for Fos were incubated for 48 h at 4°C with monoclonal anti-tyrosine hydroxylase antibody (anti-TH), raised in mouse (Chemicon; 1:1,000), to identify catecholaminergic neurons, or with rabbit anti-CRF (Bachem; 1: 10,000).…”

Section: Perfusion Tissue Preparation and Immunohistochemistrymentioning

confidence: 99%

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

Uchôa¹,

Sabino²,

Ruginsk³

et al. 2009

Journal of Applied Physiology

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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...

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Adrenalectomy enhances endotoxemia-induced hypophagia: higher activation of corticotrophin-releasing-factor and proopiomelanocortin hypothalamic neurons

Cited by 23 publications

References 51 publications

Corticosterone Regulates Synaptic Input Organization of POMC and NPY/AgRP Neurons in Adult Mice

Corticosterone Regulates Synaptic Input Organization of POMC and NPY/AgRP Neurons in Adult Mice

Lipopolysacharide Rapidly and Completely Suppresses AgRP Neuron-Mediated Food Intake in Male Mice

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

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