RESUMO
Vasoactive intestinal peptide (VIP) and corticotrophin-releasing factor (CRF) are anorexigenic neuropeptides that act in the hypothalamus to regulate food intake. Intracerebroventricular (ICV) microinjection of VIP promotes increased plasma adrenocorticotrophic hormone (ACTH) and corticosterone, indicating that VIP activates hypothalamic-pituitary-adrenal axis. The aim of this study was to evaluate the interaction between VIP and CRF, by verifying the effects of ICV administration of VIP on the activity of neurons and CRF mRNA expression in paraventricular nucleus of hypothalamus (PVN). In addition, it was evaluated the effects of pretreatment with CRF type 1 receptor (CRFR1) antagonist (Antalarmin, ANT) or CRF type 2 receptor (CRFR2) antagonist (Antisauvagine-30, AS30) on VIP-induced changes on food intake and plasma parameters of male rats. Compared to Saline group, VIP increased not only the number of Fos-related antigens (FRA)-immunoreactive neurons in the PVN but also CRF mRNA levels in this nucleus. Both ANT and AS30 treatment attenuated the inhibition of food intake promoted by VIP, ANT showing a more pronounced effect. Both antagonists also attenuated VIP-induced reduction and enhancement of free fatty acids and corticosterone plasma levels, respectively, and only AS30 was able to attenuate the hyperglycemia. These results suggest that CRF is an important mediador of VIP effects on energy balance, and CRFR1 and CRFR2 are involved in these responses.
Assuntos
Hormônio Liberador da Corticotropina/fisiologia , Transtornos da Alimentação e da Ingestão de Alimentos/sangue , Transtornos da Alimentação e da Ingestão de Alimentos/induzido quimicamente , Peptídeo Intestinal Vasoativo/efeitos adversos , Hormônio Adrenocorticotrópico/sangue , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Corticosterona/sangue , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Ácidos Graxos/sangue , Transtornos da Alimentação e da Ingestão de Alimentos/genética , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Hipotálamo/metabolismo , Masculino , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Ratos , Ratos Wistar , Peptídeo Intestinal Vasoativo/metabolismoRESUMO
Metabolic endotoxemia contributes to low-grade inflammation in obesity, which causes insulin resistance due to the activation of intracellular proinflammatory pathways, such as the c-Jun N-terminal Kinase (JNK) cascade in the hypothalamus and other tissues. However, it remains unclear whether the proinflammatory process precedes insulin resistance or it appears because of the development of obesity. Hypothalamic low-grade inflammation was induced by prolonged lipopolysaccharide (LPS) exposure to investigate if central insulin resistance is induced by an inflammatory stimulus regardless of obesity. Male Wistar rats were treated with single (1 LPS) or repeated injections (6 LPS) of LPS (100 µg/kg, IP) to evaluate the phosphorylation of the insulin receptor substrate-1 (IRS1), Protein kinase B (AKT), and JNK in the hypothalamus. Single LPS increased the expression of pIRS1, pAKT, and pJNK, whereas the repeated LPS treatment failed to recruit pIRS1 and pAKT. The 6 LPS treated rats showed increased total JNK and pJNK. The 6 LPS rats became unresponsive to the hypophagic effect induced by central insulin administration (12 µM/5 µL, ICV). Prolonged exposure to LPS (24 h) impaired the insulin-induced AKT phosphorylation and the translocation of the transcription factor forkhead box protein O1 (FoxO1) from the nucleus to the cytoplasm of the cultured hypothalamic GT1-7 cells. Central administration of the JNK inhibitor (20 µM/5 µL, ICV) restored the ability of insulin to phosphorylate IRS1 and AKT in 6 LPS rats. The present data suggest that an increased JNK activity in the hypothalamus underlies the development of insulin resistance during prolonged exposure to endotoxins. Our study reveals that weight gain is not mandatory for the development of hypothalamic insulin resistance and the blockade of proinflammatory pathways could be useful for restoring the insulin signaling during prolonged low-grade inflammation as seen in obesity.
Assuntos
Peso Corporal , Hipotálamo/metabolismo , Inflamação/etiologia , Inflamação/metabolismo , Resistência à Insulina , Lipopolissacarídeos/efeitos adversos , Animais , Modelos Animais de Doenças , Endotoxemia , Inflamação/patologia , Insulina/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Neurônios/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de SinaisRESUMO
Leptin resistance is induced by the feedback inhibitors tyrosine phosphatase-1B (PTP1B) and decreased Src homology 2 domain-containing tyrosine phosphatase-2 (SHP-2) signaling. To investigate the participation of PTP1B and SHP-2 in LPS-induced leptin resistance, we injected repeated (6-LPS) intraperitoneal LPS doses (100 µg/kg ip) for comparison with a single (1-LPS) treatment and evaluated the expression of SHP-2, PTP1B, p-ERK1/2, and p-STAT3 in the hypothalamus of male Wistar rats. The single LPS treatment increased the expression of p-STAT3 and PTP1B but not SHP-2. The repeated LPS treatment reduced SHP-2, increased PTP1B, and did not change p-STAT3. We observed that the PTP1B expression induced by the endotoxin was highly colocalized with leptin receptor cells in the hypothalamus of LepRb-IRES-Cre-tdTomato reporter mice. The single, but not the repeated, LPS treatment decreased the food intake and body weight. Leptin had no stimulatory effect on the hypophagia, body weight loss, or pSTAT3 expression in 6-LPS rats, indicating leptin unresponsiveness. Notably, the PTP1B inhibitor (3.0 nmol/rat in 5 µl icv) restored the LPS-induced hypophagia in 6-LPS rats and restored the ability of leptin to reduce food intake and body weight as well as to phosphorylate STAT3 in the arcuate, paraventricular, and ventromedial nuclei of the hypothalamus. The present data suggest that an increased PTP1B expression in the hypothalamus underlies the development of leptin resistance during repeated exposure to LPS. Our findings contribute to understanding the mechanisms involved in leptin resistance during low-grade inflammation as seen in obesity.
Assuntos
Resistência a Medicamentos , Inflamação/metabolismo , Leptina/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 1/fisiologia , Animais , Resistência a Medicamentos/efeitos dos fármacos , Resistência a Medicamentos/genética , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Obesidade/genética , Obesidade/metabolismo , Ratos , Ratos Wistar , Receptores para Leptina/genética , Receptores para Leptina/metabolismoRESUMO
Hypophagia induced by inflammation is associated with Janus kinase (JAK)-2/signal transducer and activator of transcription (STAT) 3 signaling pathway, and leptin-mediated hypophagia is also mediated by JAK2-STAT3 pathway. We have previously reported that lipopolysaccharide (LPS) did not reduce food intake in leptin-resistant high-fat diet (HFD) rats but maintained body weight loss. We investigated whether changes in p-STAT3 expression in the hypothalamus and brain stem could account for the desensitization of hypophagia in HFD animals after a low LPS dose (100 µg/kg). Wistar rats fed standard diet (3.95 kcal/g) or HFD (6.3 kcal/g) for 8 wk were assigned into control diet-saline, control diet-LPS, HFD-saline, and HFD-LPS groups. LPS reduced feeding in the control diet but not HFD. This group showed no p-STAT3 expression in the paraventricular nucleus (PVN) and ventromedial hypothalamic nucleus (VMH), but sustained, though lower than control, p-STAT3 in the nucleus of the solitary tract (NTS) and raphe pallidus (RPa). LPS decreased body weight in HFD rats and increased Fos expression in the NTS. LPS increased body temperature, oxygen consumption, and energy expenditure in both control diet and HFD rats, and this response was more pronounced in HFD-LPS group. Brown adipose tissue (BAT) thermogenesis and increased energy expenditure seem to contribute to body weight loss in HFD-LPS. This response might be related with increased brain stem activation. In conclusion, LPS activates STAT3-mediated pathway in the hypothalamus and brain stem, leading to hypophagia, however, LPS effects on food intake, but not body weight loss, are abolished by leptin resistance induced by HFD. The preserved STAT3 phosphorylation in the brain stem suggests that unresponsiveness to LPS on STAT3 activation under HFD might be selective to the hypothalamus.
Assuntos
Dieta Hiperlipídica , Hipotálamo/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Peso Corporal/fisiologia , Gorduras na Dieta/metabolismo , Ingestão de Alimentos/fisiologia , Hipotálamo/metabolismo , Leptina/metabolismo , Masculino , Ratos , Ratos Wistar , Transdução de Sinais/fisiologiaRESUMO
The present work investigated the participation of interscapular brown adipose tissue (IBAT), which is an important site for thermogenesis, in the anti-obesity effects of C75, a synthetic inhibitor of fatty acid synthase (FAS). We report that a single intracerebroventricular (i.c.v.) injection of C75 induced hypophagia and weight loss in fasted male Wistar rats. Furthermore, C75 induced a rapid increase in core body temperature and an increase in heat dissipation. In parallel, C75 stimulated IBAT thermogenesis, which was evidenced by a marked increase in the IBAT temperature that preceded the rise in the core body temperature and an increase in the mRNA levels of uncoupling protein-1. As with C75, an i.c.v. injection of cerulenin, a natural FAS inhibitor, increased the core body and IBAT temperatures. The sympathetic IBAT denervation attenuated all of the thermoregulatory effects of FAS inhibitors as well as the C75 effect on weight loss and hypophagia. C75 induced the expression of Fos in the paraventricular nucleus, preoptic area, dorsomedial nucleus, ventromedial nucleus, and raphé pallidus, all of which support a central role of FAS in regulating IBAT thermogenesis. These data indicate a role for IBAT in the increase in body temperature and hypophagia that is induced by FAS inhibitors and suggest new mechanisms explaining the weight loss induced by these compounds.
Assuntos
4-Butirolactona/análogos & derivados , Tecido Adiposo Marrom/efeitos dos fármacos , Ácido Graxo Sintase Tipo I/antagonistas & inibidores , Termogênese/efeitos dos fármacos , 4-Butirolactona/administração & dosagem , 4-Butirolactona/farmacologia , Tecido Adiposo Marrom/inervação , Tecido Adiposo Marrom/fisiologia , Animais , Ingestão de Alimentos/efeitos dos fármacos , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Wistar , Temperatura Cutânea/efeitos dos fármacos , SimpatectomiaRESUMO
Anorexia is a common clinical manifestation of primary adrenal gland failure. Adrenalectomy (ADX)-induced hypophagia is reversed by oxytocin (OT) receptor antagonist and is associated with increased activation of satiety-related responses in the nucleus of the solitary tract (NTS). This study evaluated OT projections from the paraventricular nucleus of the hypothalamus (PVN) to the NTS after ADX and the effect of pretreatment with intracerebroventricular injection of an OT receptor antagonist ([d(CH2)5,Tyr(Me)(2),Orn(8)]-vasotocin; OVT) on the activation of NTS neurons induced by feeding in adrenalectomized rats. Adrenalectomized animals showed higher OT labelling in the NTS than the sham and the ADX with corticosterone replacement (ADX + B) groups. Adrenalectomized animals exhibited co-localization of the anterograde tracer Phaseolus vulgaris leucoagglutinin and OT in axons in the NTS as well as OT fibres apposing NTS neurons activated by refeeding. After vehicle pretreatment, compared with fasting, refeeding increased the numbers of Fos- and Fos + TH-immunoreactive neurons in the NTS in sham, ADX and ADX + B groups, with a higher number of these immunolabelled neurons in adrenalectomized animals. Compared with fasting conditions, refeeding also increased the activation of NTS neurons in OVT-pretreated sham, ADX and ADX + B groups, but there was no difference among the three experimental groups. These data demonstrate that OT is upregulated in projections to the NTS following ADX and that OT receptor antagonist reverses the greater activation of NTS neurons induced by feeding after ADX. The data indicate that OT pathways to the NTS contribute to higher satiety-related responses and, thus, to reduce meal size in primary adrenal insufficiency.
Assuntos
Doença de Addison/fisiopatologia , Ocitocina/fisiologia , Resposta de Saciedade/efeitos dos fármacos , Núcleo Solitário/fisiologia , Adrenalectomia , Animais , Ingestão de Alimentos/fisiologia , Fito-Hemaglutininas/farmacologia , Ratos Sprague-Dawley , Receptores de Ocitocina/antagonistas & inibidoresRESUMO
UNLABELLED: Ethanol (ETOH) consumption has been associated with endocrine and autonomic changes, including the development of hypertension. However, the sequence of pathophysiological events underlying the emergence of this effect is poorly understood. AIMS: This study aimed to establish a time-course correlation between neuroendocrine and cardiovascular changes contributing to the development of hypertension following ETOH consumption. METHODS: Male adult Wistar rats were subjected to the intake of increasing ETOH concentrations in their drinking water (first week: 5%, second week: 10%, third and fourth weeks: 20% v/v). RESULTS: ETOH consumption decreased plasma and urinary volumes, as well as body weight and fluid intake. Furthermore, plasma osmolality, plasma sodium and urinary osmolality were elevated in the ETOH-treated rats. ETOH intake also induced a progressive increase in the mean arterial pressure (MAP), without affecting heart rate. Initially, this increase in MAP was correlated with increased plasma concentrations of adrenaline and noradrenaline. After the second week of ETOH treatment, plasma catecholamines returned to basal levels, and incremental increases were observed in plasma concentrations of vasopressin (AVP) and angiotensin II (ANG II). Conversely, plasma oxytocin, atrial natriuretic peptide, prolactin and the hypothalamus-pituitary-adrenal axis components were not significantly altered by ETOH. CONCLUSIONS: Taken together, these results suggest that increased sympathetic activity may contribute to the early increase in MAP observed in ETOH-treated rats. However, the maintenance of this effect may be predominantly regulated by the long-term increase in the secretion of other circulating factors, such as AVP and ANG II, the secretion of both hormones being stimulated by the ETOH-induced dehydration.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Hipertensão/induzido quimicamente , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Consumo de Bebidas Alcoólicas/metabolismo , Consumo de Bebidas Alcoólicas/fisiopatologia , Angiotensina II/sangue , Animais , Pressão Sanguínea/efeitos dos fármacos , Catecolaminas/sangue , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Hipertensão/sangue , Hipertensão/fisiopatologia , Masculino , Prolactina/sangue , Ratos , Vasopressinas/sangueRESUMO
Metabolic programming may be induced by reduction or enhancement of litter size, which lead to neonatal over or undernutrition, respectively. Changes in neonatal nutrition can challenge some regulatory processes in adulthood, such as the hypophagic effect of cholecystokinin (CCK). In order to investigate the effects of nutritional programming on the anorexigenic function of CCK in adulthood, pups were raised in small (SL, 3 pups per dam), normal (NL, 10 pups per dam), or large litters (LL, 16 pups per dam), and on postnatal day 60, male rats were treated with vehicle or CCK (10 µg/Kg) for the evaluation of food intake and c-Fos expression in the area postrema (AP), nucleus of solitary tract (NTS), and paraventricular (PVN), arcuate (ARC), ventromedial (VMH), and dorsomedial (DMH) nuclei of the hypothalamus. Overnourished rats showed increased body weight gain that was inversely correlated with neuronal activation of PaPo, VMH, and DMH neurons, whereas undernourished rats had lower body weight gain, inversely correlated with increased neuronal activation of PaPo only. SL rats showed no anorexigenic response and lower neuron activation in the NTS and PVN induced by CCK. LL exhibited preserved hypophagia and neuron activation in the AP, NTS, and PVN in response to CCK. CCK showed no effect in c-Fos immunoreactivity in the ARC, VMH, and DMH in any litter. These results indicate that anorexigenic actions, associated with neuron activation in the NTS and PVN, induced by CCK were impaired by neonatal overnutrition. However, these responses were not disrupted by neonatal undernutrition. Thus, data suggest that an excess or poor supply of nutrients during lactation display divergent effects on programming CCK satiation signaling in male adult rats.
Assuntos
Desnutrição , Hipernutrição , Ratos , Masculino , Animais , Núcleo Hipotalâmico Paraventricular/metabolismo , Colecistocinina/farmacologia , Colecistocinina/metabolismo , Ratos Wistar , Núcleo Solitário/metabolismo , Ratos Sprague-Dawley , Hipotálamo/metabolismo , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Hipernutrição/metabolismo , Peso Corporal , Ingestão de AlimentosRESUMO
Introduction: Lactation overnutrition is a programming agent of energy metabolism, and litter size reduction leads to the early development of obesity, which persists until adulthood. Liver metabolism is disrupted by obesity, and increased levels of circulating glucocorticoids are pointed as a possible mediator for the obesity development, since bilateral adrenalectomy (ADX) can reduce obesity in different models of obesity. Methods: This study aimed to evaluate the effects of glucocorticoids on metabolic changes and liver lipogenesis and insulin pathway induced by lactation overnutrition. For this, on the postnatal day 3 (PND), 3 pups (small litter-SL) or 10 pups (normal litter-NL) were kept with each dam. On PND 60, male Wistar rats underwent bilateral adrenalectomy (ADX) or fictitious surgery (sham), and half of ADX animals received corticosterone (CORT- 25 mg/L) diluted in the drinking fluid. On PND 74, the animals were euthanized by decapitation for trunk blood collection, and liver dissection and storage. Results and Discussion: SL rats presented increased corticosterone, free fatty acids, total and LDL-cholesterol plasma levels, without changes in triglycerides (TG) and HDL-cholesterol. The SL group also showed increased content of liver TG, and expression of fatty acid synthase (FASN), but decreased expression of PI3Kp110 in the liver, compared to NL rats. In the SL group, the ADX decreased plasma levels of corticosterone, FFA, TG and HDL cholesterol, liver TG, and liver expression of FASN, and IRS2, compared to sham animals. In SL animals, CORT treatment increased plasma levels of TG and HDL cholesterol, liver TG, and expression of FASN, IRS1, and IRS2, compared with the ADX group. In summary, the ADX attenuated plasma and liver changes observed after lactation overnutrition, and CORT treatment could reverse most ADX-induced effects. Thus, increased circulating glucocorticoids are likely to play a pivotal role in liver and plasma impairments induced by lactation overnutrition in male rats.
RESUMO
The arcuate nucleus of hypothalamus (ARC) integrates circulating factors that signal energy status. The vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are widely distributed in the periphery and central nervous systems (CNS) and play important roles on energy balance. The present study aimed to investigate the responses of microinjection of VIP and PACAP in the ARC on metabolic changes and food intake. In addition, the activity of neurons in the ARC following intracerebroventricular (ICV) microinjection of these peptides was also evaluated. Microinjection of VIP or PACAP in the ARC decreased fasting-induced hyperphagia and food intake, decreased total lipids, and increased free fatty acids plasma concentrations. VIP microinjection in the ARC induced hyperglycemia and decreased total cholesterol level; and PACAP reduced triglycerides concentration. ICV microinjection of VIP and PACAP enhanced neuronal activation in the ARC, associated with lower fasting-induced hyperphagia and plasma metabolic changes (only VIP). These results suggest that VIP and PACAP play important roles in ARC, inducing hypophagia and peripheral metabolic changes, as hyperglycemia, increased free fatty acids and decreased total lipids plasma levels.
Assuntos
Núcleo Arqueado do Hipotálamo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Peptídeo Intestinal Vasoativo , Animais , Núcleo Arqueado do Hipotálamo/metabolismo , Comportamento Alimentar , Hipotálamo/metabolismo , Lipídeos/sangue , Neurônios/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Peptídeo Intestinal Vasoativo/metabolismo , Peptídeo Intestinal Vasoativo/farmacologiaRESUMO
AIMS: Litter size reduction on the first days of life results in increased body weight and adiposity, with higher levels of circulating glucocorticoids. Obese rodents are more sensitive to the anabolic effects of glucocorticoids and less responsive to glucocorticoids feedback on hypothalamic-pituitary-adrenal (HPA) axis. This study aimed to evaluate effects of the treatment with corticosterone on metabolic responses and HPA axis in adult male rats reared in small litters. MAIN METHODS: From postnatal day (PND) 60 to 88, adult male rats of normal (NL- 10 pups/dam) and small (SL- 3 pups/dam) litters received oral treatment with Corticosterone (CORT-15 mg/L) in the drinking water or no treatment, composing the four experimental groups (NL-water; NL-CORT; SL-water and SL-CORT), for the evaluation of energy homeostasis and HPA axis. KEY FINDINGS: Male rats of SL-water group presented on PND88: glucose intolerance, higher adiposity, plasma triglycerides, free fatty acids, total and low-density lipoprotein (LDL) cholesterol and corticosterone. SL-water animals showed increased mRNA of corticotrophin-releasing hormone (CRH) in the hypothalamic paraventricular nucleus (PVN) and proopiomelanocortin (POMC) in the pituitary, with decreased mRNA expression of PVN mineralocorticoid receptor. NL-CORT animals presented glucose intolerance, increased body weight, food intake, total and LDL cholesterol. Glucocorticoid treatment reduced corticosterone levels and adrenal cortex thickness in NL group, associated with increased mRNA of PVN CRH and pituitary POMC, without effects on SL animals. SIGNIFICANCE: Lactation overnutrition promotes hyperreactivity of HPA axis and reduces the responsiveness to glucocorticoids effects on energy balance and negative feedback of HPA axis in adult male rats.
Assuntos
Intolerância à Glucose , Hipernutrição , Animais , Corticosterona , Hormônio Liberador da Corticotropina/metabolismo , Feminino , Glucocorticoides/farmacologia , Intolerância à Glucose/metabolismo , Homeostase , Sistema Hipotálamo-Hipofisário/metabolismo , Lactação , Masculino , Obesidade/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Pró-Opiomelanocortina/metabolismo , RNA Mensageiro/metabolismo , Ratos , Água/metabolismoRESUMO
Vasoactive intestinal peptide (VIP), a neuromodulator present in the hypothalamus, plays an important role in the regulation of food intake. Paraventricular nucleus of the hypothalamus (PVN) is involved in ingestive responses and regulates the nitric oxide (NO) pathway. The main objectives of this study were to investigate metabolic changes established after different doses and times of VIP microinjection on the PVN, and the effect of VIP microinjection on the PVN on food intake and the role of NO in this control. In anesthetized rats, increased blood plasma glucose and insulin levels were observed following the doses of 40 and 80 ng/g of body weight. At the dose of 40 ng/g, VIP promoted hyperglycemia and hyperinsulinemia 5, 10, and 30 min after microinjection, and increased free fatty acids and total lipids plasma levels after 5 min, and triglycerides after 10 min. In awake animals, once again, VIP administration increased plasmatic levels of glucose, free fatty acids, corticosterone, and insulin 10 min after the microinjection. Moreover, VIP promoted hypophagia in the morning and night periods, and L-arginine (L-Arg) and monosodium glutamate (MSG) or a combination of both attenuated VIP-induced reduction on food intake. In addition, nitrate concentration in the PVN was decreased after VIP microinjection. Our data show that the PVN participates in the anorexigenic and metabolic effects of VIP, and that VIP-induced hypophagia is likely mediated by reduction of NO.
Assuntos
Insulinas , Núcleo Hipotalâmico Paraventricular , Animais , Arginina/metabolismo , Arginina/farmacologia , Glicemia/metabolismo , Corticosterona , Ácidos Graxos não Esterificados/metabolismo , Ácidos Graxos não Esterificados/farmacologia , Insulinas/metabolismo , Insulinas/farmacologia , Neurotransmissores/metabolismo , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Ratos , Glutamato de Sódio/metabolismo , Glutamato de Sódio/farmacologia , Triglicerídeos/metabolismo , Triglicerídeos/farmacologia , Peptídeo Intestinal Vasoativo/metabolismo , Peptídeo Intestinal Vasoativo/farmacologiaRESUMO
OBJECTIVE: To analyze the effects of the ice popsicle on vasopressin, osmolality, thirst intensity, and thirst discomfort. METHOD: This is a quasi-experimental, pre- and post-test study conducted in a laboratory. The sample consisted of nine healthy male volunteers, who received 2% hypertonic saline solution. RESULTS: Popsicle intake did not result in a statistically significant reduction in vasopressin levels (F=0.876 and p=0.428). However, there was a reduction in the hormonal physiological profile of vasopressin from 7.1 pg/ml to 5.8 pg/ml after the first two interventions. Osmolality concentration changed from 270.65 to 286.51 mOsm/kg, with no statistical difference (F=2.207; p=0.09). Ice popsicles significantly reduced thirst intensity (F=10.00; p=0.001) and thirst discomfort (F=10.528; p <0.001). CONCLUSION: There was a reduction in thirst intensity and discomfort after the use of the 20 ml ice popsicle. There was no statistical difference for vasopressin and osmolality. However, there was a reduction in the hormonal physiological profile of vasopressin during 30 minutes of intervention.
Assuntos
Gelo , Sede , Humanos , Masculino , Concentração Osmolar , Solução Salina Hipertônica , VasopressinasRESUMO
This work evaluated the effects of neonatal overfeeding, induced by litter size reduction, on fertility and the noradrenaline-kisspeptin-gonadotrophin releasing hormone (GnRH) pathway in adult female rats. The litter size was adjusted to 3 pups with each mother in the small litters (SL) and 10 pups with each mother in the normal litters (NL). SL females exhibited metabolic changes associated with reproductive dysfunctions, shown by earlier vaginal opening and first estrus, later regular cyclicity onset, and lower and higher occurrences of estrus and diestrus phases, respectively, as well as reduced fertility, estradiol plasma levels, and mRNA expressions of tyrosine hydroxylase in the locus coeruleus, kisspeptin, and GnRH in the preoptic area in adult females in the afternoon of proestrus. These results suggest that neonatal overfeeding in female rats promotes reproductive dysfunctions in adulthood, such as lower estradiol plasma levels associated with impairments in fertility and noradrenaline-kisspeptin-GnRH pathway during positive feedback.
Assuntos
Envelhecimento/fisiologia , Estradiol/sangue , Fertilidade/fisiologia , Hormônio Liberador de Gonadotropina/metabolismo , Kisspeptinas/metabolismo , Norepinefrina/metabolismo , Hipernutrição/sangue , Hipernutrição/metabolismo , Animais , Animais Recém-Nascidos , Glicemia/metabolismo , Tronco Encefálico/patologia , Ciclo Estral , Feminino , Hormônio Liberador de Gonadotropina/genética , Gônadas/patologia , Hipotálamo/patologia , Lipídeos/sangue , Tamanho da Ninhada de Vivíparos , Masculino , Hipófise/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Maturidade Sexual , Aumento de PesoRESUMO
Adrenalectomy-induced hypophagia is associated with increased satiety-related responses, which involve neuronal activation of the nucleus of the solitary tract (NTS). Besides its effects on the pituitary-adrenal axis, corticotrophin-releasing factor (CRF) has been shown to play an important role in feeding behaviour, as it possesses anorexigenic effects. We evaluated feeding-induced CRF mRNA expression in the paraventricular nucleus (PVN) and the effects of pretreatment with CRF(2) receptor antagonist (Antisauvagine-30, AS30) on food intake and activation of NTS neurons in response to feeding in adrenalectomised (ADX) rats. Compared to the sham group, ADX increased CRF mRNA levels in the PVN of fasted animals, which was further augmented by refeeding. AS30 treatment did not affect food intake in the sham and ADX+corticosterone (B) groups; however, it reversed hypophagia in the ADX group. In vehicle-pretreated animals, refeeding increased the number of Fos and Fos/TH-immunoreactive neurons in the NTS in the sham, ADX and ADX+B groups, with the highest number of neurons in the ADX animals. Similarly to its effect on food intake, pretreatment with AS30 in the ADX group also reversed the increased activation of NTS neurons induced by refeeding while having no effect in the sham and ADX+B animals. The present results show that adrenalectomy induces an increase in CRF mRNA expression in the PVN potentiated by feeding and that CRF(2) receptor antagonist abolishes the anorexigenic effect and the increased activation of NTS induced by feeding in the ADX animals. These data indicate that increased activity of PVN CRF neurons modulates brainstem satiety-related responses, contributing to hypophagia after adrenalectomy.
Assuntos
Adrenalectomia , Hormônio Liberador da Corticotropina/fisiologia , Ingestão de Alimentos/genética , Transtornos da Alimentação e da Ingestão de Alimentos/genética , Resposta de Saciedade , Adrenalectomia/reabilitação , Animais , Corticosterona/farmacologia , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/metabolismo , Regulação para Baixo/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Transtornos da Alimentação e da Ingestão de Alimentos/induzido quimicamente , Transtornos da Alimentação e da Ingestão de Alimentos/metabolismo , Expressão Gênica/efeitos dos fármacos , Antagonistas de Hormônios/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/metabolismo , Fragmentos de Peptídeos/farmacologia , Ratos , Ratos Wistar , Receptores de Hormônio Liberador da Corticotropina/antagonistas & inibidores , Resposta de Saciedade/efeitos dos fármacos , Resposta de Saciedade/fisiologiaRESUMO
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 (ADX+B) 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 ADX+B 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 ADX+B 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 ADX+B 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.
Assuntos
Comportamento Animal , Ingestão de Alimentos , Transtornos da Alimentação e da Ingestão de Alimentos/fisiopatologia , Glucocorticoides/deficiência , Hipotálamo/fisiopatologia , Resposta de Saciedade , Núcleo Solitário/fisiopatologia , Adrenalectomia , Animais , Núcleo Arqueado do Hipotálamo/metabolismo , Núcleo Arqueado do Hipotálamo/fisiopatologia , Peso Corporal , Catecolaminas/metabolismo , Colecistocinina/administração & dosagem , Corticosterona/administração & dosagem , Hormônio Liberador da Corticotropina/metabolismo , Modelos Animais de Doenças , Ingestão de Líquidos , Jejum , Transtornos da Alimentação e da Ingestão de Alimentos/metabolismo , Hipotálamo/metabolismo , Masculino , Vias Neurais/metabolismo , Vias Neurais/fisiopatologia , Neurônios/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Núcleo Hipotalâmico Paraventricular/fisiopatologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Wistar , Núcleo Solitário/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Glucocorticoids have major effects on food intake, as demonstrated by the decrease of food intake following adrenalectomy (ADX); however, the mechanisms leading to these effects are not well understood. Oxytocin (OT) has been shown to reduce food intake. We evaluated the effects of glucocorticoids on OT neuron activation and OT mRNA expression in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei induced by feeding. We also evaluated the effect of pretreatment with OT-receptor antagonist ([d(CH2)5,Tyr(Me)2,Orn8]-vasotocin, OVT) on food intake in ADX rats. Fos/OT neurons in the posterior parvocellular subdivision of the PVN were increased after refeeding, with a higher number in the ADX group, compared with sham and ADX+corticosterone (B) groups, with no difference in the medial parvocellular and magnocellular subdivisions of the PVN. ADX increased OT mRNA expression in the PVN both in fasting and refeeding condition, compared with sham and ADX+B groups. In the SON, refeeding increased the number of Fos/OT neurons, with a higher number in the ADX+B group. In fasted condition, OT mRNA expression in the SON was increased in ADX and ADX+B, compared with sham group. Pretreatment with OVT reversed the ADX-induced hypophagia, with no difference between sham and ADX+B animals. The present results show that glucocorticoid withdrawal induces a higher activation of PVN OT neurons in response to feeding, and an increase of OT mRNA expression in the PVN and OT-receptor antagonist reverses the anorexigenic effect induced by ADX. These data indicate that PVN OT neurons might mediate the hypophagic effect induced by adrenalectomy.
Assuntos
Regulação do Apetite/fisiologia , Neurônios/metabolismo , Ocitocina/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Núcleo Supraóptico/metabolismo , Adrenalectomia , Análise de Variância , Animais , Corticosterona/fisiologia , Ingestão de Alimentos/fisiologia , Regulação da Expressão Gênica/fisiologia , Sistema Hipotálamo-Hipofisário/fisiologia , Masculino , Ocitocina/genética , Núcleo Hipotalâmico Paraventricular/citologia , RNA Mensageiro/análise , Ratos , Ratos Wistar , Estatísticas não Paramétricas , Núcleo Supraóptico/citologiaRESUMO
PURPOSE: The aim of this study is to evaluate the effects of adrenalectomy (ADX) and glucocorticoid in the changes induced by intracerebroventricular (ICV) administration of vasoactive intestinal peptide (VIP) on food intake and plasma parameters, as well as VIP receptor subtype 2 (VPAC2) mRNA expression in different hypothalamic nuclei of male rats. METHODS: Male Wistar rats (260-280 g) were subjected to ADX or sham surgery, 7 days before the experiments. Half of ADX animals received corticosterone (ADX + CORT) in the drinking water. Animals with 16 h of fasting received ICV microinjection of VIP or saline (0.9% NaCl). After 15 min: (1) animals were fed, and the amount of food ingested was quantified for 120 min; or (2) animals were euthanized and blood was collected for biochemical measurements. Determination of VPAC2 mRNA levels in LHA, ARC, and PVN was performed from animals with microinjection of saline. RESULTS: VIP treatment promoted the anorexigenic effect, which was not observed in ADX animals. Microinjection of VIP also induced an increase in blood plasma glucose and corticosterone levels, and a reduction in free fatty acid plasma levels, but adrenalectomy abolished these effects. In addition, adrenalectomy reduced mRNA expression of VPAC2 in the lateral hypothalamic area and arcuate nucleus, but not in the paraventricular nucleus. CONCLUSIONS: These results suggest that adrenal glands are required for VIP-induced changes in food intake and plasma parameters, and these responses are associated with reduction in the expression of VPAC2 in the hypothalamus after adrenalectomy.
Assuntos
Adrenalectomia/efeitos adversos , Ingestão de Alimentos/efeitos dos fármacos , Peptídeo Intestinal Vasoativo/farmacologia , Animais , Núcleo Arqueado do Hipotálamo/metabolismo , Glicemia/análise , Corticosterona/sangue , Corticosterona/farmacologia , Ácidos Graxos não Esterificados/sangue , Região Hipotalâmica Lateral/metabolismo , Masculino , Microinjeções , Núcleo Hipotalâmico Paraventricular/metabolismo , Ratos , Ratos Wistar , Receptores Tipo II de Peptídeo Intestinal Vasoativo/metabolismoRESUMO
Adrenalectomy (ADX) induces hypophagia and glucocorticoids counter-regulate the peripheral metabolic effects of insulin. This study evaluated the effects of ADX on ICV (lateral ventricle) injection of insulin-induced changes on food intake, mRNA expression of hypothalamic neuropeptides (insulin receptor (InsR), proopiomelanocortin, cocaine and amphetamine-regulated transcript (Cart), agouti-related protein, neuropeptide Y (Npy) in the arcuate nucleus of the hypothalamus (ARC), corticotrophin-releasing factor in the paraventricular nucleus of the hypothalamus) and hypothalamic protein content of insulin signaling-related molecules (insulin receptor substrate (IRS) 1, protein kinase B (AKT), extracellular-signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK), protein tyrosine phosphatase-1B (PTP1B) and T cell protein tyrosine phosphatase (TCPTP)) Compared with sham animals, ADX increased the hypothalamic content of pJNK/JNK, PTP1B and TCPTP, as well as decreased mRNA expression of InsR, and corticosterone (B) treatment reversed these effects. Insulin central injection enhanced hypothalamic content of pAKT/AKT and Cart mRNA expression, decreased Npy mRNA expression and food intake only in sham rats, without effects in ADX and ADX + B rats. Insulin did not alter the hypothalamic phosphorylation of IRS1 and ERK1/2 in the three experimental groups. These data demonstrate that ADX reduces the expression of InsR and increases insulin counter-regulators in the hypothalamus, as well as ADX abolishes hypophagia, activation of hypothalamic AKT pathway and changes in Cart and Npy mRNA expression in the ARC induced by insulin. Thus, the higher levels of insulin counter-regulatory proteins and lower expression of InsR in the hypothalamus are likely to underlie impaired insulin-induced hypophagia and responses in the hypothalamus after ADX.
Assuntos
Adrenalectomia/métodos , Ingestão de Alimentos/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Insulina/farmacologia , Animais , Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Núcleo Arqueado do Hipotálamo/metabolismo , Corticosterona/farmacologia , Expressão Gênica/efeitos dos fármacos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Hipotálamo/metabolismo , Injeções Intraventriculares , Insulina/administração & dosagem , Masculino , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neuropeptídeo Y/genética , Neuropeptídeo Y/metabolismo , Pró-Opiomelanocortina/genética , Pró-Opiomelanocortina/metabolismo , Ratos Wistar , Receptor de Insulina/genética , Receptor de Insulina/metabolismoRESUMO
AIM: Parkinson's disease (PD) is a progressive neurodegenerative disease that manifests itself clinically after reaching an advanced pathological stage. Besides motor signals, PD patients present cardiovascular and autonomic alterations. Recent data showed that rats induced to Parkinsonism by 6-hydroxydopamine (6-OHDA) administration in the substantia nigra pars compacta (SNpc) showed lower mean arterial pressure (MAP) and heart rate (HR), as reduction in sympathetic modulation. The paraventricular nucleus of the hypothalamus (PVN) is an important site for autonomic and cardiovascular control, and amino acid neurotransmission has a central role. We evaluate PVN amino acid neurotransmission in cardiovascular and autonomic effects of 6-OHDA Parkinsonism. METHODS: Male Wistar rats were submitted to guide cannulas implantation into the PVN. 6-OHDA or sterile saline (sham) was administered bilaterally in the SNpc. After 7 days, cardiovascular recordings in conscious state was performed. RESULTS: Bicuculline promoted an increase in MAP and HR in sham group and exacerbated those effects in 6-OHDA group. NBQX (non-NMDA inhibitor) did not promote changes in sham as in 6-OHDA group. On the other hand, PVN microinjection of LY235959 (NMDA inhibitor) in sham group did not induced cardiovascular alterations, but decreased MAP and HR in 6-OHDA group. Compared to Sham group, 6-OHDA lesion increased the number of neuronal nitric oxide synthase (nNOS)-immunoreactive neurons in the PVN and, nNOS inhibition promoted higher increases in MAP and HR. CONCLUSION: Our data suggest that the decreased baseline blood pressure and heart rate in animals with Parkinsonism may be due to an increased GABAergic tone via nNOS in the PVN.