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Reconstruction of dorsal medullary injection sites. Black dots or open circles indicate the location of the injector tip. Of the 29 cannula placements, 26 were located in a position within 1 mm anterior to the AP, i.e. twenty six spots (black dots) were checked to lie within the dorsal vagal complex (DVC), and three spots (open circles) were checked to lie outside the DVC. Placements shown were-13.24 mm from bregma (A). The other 3 injection sites were at the level of the AP (B),-13.80 mm from bregma. AP, area postrema; Sol, solitary tract; 4V, the fourth ventricle; NTS, nucleus of the solitary tract; 10N, dorsal motor nuclear of the vagus nerve; 12N, hypoglossal nucleus.
Source publication
Ghrelin, an endogenous ligand for the growth hormone secretagogue (GHS) receptor, stimulates feeding and increases body weight. The primary action site of ghrelin has been reported to be the neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons in the hypothalamic arcuate nucleus (ARC). In addition to the hypothalamus, the caudal brainstem als...
Context in source publication
Context 1
... At the end of the test, all the brains of the rats were stained with pontamine sky blue and sectioned in the coronal plane on a freezing microtome (Kryostat 1720, Leica, Germany) at a thickness of 50 μm to verify the location of the cannula. Only data from the rats whose injection sites were located within the DVC were included in the study (Fig. ...
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Introduction and objective:
The growing epidemic of childhood obesity has forced scientists to search for methods to prevent feeding disorders. Increasing interest in appetite regulating hormones has revealed their influence on energy homeostasis after birth or even in utero.
State of knowledge:
The presence of ghrelin in the stomach of human fo...
The neuronal coordination of metabolic homeostasis requires the integration of hormonal signals with multiple interrelated central neuronal circuits to produce appropriate levels of food intake, energy expenditure and fuel availability. Ghrelin, a peripherally produced peptide hormone, circulates at high concentrations during nutrient scarcity. Ghr...
Ghrelin is a peptide, composed of 28-amino acid residues, with a characteristic modifi cation by n-octanoid acid, covalently linked to the serine-3. Considering a genomic position, the gene of ghrelin in humans is located on chromosome 3p25-26. Major source of ghrelin seems to be the stomach, but other tissues and organs such as: the small intestin...
We report here that the neuronal (pro)renin receptor (PRR), a key component of the brain renin-angiotensin system (RAS), plays a critical role in the central regulation of high-fat-diet (HFD)-induced metabolic pathophysiology. The neuronal PRR is known to mediate formation of the majority of angiotensin (Ang) II-a key bioactive peptide of the RAS-i...
Ghrelin is a stomach-derived peptide hormone with salient roles in the regulation of energy balance and metabolism. Notably, ghrelin is recognized as the most powerful known circulating orexigenic hormone. Here, we systematically investigated the effects of ghrelin on energy homeostasis and found that ghrelin primarily induces a biphasic effect on...
Citations
... Секретируется он в основном в желудочно-кишечном тракте, в меньшей степени -в поджелудочной железе, гипофизе, гонадах и гипоталамусе [26]. Проникая в аркуатные ядра гипоталамуса, он оказывает сильное орексигенное действие через стимуляцию экспрессии нейропептида У и агути-связывающего белка [12,27], и подавление проопиомеланокортиновой нейрональной активности [28]. На секрецию грелина также оказывает влияние вегетативная нервная система особенно парасимпатическая [29]. ...
The present study was designed to measure pre- and postprandial ghrelin secretion in the children presenting with Prader-Willi syndrome (PWS). The clinical, hormonal, and metabolic characteristics of 17 prepubertal children with the genetically verified diagnosis of PWS, 15 patients with exogenous-constitutional obesity, and 10 healthy children are presented. The children suffering PWS were found to exhibit pre- and postprandial hyperghrelinemia.
... Ghrelin is an orexigenic peptide mainly synthesized by the stomach (Kojima et al., 1999, Ariyasu et al., 2001 and regulated by ingestion of nutrients such that, peripheral ghrelin levels rise before a meal and rapidly decrease after food intake (Ariyasu et al., 2001, Cummings et al., 2001. Ghrelin receptors are present on NPY neurons in the ARC (Willesen et al., 1999, Mondal et al., 2005 where ghrelin acts to stimulate NPY production and increase food intake (Kamegai et al., 2001, Guan et al., 2010. ...
... According to Genebank sequences and the literatures [36,37], NPY, ob-R, β-actin primers were designed. Among them, And β-actin acted as the internal reference. ...
The arcuate nucleus (ARC) in the basal of hypothalamus plays an important role in appetite regulation and energy balance. We sought to investigate the central neuroendocrine mechanism of appetite decrease and weight loss under chronic stress by observing the regulatory effects of Xiaoyaosan decoction in the expression of leptin receptor (ob-R) and neuropeptide Y (NPY) in the ARC. Our results showed that bodyweight and food intake of rats in the 21-day stress group increased slower than those of the normal group. Higher contents of Leptin and ob-R were noted in the 21-day stress group compared with control rats, while NPY expression was not statistically different. Xiaoyaosan powder can significantly downregulate the contents of leptin and ob-R in the hypothalamus of stressed rats. These findings suggest that increase of ob-R expression in the ARC is possibly one key central neuroendocrine change for the somatic discomfort. Weight loss and decreased food intake in rats caused by the binding of leptin to ob-R in hypothalamus do not appear to utilize the NPY pathway. This study also suggests that ob-R in the ARC may act as the target of Xiaoyaosan in regulating the symptoms such as appetite decrease and bodyweight loss under chronic stress.
... Ghrelin also has central action following direct synthesis within the hypothalamus (De Vriese and Delporte, 2008;Wren et al., 2001). After its release into the blood stream, ghrelin reaches the Arc by crossing the blood-brain barrier and activates neuropeptide Y and agouti-related peptide-containing neurons (Guan et al., 2010). The stimulation of the Arc, has been shown to increase food intake (Berthoud, 2002) by increasing the number of meals rather than meal size (Chen et al., 2004;Murphy and Bloom, 2006). ...
... Second, mRNA expressions of AgRP in the hypothalamus and plasma concentrations of ghrelin were higher in offspring of dams fed the S diet. Ghrelin and AgRP are orexigenic (17). Ghrelin stimulates feeding through activation of NPY/AgRP in the hypothalamus in rats (17). ...
... Ghrelin and AgRP are orexigenic (17). Ghrelin stimulates feeding through activation of NPY/AgRP in the hypothalamus in rats (17). Furthermore, it may be that differences in amino acid composition of soy protein and casein accounted for the increase in AgRP mRNA expression in the offspring of dams fed the S diet. ...
We hypothesized that protein source in the nutritionally adequate AIN-93G diets fed during gestation, lactation, and weaning influences food intake (FI) regulation in male offspring of Wistar rats. Pregnant rats were fed the recommended casein-based (C) or soy protein-based (S) diet during gestation (experiment 1) or during gestation and lactation (experiment 2). Pups (n = 12 per group) weaned to C or S diets were followed for 9 wk (experiment 1) or 14 wk (experiment 2). At termination, body weight was 5.4% and 9.4% higher, respectively, in offspring of dams fed the S diet. Altered FI regulation was shown by failure of devazepide (a CCK-A receptor blocker) to block FI reduction after protein preloads in offspring of S diet-fed dams, whereas it had a strong effect on offspring of C diet-fed dams (P < 0.005). Similarly, naloxone (an opioid receptor blocker) blocked FI reduction more after casein than after soy protein preloads (P < 0.01). In experiment 2, offspring of dams fed the S diet had higher hypothalamic gene expression of agouti related protein at weaning (P < 0.05), and higher FI was found throughout postweaning (P < 0.0001). FI reduction after protein preloads at week 7 and after glucose preloads at week 13 was greater in offspring of C diet-fed dams (P < 0.05). Plasma insulin at weaning and insulin, ghrelin, and glucagon-like peptide-1 at week 15 were higher in offspring of S diet-fed dams (all P < 0.05). In conclusion, nutritionally complete C and S diets consumed during gestation and lactation differ in their effects on body weight and FI regulation in the offspring. Extending the diet from gestation alone to throughout gestation and lactation exaggerated the adverse effects of the S diet. However, the diet consumed postweaning had little effect on the outcome.
Objectives:
This study aimed to explore the involvement of the ghrelin pathway from the arcuate nucleus (ARC) to the dorsal vagal complex (DVC) and to determine its role in the regulation of glycolipid metabolism.
Methods:
The protein and mRNA expression of ghrelin and growth hormone (GH) secretagogue receptor type 1a (GHSR-1a) were measured using immunohistochemistry and the polymerase chain reaction (PCR) method, respectively. Ghrelin fiber projections arising from the ARC and projecting into the DVC were investigated using retrograde tracing, combined with fluorescence immunohistochemical staining. The effects of electrical stimulation (ES) of the ARC on ghrelin-responsive, glucose-sensitive DVC neurons, glycolipid metabolism, and liver lipid enzymes were determined using electrical physiological method, biochemical analysis, quantitative real-time PCR (qRT-PCR) and Western blot analysis.
Results:
GHSR-1a was expressed in the DVC neurons. Ghrelin fibers originating from the ARC projected into the DVC. ES of the ARC-activated the ghrelin-responsive glucose-excited (GE) and glucose-inhibited (GI) neurons in the DVC. ES of the ARC significantly elevated the serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and glucose levels; it reduced the serum high-density lipoprotein (HDLC) and insulin levels. Moreover, ES of the ARC increased liver acetyl-CoA carboxylase-1 (ACC-1) and decreased carnitine palmitoyltransferase-1 (CPT-1) expression, resulting in lipid accumulation in the liver. All the aforementioned effects were partially blocked by pretreatment with the ghrelin receptor antagonist [D-Lys-3]-GHRP-6 in the DVC and were reduced by vagotomy. ES of the ARC increased agouti-related protein (AgRP)/neuropeptide Y (NPY) expression in the ARC and ghrelin expression in the DVC.
Conclusion:
Ghrelin fiber projections arising from the ARC and projecting into the DVC play a role in the regulation of afferent glucose metabolism and glycolipid metabolism via the ghrelin receptor GHSR-1a in the DVC.
Over the past 30 years, it has been established that hormones produced by the gut, pancreas, and adipose tissue are key players in the control of body weight. These hormones act through a complex neuroendocrine system, including the hypothalamus, to regulate metabolism and energy homeostasis. In obesity, this homeostatic balance is disrupted, either through alterations in the levels of these hormones or through resistance to their actions. Alterations in gut hormone secretion following gastric bypass surgery are likely to underlie the dramatic and persistent loss of weight following this procedure, as well as the observed amelioration in type 2 diabetes mellitus. Medications based on the gut hormone GLP-1 are currently in clinical use to treat type 2 diabetes mellitus and have been shown to produce weight loss. Further therapies for obesity based on other gut hormones are currently in development.
