scholarly journals Neuromedin S Is a Novel Anorexigenic Hormone

Endocrinology ◽  
2005 ◽  
Vol 146 (10) ◽  
pp. 4217-4223 ◽  
Author(s):  
Takanori Ida ◽  
Kenji Mori ◽  
Mikiya Miyazato ◽  
Yutaka Egi ◽  
Shinsuke Abe ◽  
...  

A novel 36-amino acid neuropeptide, neuromedin S (NMS), has recently been identified in rat brain and has been shown to be an endogenous ligand for two orphan G protein-coupled receptors, FM-3/GPR66 and FM-4/TGR-1. These receptors have been identified as neuromedin U (NMU) receptor type 1 and type 2, respectively. In this study, the physiological role of the novel peptide, NMS, on feeding regulation was investigated. Intracerebroventricular (icv) injection of NMS decreased 12-h food intake during the dark period in rats. This anorexigenic effect was more potent and persistent than that observed with the same dose of NMU. Neuropeptide Y, ghrelin, and agouti-related protein-induced food intake was counteracted by coadministration of NMS. Icv administration of NMS increased proopiomelanocortin mRNA expression in the arcuate nucleus (Arc) and CRH mRNA in the paraventricular nucleus (PVN). Pretreatment with SHU9119 (antagonist for α-MSH) and α-helical corticotropin-releasing factor-(9–41) (antagonist for CRH) attenuated NMS-induced suppression of 24-h food intake. After icv injection of NMS, Fos-immunoreactive cells were detected in both the PVN and Arc. When neuronal multiple unit activity was recorded in the PVN before and after icv injection of NMS, a significant increase in firing rate was observed 5 min after administration, and this increase continued for 100 min. These results suggest that the novel peptide, NMS, may be a potent anorexigenic hormone in the hypothalamus, and that expression of proopiomelanocortin mRNA in the Arc and CRH mRNA in the PVN may be involved in NMS action on feeding.

2015 ◽  
Vol 65 (1) ◽  
pp. 45-56 ◽  
Author(s):  
Lin Zhang ◽  
Fang Yang ◽  
Jinhong Cai ◽  
Chunmei Huang ◽  
Zhengkun Wang ◽  
...  

The hypothalamus and leptin play a key role in the regulation of food intake. The present study investigated the effects of 4 weeks of short- or long-photoperiod on serum leptin levels and food intake in relation to mRNA expression levels of neuropeptide Y, agouti-related protein, pro-opiomelanocortin, and cocaine- and amphetamine-regulated transcript in the hypothalamus of Chevrier’s field mouse (Apodemus chevrieri). There was a significant difference in body fat mass, food intake and neuropeptide Y mRNA expression between the two groups, but serum leptin level, agouti-related protein, pro-opiomelanocortin, and cocaine- and amphetamine-regulated transcript mRNA expression in the hypothalamus were not difference between the two groups. The elevation of neuropeptide Y mRNA regulated neuropeptides in the hypothalamus suggests a physiological role of neuroendocrine factors in food intake during the different photoperiod. We conclude that leptin may be involved in energy balance and body mass regulation.


2021 ◽  
Vol 14 (4) ◽  
pp. 293
Author(s):  
Luca Botticelli ◽  
Emanuela Micioni Di Bonaventura ◽  
Massimo Ubaldi ◽  
Roberto Ciccocioppo ◽  
Carlo Cifani ◽  
...  

The Neuropeptide S (NPS), a 20 amino acids peptide, is recognized as the endogenous ligand of a previously orphan G protein-coupled receptor, now termed NPS receptor (NPSR). The limited distribution of the NPS-expressing neurons in few regions of the brainstem is in contrast with the extensive expression of NPSR in the rodent central nervous system, suggesting the involvement of this receptor in several brain functions. In particular, NPS promotes locomotor activity, behavioral arousal, wakefulness, and unexpectedly, at the same time, it exerts anxiolytic-like properties. Intriguingly, the NPS system is implicated in the rewarding properties of drugs of abuse and in the regulation of food intake. Here, we focus on the anorexigenic effect of NPS, centrally injected in different brain areas, in both sated and fasted animals, fed with standard or palatable food, and, in addition, on its influence in the gastrointestinal tract. Further investigations, regarding the role of the NPS/NPSR system and its potential interaction with other neurotransmitters could be useful to understand the mechanisms underlying its action and to develop novel pharmacological tools for the treatment of aberrant feeding patterns and obesity.


2018 ◽  
Vol 107 (1) ◽  
pp. 91-104 ◽  
Author(s):  
Yuko Maejima ◽  
Shoko Yokota ◽  
Katsuhiko Nishimori ◽  
Kenju Shimomura

Oxytocin was discovered in 1906 as a peptide that promotes delivery and milk ejection; however, its additional physiological functions were determined 100 years later. Many recent articles have reported newly discovered effects of oxytocin on social communication, bonding, reward-related behavior, adipose tissue, and muscle and food intake regulation. Because oxytocin neurons project to various regions in the brain that contribute to both feeding reward (hedonic feeding) and the regulation of energy balance (homeostatic feeding), the mechanisms of oxytocin on food intake regulation are complicated and largely unknown. Oxytocin neurons in the paraventricular nucleus (PVN) receive neural projections from the arcuate nucleus (ARC), which is an important center for feeding regulation. On the other hand, these neurons in the PVN and supraoptic nucleus project to the ARC. PVN oxytocin neurons also project to the brain stem and the reward-related limbic system. In addition to this, oxytocin induces lipolysis and decreases fat mass. However, these effects in feeding and adipose tissue are known to be dependent on body weight (BW). Oxytocin treatment is more effective in food intake regulation and fat mass decline for individuals with leptin resistance and higher BW, but is known to be less effective in individuals with normal BW. In this review, we present in detail the recent findings on the physiological role of oxytocin in feeding regulation and the anorexigenic neural pathway of oxytocin neurons, as well as the advantage of oxytocin usage for anti-obesity treatment.


1991 ◽  
Vol 261 (3) ◽  
pp. R522-R530 ◽  
Author(s):  
H. A. Maier ◽  
D. D. Feist

To assess factors controlling seasonal thermoregulatory and reproductive changes, collared lemmings (Dicrostonyx groenlandicus) were exposed for 16 wk to long day (LD, 22 h light: 2 h dark) and warm (15 +/- 3 degrees C), LD and cold (1 +/- 0.5 degrees C), short day (SD, 4 h light: 20 h dark) and warm, SD and cold or acclimatized to outdoor winter conditions (OUT). Hair length and color, body mass, and food intake were monitored weekly. Resting metabolic rates (RMR) and nonshivering thermogenesis (NST) were estimated several times by measuring oxygen consumption before and after norepinephrine injections. Body composition and reproductive condition were determined at the end of the experiment. SD and OUT groups had a 15.8% lower (P less than 0.01) RMR at 7 degrees C than the LD groups. Lower thermal conductance in SD and OUT animals appears due to molt to white winter pelage, which occurred by week 3 in SD but not in LD groups. Neither SD, cold, nor OUT altered NST or reproductive morphology. SD-exposed lemmings showed 19.2% greater growth than those in LD, resulting primarily from a 29.2 and 15.0% increase in lean and ash components, respectively. Cold exposure increased food intake by 34.7%. Results suggest that the pineal gland, which mediates SD effects, may influence molt and growth but not NST or reproductive morphology.


1993 ◽  
Vol 265 (1) ◽  
pp. H146-H151 ◽  
Author(s):  
R. L. Hester ◽  
A. Eraslan ◽  
Y. Saito

This study was designed to determine the physiological role of endothelium-dependent nitric oxide (EDNO) in the control of arteriolar diameter during rest and muscle stimulation. Diameters of first-, second-, and third-order arterioles in the superfused hamster cremaster muscle were measured before and throughout 1 min of field stimulation before and after inhibition of EDNO release. ENDO inhibition by intravenous N omega-nitro-L-arginine methyl ester (L-NAME) significantly attenuated the arteriolar vasodilation in response to 1 microM acetylcholine. First-order arterioles averaged 65 +/- 5 microns at rest and dilated to 86 +/- 6 microns during muscle stimulation (n = 9), second-order arterioles averaged 45 +/- 6 microns and dilated to 72 +/- 3 microns during muscle stimulation (n = 6), with third-order arterioles averaging 29 +/- 2 microns, and dilating to 53 +/- 3 microns during muscle stimulation (n = 7). EDNO inhibition significantly decreased both the resting diameter of first-order arterioles (57 +/- 4 microns) and functional dilation (68 +/- 3 microns; P <0.05). EDNO inhibition had no effect on the resting diameter of second-order arterioles (45 +/- 5 microns) yet significantly attenuated the functional dilation (64 +/- 4 microns; P < 0.05). EDNO inhibition had no effect on either the resting diameter of third-order arterioles (30 +/- 2 microns) or the functional dilation (49 +/- 2 microns).(ABSTRACT TRUNCATED AT 250 WORDS)


2006 ◽  
Vol 191 (1) ◽  
pp. 197-205 ◽  
Author(s):  
Takaharu Maruyama ◽  
Kenichi Tanaka ◽  
Jun Suzuki ◽  
Hiroyuki Miyoshi ◽  
Naomoto Harada ◽  
...  

G protein-coupled bile acid receptor 1 (Gpbar1/M-Bar) is a novel G protein-coupled receptor for bile acid. Tissue distribution and cell-type specificity of Gpbar1 mRNA suggest a potential role for the receptor in the endocrine system; however, the precise physiological role of Gpbar1 still remains to be elucidated. To investigate the role of Gpbar1 in vivo, the Gpbar1 gene was disrupted in mice. In homozygous mice, total bile acid pool size was significantly decreased by 21–25% compared with that of the wild-type mice, suggesting that Gpbar1 contributes to bile acid homeostasis. In order to assess the impact of Gpbar1 deficiency in bile acid homeostasis more precisely, Gpbar1 homozygous mice were fed a high-fat diet for 2 months. As a result, female Gpbar1 homozygous mice showed significant fat accumulation with body weight gain compared with that of the wild-type mice. These findings were also observed in heterozygous mice to the same extent. Although the precise mechanism for fat accumulation in female Gpbar1 homozygous mice remains to be addressed, these data indicate that Gpbar1 is a potential new player in energy homeostasis. Thus, Gpbar1-deficient mice are useful in elucidating new physiological roles for Gpbar1.


2015 ◽  
Vol 309 (5) ◽  
pp. R561-R575 ◽  
Author(s):  
Tsutomu Sasaki ◽  
Yoshihiro Kinoshita ◽  
Sho Matsui ◽  
Shigeru Kakuta ◽  
Hiromi Yokota-Hashimoto ◽  
...  

d-Serine is abundant in the forebrain and physiologically important for modulating excitatory glutamatergic neurotransmission as a coagonist of synaptic N-methyl-d-aspartate (NMDA) receptor. NMDA signaling has been implicated in the control of food intake. However, the role of d-serine on appetite regulation is unknown. To clarify the effects of d-serine on appetite, we investigated the effect of oral d-serine ingestion on food intake in three different feeding paradigms (one-food access, two-food choice, and refeeding after 24-h fasting) using three different strains of male mice (C57Bl/6J, BKS, and ICR). The effect of d-serine was also tested in leptin signaling-deficient db/ db mice and sensory-deafferented (capsaicin-treated) mice. The expression of orexigenic neuropeptides [neuropeptide Y ( Npy) and agouti-related protein ( Agrp)] in the hypothalamus was compared in fast/refed experiments. Conditioned taste aversion for high-fat diet (HFD) was tested in the d-serine-treated mice. Under the one-food-access paradigm, some of the d-serine-treated mice showed starvation, but not when fed normal chow. HFD feeding with d-serine ingestion did not cause aversion. Under the two-food-choice paradigm, d-serine suppressed the intake of high-preference food but not normal chow. d-Serine also effectively suppressed HFD intake but not normal chow in db/ db mice and sensory-deafferented mice. In addition, d-serine suppressed normal chow intake after 24-h fasting despite higher orexigenic gene expression in the hypothalamus. d-Serine failed to suppress HFD intake in the presence of L-701,324, the selective and full antagonist at the glycine-binding site of the NMDA receptor. Therefore, d-serine suppresses the intake of high-preference food through coagonism toward NMDA receptors.


Endocrinology ◽  
2011 ◽  
Vol 152 (9) ◽  
pp. 3492-3503 ◽  
Author(s):  
Laurence Bodineau ◽  
Christopher Taveau ◽  
Hong-Hanh Lê Quan Sang ◽  
Guillaume Osterstock ◽  
Isabelle Queguiner ◽  
...  

Apelin is a bioactive peptide identified as the endogenous ligand of the human orphan G protein-coupled receptor APJ in 1998. The present data show that apelin modulates the activity of magnocellular and parvocellular oxytocin (OXY) neurons in the lactating rat. A combination of in situ hybridization and immunohistochemistry demonstrated the presence of apelin receptor mRNA in hypothalamic OXY neurons. Double immunofluorescence labeling then revealed the colocalization of apelin with OXY in about 20% of the hypothalamic OXY-positive neurons. Intracerebroventricular apelin administration inhibited the activity of magnocellular and parvocellular OXY neurons, as shown by measuring the c-fos expression in OXY neurons or by direct electrophysiological measurements of the electrical activity of these neurons. This effect was correlated with a decrease in the amount of milk ejected. Thus, apelin inhibits the activity of OXY neurons through a direct action on apelin receptors expressed by these neurons in an autocrine and paracrine manner. In conclusion, these findings highlight the inhibitory role of apelin as an autocrine/paracrine peptide acting on OXY neurons during breastfeeding.


2010 ◽  
Vol 433 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Raphael Rozenfeld ◽  
Lakshmi A. Devi

The critical involvement of GPCRs (G-protein-coupled receptors) in nearly all physiological processes, and the presence of these receptors at the interface between the extracellular and the intracellular milieu, has positioned these receptors as pivotal therapeutic targets. Although a large number of drugs targeting GPCRs are currently available, significant efforts have been directed towards understanding receptor properties, with the goal of identifying and designing improved receptor ligands. Recent advances in GPCR pharmacology have demonstrated that different ligands binding to the same receptor can activate discrete sets of downstream effectors, a phenomenon known as ‘ligand-directed signal specificity’, which is currently being explored for drug development due to its potential therapeutic advantage. Emerging studies suggest that GPCR responses can also be modulated by contextual factors, such as interactions with other GPCRs. Association between different GPCR types leads to the formation of complexes, or GPCR heteromers, with distinct and unique signalling properties. Some of these heteromers activate discrete sets of signalling effectors upon activation by the same ligand, a phenomenon termed ‘heteromer-directed signalling specificity’. This has been shown to be involved in the physiological role of receptors and, in some cases, in disease-specific dysregulation of a receptor effect. Hence targeting GPCR heteromers constitutes an emerging strategy to select receptor-specific responses and is likely to be useful in achieving specific beneficial therapeutic effects.


1998 ◽  
Vol 274 (5) ◽  
pp. R1500-R1504 ◽  
Author(s):  
A. Ishihara ◽  
T. Tanaka ◽  
A. Kanatani ◽  
T. Fukami ◽  
M. Ihara ◽  
...  

Neuropeptide Y (NPY) is one of the most potent orexigenic substances known. 1229U91 was found to be a potent and selective NPY antagonist. To elucidate a physiological role of NPY in hyperphagia in obese animals, we studied the effect of 1229U91 on spontaneous food intake in obese and lean Zucker rats. The food intake of Zucker rats was suppressed by intracerebroventricular administration of 1229U91 more potently in obese than in lean animals without abnormal behavior (31.7 and 67.3% inhibition at doses of 10 and 30 μg, respectively, in Zucker fatty rats and 22.2% inhibition at 30 μg in lean rats). This compound markedly suppressed NPY-induced food intake at 30 μg but did not affect galanin-induced food intake, suggesting that the feeding suppression seen in Zucker fatty and lean rats is pharmacologically and behaviorally specific. These results suggest that NPY is involved in feeding behavior in Zucker fatty rats and that NPY contributes to feeding to a greater degree in Zucker fatty than in lean rats. The hyperphagia in Zucker fatty rats may be due to the abnormal overactivation of the NPYergic system.


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