scholarly journals Central Relaxin-3 Administration Causes Hyperphagia in Male Wistar Rats

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3295-3300 ◽  
Author(s):  
B. M. C. McGowan ◽  
S. A. Stanley ◽  
K. L. Smith ◽  
N. E. White ◽  
M. M. Connolly ◽  
...  

Abstract Relaxin-3 (INSL-7) is a recently discovered member of the insulin superfamily. Relaxin-3 mRNA is expressed in the nucleus incertus of the brainstem, which has projections to the hypothalamus. Relaxin-3 binds with high affinity to the LGR7 receptor and to the previously orphan G protein-coupled receptor GPCR135. GPCR135 mRNA is expressed predominantly in the central nervous system, particularly in the paraventricular nucleus (PVN). The presence of relaxin-3 and these receptors in the PVN led us to investigate the effect of central administration of relaxin-3 on food intake in male Wistar rats. The receptor involved in mediating these effects was also investigated. Intracerebroventricular injections of human relaxin-3 (H3) to satiated rats significantly increased food intake 1 h post administration in the early light phase [0.96 ± 0.16 g (vehicle) vs. 1.81 ± 0.21 g (180 pmol H3), P < 0.05] and the early dark phase [2.95 ± 0.45 g (vehicle) vs. 4.39 ± 0.39 g (180 pmol H3), P < 0.05]. Intra-PVN H3 administration significantly increased 1-h food intake in satiated rats in the early light phase [0.34 ± 0.16 g (vehicle) vs. 1.23 ± 0.30 g (18 pmol H3), P < 0.05] and the early dark phase [4.43 ± 0.32 g (vehicle) vs. 6.57 ± 0.42 g (18 pmol H3), P < 0.05]. Feeding behavior increased after intra-PVN H3. Equimolar doses of human relaxin-2, which binds the LGR7 receptor but not GPCR135, did not increase feeding. Hypothalamic neuropeptide Y, proopiomelanocortin, or agouti-related peptide mRNA expression did not change after acute intracerebroventricular H3. These results suggest a novel role for relaxin-3 in appetite regulation.

1989 ◽  
Vol 67 (5) ◽  
pp. 2154-2157 ◽  
Author(s):  
O. Shido ◽  
Y. Yoneda ◽  
T. Nagasaka

Male Wistar rats, initially maintained at an ambient temperature (Ta) of 23.8 degrees C, were subjected to one of seven different heat acclimation schedules under a 12:12-h light-dark cycle (lights on at 0600 h). Two groups of rats were exposed to Ta of 32.4 degrees C all day for 5 (HC5) or 10 (HC10) days. The other four groups were exposed to Ta of 32.8 degrees C for 5 h/day during the last half of the dark phase for 5 (NI5) or 10 (NI10) consecutive days or during the last half of the light phase for 5 (DI5) or 10 (DI10) consecutive days. Control rats (C) were kept at 23.8 degrees C throughout the experiment. Hypothalamic temperature (Thy) was measured every 5 min with a chronically implanted thermocouple from 1 day before the beginning to 2 days after the end of the heat acclimation periods. During the heat acclimation periods, daily mean Thy rose significantly in HC5 and HC10 rats but decreased significantly in NI5 and NI10 rats. Daily mean Thy did not change in C, DI5, and DI10 rats. Thy in HC10 rats sharply decreased at the end of the heat acclimation periods and remained at low levels for approximately 3 h. On the 2nd postacclimation day, however, mean Thy returned and remained at a significantly higher level. In NI10 rats, the mean Thy in the postacclimation period was significantly lower than the preacclimation values. No such changes in mean Thy were observed in DI10 rats. Five-days of heat exposure had little effect on the postacclimation Thy.(ABSTRACT TRUNCATED AT 250 WORDS)


2013 ◽  
pp. 1-1
Author(s):  
Michael Patterson ◽  
John Tadross ◽  
Keisuke Suzuki ◽  
Kylie Beale ◽  
Charoltte Boughton ◽  
...  

2019 ◽  
Vol 20 (10) ◽  
pp. 2452 ◽  
Author(s):  
Martha López-Canul ◽  
Seung Hyun Min ◽  
Luca Posa ◽  
Danilo De Gregorio ◽  
Annalida Bedini ◽  
...  

Melatonin (MLT) is a neurohormone that regulates many physiological functions including sleep, pain, thermoregulation, and circadian rhythms. MLT acts mainly through two G-protein-coupled receptors named MT1 and MT2, but also through an MLT type-3 receptor (MT3). However, the role of MLT receptor subtypes in thermoregulation is still unknown. We have thus investigated the effects of selective and non-selective MLT receptor agonists/antagonists on body temperature (Tb) in rats across the 12/12-h light–dark cycle. Rectal temperature was measured every 15 min from 4:00 a.m. to 9:30 a.m. and from 4:00 p.m. to 9:30 p.m., following subcutaneous injection of each compound at either 5:00 a.m. or 5:00 p.m. MLT (40 mg/kg) had no effect when injected at 5 a.m., whereas it decreased Tb during the light phase only when injected at 5:00 p.m. This effect was blocked by the selective MT2 receptor antagonist 4P-PDOT and the non-selective MT1/MT2 receptor antagonist, luzindole, but not by the α1/MT3 receptors antagonist prazosin. However, unlike MLT, neither the selective MT1 receptor partial agonist UCM871 (14 mg/kg) nor the selective MT2 partial agonist UCM924 (40 mg/kg) altered Tb during the light phase. In contrast, UCM871 injected at 5:00 p.m. increased Tb at the beginning of the dark phase, whereas UCM924 injected at 5:00 a.m. decreased Tb at the end of the dark phase. These effects were blocked by luzindole and 4P-PDOT, respectively. The MT3 receptor agonist GR135531 (10 mg/kg) did not affect Tb. These data suggest that the simultaneous activation of both MT1 and MT2 receptors is necessary to regulate Tb during the light phase, whereas in a complex but yet unknown manner, they regulate Tb differently during the dark phase. Overall, MT1 and MT2 receptors display complementary but also distinct roles in modulating circadian fluctuations of Tb.


2019 ◽  
Vol 4 (4) ◽  
pp. 137-142
Author(s):  
Vahid Azizi ◽  
Shahrbanoo Oryan ◽  
Homayuon Khazali ◽  
Abdolkarim Hosseini

Introduction: The neuropeptide Y (NPY) in the neural circuits of the hypothalamus has a stimulating effect on reproductive activities in mammals. Kisspeptin (KiSS1) is a quintessential neurotransmitter in the reproductive axis which directly stimulates gonadotropin-releasing hormone neurons in the hypothalamus. The distribution of KiSS1 expressing cells in the pituitary was described previously. Despite earlier reports showing the KiSS1 receptor, G-protein coupled receptor 54 (GPR54) expression in the pituitary, the potential physiological roles of kisspeptin at this gland have remained obscure. Accordingly, this study investigated the role of NPY on the relative expression of Kiss1 and Gpr54 genes in the pituitary gland in male Wistar rats. Methods: In general, 20 male Wistar rats weighing 200-250 g in 4 groups (5 in each group) received saline, NPY (2.3 nM), BIBP3226 (NPY receptor antagonist, 7.8 nM), and NPY+ BIBP3226. Then, they received the simultaneous injection of these molecules through the third ventricle of the brain. Finally, the relative mean expressions of Kiss1 and Gpr54 genes in the anterior pituitary were quantitatively analyzed by the real-time polymerase chain reaction. Results: The central injection of NPY increased the relative mean expressions of Kiss1 and Gpr54 genes in the pituitary gland compared to the control group although the injection of BIBP3226 eradicated these effects. However, the gene expression of Gpr54 in the rats receiving NPY coupled with BIBP3226 in hypophysis in comparison to the group receiving only NPY demonstrated a significant reduction (P<0.05). Conclusion: Overall, the central injection of NPY stimulated the gene expression of Kiss1 and Gpr54 in the pituitary gland.


2018 ◽  
Vol 103 (8) ◽  
pp. 1076-1086 ◽  
Author(s):  
João Paulo Cavalcanti-de-Albuquerque ◽  
Grasielle Clotildes Kincheski ◽  
Ruy Andrade Louzada ◽  
Antônio Galina ◽  
Anna Paola Trindade Rocha Pierucci ◽  
...  

Author(s):  
Carmen Rubio ◽  
Esther Lizárraga ◽  
David Álvarez-Cilleros ◽  
Paula Pérez-Pardo ◽  
Patricia Sanmartín-Salinas ◽  
...  

Abstract Aging in mammals is characterized by failure of the homeostatic mechanisms that regulate energy balance. Several mechanisms have been proposed such as the presence of a low-grade chronic inflammation in different tissues, as well as leptin and insulin resistance, but the primary alteration is not fully elucidated. The gut microbiota has recently emerged as a key player in a variety of metabolic and neurological disorders. A main concept in this context is the gut-brain axis that refers to alterations in the gut that mediate effects in the central nervous system, including those related with the control of energy balance. Using 16S rRNA analysis, we demonstrate that aged male Wistar rats have increased presence of mucin-degrading and lipopolysaccharide (LPS)-producing bacteria. In addition, old animals exhibit a lower number of neutral mucin secreting goblet cells, and a decrease of tight junctions and adeherens junctions marker proteins, zonula occludens protein-1(ZO-1) and β-catenin, respectively. These data are compatible with a thinner mucus layer and a weaker gut barrier in older animals that likely facilitate LPS leakage. Our data also show that cholecystokinin (CCK) satiating effect is impaired in aged rats, one of the expected effects of increased LPS leakage. In contrast, no overt signs of gut or systemic inflammation are observed. Changes in microbiota in old male Wistar rats present features of situations of increased adiposity, but different from those of obese animals. They could partly explain the increased adiposity and fat deposition in liver and heart observed here.


2007 ◽  
Vol 292 (3) ◽  
pp. E913-E919 ◽  
Author(s):  
B. M. McGowan ◽  
S. A. Stanley ◽  
N. E. White ◽  
A. Spangeus ◽  
M. Patterson ◽  
...  

The insulin superfamily, characterized by common disulphide bonds, includes not only insulin but also insulin-like peptides such as relaxin-1 and relaxin-3. The actions of relaxin-3 are largely unknown, but recent work suggests a role in regulation of food intake. Relaxin-3 mRNA is highly expressed in the nucleus incertus, which has extensive projections to the hypothalamus, and relaxin immunoreactivity is present in several hypothalamic nuclei. In the rat, relaxin-3 binds and activates both relaxin family peptide receptor 1, which also binds relaxin-1, and a previously orphaned G protein-coupled receptor, RXFP3. These receptors are extensively expressed in the hypothalamus. The aims of these studies were twofold: 1) map the hypothalamic site(s) of the orexigenic action of relaxin-3 and 2) examine the site(s) of neuronal activation following central relaxin-3 administration. After microinjection into hypothalamic sites, human relaxin-3 (H3; 180 pmol) significantly stimulated 0- to 1-h food intake in the supraoptic nucleus (SON), arcuate nucleus (ARC), and the anterior preoptic area (APOA) [SON 0.4 ± 0.2 (vehicle) vs. 2.9 ± 0.5 g (H3), P < 0.001; ARC 0.7 ± 0.3 (vehicle) vs. 2.7 ± 0.2 g (H3), P < 0.05; and APOA 0.8 ± 0.1 (vehicle) vs. 2.2 ± 0.2 g (H3), P < 0.05]. Cumulative food intake was significantly increased ≤8 h following administration into the SON and 4 h into the APOA. A significant increase in Fos-like immunoreactivity was seen in the SON following central relaxin-3 administration. Relaxin-3 stimulates feeding in several hypothalamic nuclei, and these studies provide additional support for relaxin-3 as an important peptide in appetite regulation.


1987 ◽  
Vol 252 (2) ◽  
pp. G195-G199 ◽  
Author(s):  
M. Hashmonai ◽  
V. L. Go ◽  
T. Yaksh ◽  
J. H. Szurszewski

The effects of intravenous, intrathecal, and intracerebroventricular injection of motilin on the interdigestive myoelectric (MMC) activity of the stomach and small intestine were examined in conscious dogs. To monitor electrical activity, electrodes were implanted on the stomach and small bowel. To inject motilin into the central nervous system, catheters were chronically positioned in the intrathecal space at the lumbar level and in one of the lateral cerebral ventricles. In all dogs, intravenous injection of motilin caused a transient increase in the plasma concentration of motilin and initiated gastric MMCs, which propagated aborally to the ileum. Intrathecal and intracerebroventricular injections of motilin did not affect plasma motilin levels and did not induce MMCs. These data suggest that initiation of MMCs after intravenous injections of motilin occurs through receptors for motilin possibly located outside the central nervous system. These data also suggest the hypothesis that initiation of naturally occurring MMCs in the dog may not be dependent on endogenous release of motilin from the central nervous system.


2007 ◽  
Vol 292 (1) ◽  
pp. R575-R585 ◽  
Author(s):  
Éva Szentirmai ◽  
Levente Kapás ◽  
James M. Krueger

Ghrelin, a gut-brain peptide, is best known for its role in the stimulation of feeding and growth hormone release. In the brain, orexin, neuropeptide Y (NPY), and ghrelin are parts of a food intake regulatory circuit. Orexin and NPY are also implicated in maintaining wakefulness. Previous experiments in our laboratory revealed that intracerebroventricular injections of ghrelin induce wakefulness in rats. To further elucidate the possible role of ghrelin in the regulation of arousal, we studied the effects of microinjections of ghrelin into hypothalamic sites, which are implicated in the regulation of feeding and sleep, such as the lateral hypothalamus (LH), medial preoptic area (MPA), and paraventricular nucleus (PVN) on sleep in rats. Sleep responses, motor activity, and food intake after central administration of 0.04, 0.2, or 1 μg (12, 60, or 300 pmol) ghrelin were recorded. Microinjections of ghrelin into the LH had strong wakefulness-promoting effects lasting for 2 h. Wakefulness was also stimulated by ghrelin injection into the MPA and PVN; the effects were confined to the first hour after the injection. Ghrelin's non-rapid-eye-movement sleep-suppressive effect was accompanied by attenuation in the electroencephalographic (EEG) slow-wave activity and changes in the EEG power spectrum. Food consumption was significantly stimulated after microinjections of ghrelin into each hypothalamic site. Together, these results are consistent with the hypothesis that forebrain ghrelinergic mechanisms play a role in the regulation of vigilance, possibly through activating the components of the food intake- and arousal-promoting network formed by orexin and NPY.


PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260546
Author(s):  
Mary J. Obayemi ◽  
Christopher O. Akintayo ◽  
Adesola A. Oniyide ◽  
Ayodeji Aturamu ◽  
Olabimpe C. Badejogbin ◽  
...  

Background Adipose and hepatic metabolic dysfunctions are critical comorbidities that also aggravate insulin resistance in obese individuals. Melatonin is a low-cost agent and previous studies suggest that its use may promote metabolic health. However, its effects on some comorbidities associated with obesity are unknown. Herein, we investigated the hypothesis that melatonin supplementation would attenuate adipose-hepatic metabolic dysfunction in high fat diet (HFD)-induced obesity in male Wistar rats. Materials and methods Twenty-four adult male Wistar rats (n = 6/group) were used: Control group received vehicle (normal saline), obese group received 40% high fat diet, melatonin-treated group received 4 mg/kg of melatonin, and obese plus melatonin group received 40% HFD and melatonin. The treatment lasted for 12 weeks. Results HFD caused increased food intake, body weight, insulin level, insulin resistance and plasma and liver lipid but decreased adipose lipid. In addition, HFD also increased plasma, adipose and liver malondialdehyde, IL-6, uric acid and decreased Glucose-6-phosphate dehydrogenase, glutathione, nitric oxide and circulating obestatin concentration. However, these deleterious effects except food intake were attenuated when supplemented with melatonin. Conclusion Taken together, the present results indicate that HFD exposure causes adipose-hepatic metabolic disturbance in obese animals, which are accompanied by oxidative stress and inflammation. In addition, the present results suggest that melatonin supplementation attenuates adipose-hepatic metabolic dysfunction, accompanying obesity by suppression of oxidative stress/inflammation-dependent mechanism and increasing circulating obestatin.


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