Neuroendocrine regulatory peptide-2 regulates feeding behavior via the orexin system in the hypothalamus

2010 ◽  
Vol 299 (3) ◽  
pp. E394-E401 ◽  
Author(s):  
Koji Toshinai ◽  
Hideki Yamaguchi ◽  
Haruaki Kageyama ◽  
Takashi Matsuo ◽  
Keiichi Koshinaka ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Locomotor Activity ◽  
Food Intake ◽  
Body Temperature ◽  
Feeding Behavior ◽  
Energy Homeostasis ◽  
Protein A ◽  
Mrna Levels ◽  
Intracerebroventricular Administration ◽  
Regulatory Peptide

Neuroendocrine regulatory peptide (NERP)-1 and NERP-2 are derived from distinct regions of VGF, a neurosecretory protein. Vgf−/− mice exhibit dwarfism and hypermetabolic rates, suggesting that VGF or VGF-derived peptides play important roles in energy metabolism. Here, we examined the role of NERPs in the central regulation of feeding and energy homeostasis. We attempted to identify NERPs expressing neurons in rats by immunohistochemistry. We studied the effects of intracerebroventricular (icv) administration of NERP-2 on feeding, body temperature, oxygen consumption, and locomotor activity in rats and mice. Intracerebroventricular administration of NERP-2, but not NERP-1 or a form of NERP-2 bearing a COOH-terminal glycine extension, increased food intake in rats. We investigated the downstream signal of NERP-2 on the basis of studies of NERP-2-induced feeding with neutralization of orexins, neuropeptide Y, or agouti-related protein. NERP-2 expression localized to the lateral hypothalamus (LH) and the dorsomedial perifornical hypothalamus in rats, colocalizing with orexins that activate feeding behavior and arousal. NERP-2 administration induced Fos protein, a marker of neuronal activation, in the orexin-immunoreactive neurons. Vgf mRNA levels were upregulated in the rat LH upon food deprivation. Intracerebroventricular administration of NERP-2 also increased body temperature, oxygen consumption, and locomotor activity in rats. Treatment with anti-NERP-2 IgG decreased food intake. NERP-2-induced bioactivities could be abrogated by administration of anti-orexins IgG or orexin receptor antagonists. NERP-2 did not induce food intake or locomotor activity in orexin-deficient mice. Our findings indicate that hypothalamic NERP-2 plays a role in the control of food intake and energy homeostasis via the orexin pathway. Thus, VGF serves as a precursor of multiple bioactive peptides exerting a diverse set of neuroendocrine functions.

Effect of intracerebroventricular α-MSH on food intake, adiposity, c-Fos induction, and neuropeptide expression

2000 ◽  
Vol 279 (2) ◽  
pp. R695-R703 ◽  
Author(s):  
Julie E. McMinn ◽  
Charles W. Wilkinson ◽  
Peter J. Havel ◽  
Stephen C. Woods ◽  
Michael W. Schwartz
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Homeostasis ◽  
Melanocortin Receptor ◽  
Mrna Levels ◽  
Melanocyte Stimulating Hormone ◽  
The Third ◽  
Chronic Infusion ◽  
Plasma Insulin Levels ◽  
Cumulative Food Intake

α-Melanocyte-stimulating hormone (α-MSH) is a hypothalamic neuropeptide proposed to play a key role in energy homeostasis. To investigate the behavioral, metabolic, and hypothalamic responses to chronic central α-MSH administration, α-MSH was infused continuously into the third cerebral ventricle of rats for 6 days. Chronic α-MSH infusion reduced cumulative food intake by 10.7% ( P < 0.05 vs. saline) and body weight by 4.3% ( P < 0.01 vs. saline), which in turn lowered plasma insulin levels by 29.3% ( P < 0.05 vs. saline). However, α-MSH did not cause adipose-specific wasting nor did it alter hypothalamic neuropeptide mRNA levels. Central α-MSH infusion acutely activated neurons in forebrain areas such as the hypothalamic paraventricular nucleus, as measured by a 254% increase in c-Fos-like immunoreactivity ( P < 0.01 vs. saline), as well as satiety pathways in the hindbrain. Our findings suggest that, although an increase of central melanocortin receptor signaling acutely reduces food intake and body weight, its anorectic potency wanes during chronic infusion and causes only a modest decrease of body weight.

scholarly journals A potent neuropeptide Y antagonist, 1229U91, suppressed spontaneous food intake in Zucker fatty rats

1998 ◽  
Vol 274 (5) ◽  
pp. R1500-R1504 ◽  
Author(s):  
A. Ishihara ◽  
T. Tanaka ◽  
A. Kanatani ◽  
T. Fukami ◽  
M. Ihara ◽  
...  
Keyword(s):  
Food Intake ◽  
Neuropeptide Y ◽  
Feeding Behavior ◽  
Physiological Role ◽  
Abnormal Behavior ◽  
Zucker Rats ◽  
Intracerebroventricular Administration ◽  
Feeding Suppression ◽  
Npy Antagonist

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.

Activity and energy expenditure in laying hens

1976 ◽  
Vol 86 (3) ◽  
pp. 471-473 ◽  
Author(s):  
M. Van Kampen
Keyword(s):  
Oxygen Consumption ◽  
Locomotor Activity ◽  
Body Temperature ◽  
Energy Expenditure ◽  
Oxygen Uptake ◽  
Heat Production ◽  
Energy Cost ◽  
Laying Hens ◽  
Different Types ◽  
Nesting Activity

SummaryThe energy cost of nesting activity and oviposition of hens in different environments has been determined.The oxygen consumption of hens on a wire floor reached a peak during the last 15 min before oviposition. However, the oxygen uptake of hens accustomed to a litter floor had fallen to a minimum at this time.The energy cost of expelling the egg is minimal. There is a good correlation between the locomotor activity and the heat production.The variations in heat production and body temperature on different types of floors are explicable by the differences in nesting activity.

Measurement of oxygen consumption and locomotor activity in monosodium glutamate-induced obesity.

1978 ◽  
Vol 234 (5) ◽  
pp. E532 ◽  
Author(s):  
T K Poon ◽  
D P Cameron
Keyword(s):  
Oxygen Consumption ◽  
Locomotor Activity ◽  
Food Intake ◽  
Energy Expenditure ◽  
Monosodium Glutamate ◽  
Neonatal Administration ◽  
And Control

Oxygen consumption and locomotor activity were studied in mice developing obesity after neonatal administration of monosodium glutamate (MSG) and in untreated controls. MSG-treated mice became obese in the absence of increased food intake. Locomotor activity was significantly less in MSG-treated mice 2, 10, and 20 wk after weaning. Oxygen consumption expressed in terms of the Lee index was not significantly different at 2 wk after weaning although at 10 and 20 wk it was significantly lower in MSG-treated mice. Plasma thyroxine was not different between MSG-treated and control mice. It is suggested that diminished energy expenditure is the major factor in the etiology of obesity after neonatal administration of MSG.

Lipopolysaccharide induces fever and depresses locomotor activity in unrestrained mice

1994 ◽  
Vol 266 (1) ◽  
pp. R125-R135 ◽  
Author(s):  
W. Kozak ◽  
C. A. Conn ◽  
M. J. Kluger
Keyword(s):  
Locomotor Activity ◽  
Food Intake ◽  
Body Temperature ◽  
Guinea Pigs ◽  
Time Course ◽  
Laboratory Animals ◽  
Dependent Manner ◽  
Basic Biology ◽  
Freely Moving ◽  
Dose Dependent

The purpose of this study was to characterize the basic biology of fever to lipopolysaccharide (LPS) in unrestrained mice. Although LPS has been shown to induce fevers in many laboratory animals (e.g., rats, guinea pigs, rabbits), there is some question of whether LPS causes a fall or rise in body temperature (Tb) in mice. Tb was measured by biotelemetry in unrestrained mice maintained at an ambient temperature of 30 degrees C. Intraperitoneal injections of LPS at doses of 1.0, 2.5, and 3.0 mg/kg induced dose-independent prompt decreases of Tb for 5.7 h. After this postinjection reduction, Tb increased and reached a peak at approximately 24 h postinjection. The peak rises in Tb were dose dependent. Changes in Tb due to LPS were accompanied by suppression of locomotor activity. Indomethacin, at a dose that did not affect normal Tb, enhanced the temperature-lowering effect of LPS as well as inhibited the febrile rise of Tb after LPS. Indomethacin did not modify the reduction in activity caused by the injections of LPS. Food intake of the mice was decreased by LPS in a dose-dependent manner, and tolerance developed to a second injection of LPS. We conclude that freely moving mice can develop pronounced and reproducible fevers in response to LPS, which is different in time course, dose-dependent profile, induction of pyrogenic tolerance profile, and mode of inhibition by indomethacin from those responses that have been observed in other species studied so far.

Orexin activation precedes increased NPY expression, hyperphagia, and metabolic changes in response to sleep deprivation

2010 ◽  
Vol 298 (3) ◽  
pp. E726-E734 ◽  
Author(s):  
Paulo José Forcina Martins ◽  
Marina Soares Marques ◽  
Sergio Tufik ◽  
Vânia D'Almeida
Keyword(s):  
Body Weight ◽  
Energy Balance ◽  
Food Intake ◽  
Sleep Deprivation ◽  
Weight Control ◽  
Time Course ◽  
Energy Homeostasis ◽  
Negative Energy ◽  
Negative Energy Balance ◽  
Mrna Levels

Several pieces of evidence support that sleep duration plays a role in body weight control. Nevertheless, it has been assumed that, after the identification of orexins (hypocretins), the molecular basis of the interaction between sleep and energy homeostasis has been provided. However, no study has verified the relationship between neuropeptide Y (NPY) and orexin changes during hyperphagia induced by sleep deprivation. In the current study we aimed to establish the time course of changes in metabolite, endocrine, and hypothalamic neuropeptide expression of Wistar rats sleep deprived by the platform method for a distinct period (from 24 to 96 h) or sleep restricted for 21 days (SR-21d). Despite changes in the stress hormones, we found no changes in food intake and body weight in the SR-21d group. However, sleep-deprived rats had a 25–35% increase in their food intake from 72 h accompanied by slight weight loss. Such changes were associated with increased hypothalamus mRNA levels of prepro-orexin (PPO) at 24 h followed by NPY at 48 h of sleep deprivation. Conversely, sleep recovery reduced the expression of both PPO and NPY, which rapidly brought the animals to a hypophagic condition. Our data also support that sleep deprivation rapidly increases energy expenditure and therefore leads to a negative energy balance and a reduction in liver glycogen and serum triacylglycerol levels despite the hyperphagia. Interestingly, such changes were associated with increased serum levels of glucagon, corticosterone, and norepinephrine, but no effects on leptin, insulin, or ghrelin were observed. In conclusion, orexin activation accounts for the myriad changes induced by sleep deprivation, especially the hyperphagia induced under stress and a negative energy balance.

scholarly journals Viral Infection Drives the Regulation of Feeding Behavior Related Genes in Salmo salar

2021 ◽  
Vol 22 (21) ◽  
pp. 11391
Author(s):  
David Muñoz ◽  
Ricardo Fuentes ◽  
Beatriz Carnicero ◽  
Andrea Aguilar ◽  
Nataly Sanhueza ◽  
...  
Keyword(s):  
Food Intake ◽  
Viral Infection ◽  
Feeding Behavior ◽  
Energy Homeostasis ◽  
Infectious Pancreatic Necrosis Virus ◽  
Complex Activity ◽  
Fish Remains ◽  
Pancreatic Necrosis Virus ◽  
The Brain

The feeding behavior in fish is a complex activity that relies on the ability of the brain to integrate multiple signals to produce appropriate responses in terms of food intake, energy expenditure, and metabolic activity. Upon stress cues including viral infection or mediators such as the proinflammatory cytokines, prostaglandins, and cortisol, both Pomc and Npy/Agrp neurons from the hypothalamus are stimulated, thus triggering a response that controls both energy storage and expenditure. However, how appetite modulators or neuro-immune cues link pathogenesis and energy homeostasis in fish remains poorly understood. Here, we provide the first evidence of a molecular linkage between inflammation and food intake in Salmon salar. We show that in vivo viral challenge with infectious pancreatic necrosis virus (IPNV) impacts food consumption by activating anorexic genes such as mc4r, crf, and pomcb and 5-HT in the brain of S. salar. At the molecular level, viral infection induces an overall reduction in lipid content in the liver, favoring the production of AA and EPA associated with the increment of elovl2 gene. In addition, infection upregulates leptin signaling and inhibits insulin signaling. These changes are accompanied by a robust inflammatory response represented by the increment of Il-1b, Il-6, Tnfa, and Pge2 as well as an increased cortisol level in vivo. Thus, we propose a model in which hypothalamic neurons respond to inflammatory cytokines and stress-related molecules and interact with appetite induction/inhibition. These findings provide evidence of crosstalk between pathogenesis-driven inflammation and hypothalamic–pituitary–adrenocortical axes in stress-induced food intake behavior in fish.

Effect of glucagon-like peptide-1 and -2 on regulation of food intake, body temperature and locomotor activity in the Japanese quail

2007 ◽  
Vol 415 (2) ◽  
pp. 102-107 ◽  
Author(s):  
Saad Shousha ◽  
Keiko Nakahara ◽  
Tetsuo Nasu ◽  
Takumi Sakamoto ◽  
Noboru Murakami
Keyword(s):  
Locomotor Activity ◽  
Food Intake ◽  
Body Temperature ◽  
Japanese Quail ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals OR04-03 Calcitonin Receptor Expressing Neurons in the PVH Regulate Feeding Behavior

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Ian Enrique Gonzalez ◽  
Wenwen Cheng ◽  
Warren Pan ◽  
Chunxia Lu ◽  
Julliana Ramirez-Matias ◽  
...  
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Feeding Behavior ◽  
Tetanus Toxin ◽  
Energy Homeostasis ◽  
Balance Control ◽  
Brain Regions ◽  
Calcitonin Receptor ◽  
Cumulative Food Intake

Abstract The paraventricular nucleus of the hypothalamus (PVH) is a brain region crucial for energy homeostasis. Abnormal PVH development or damage leads to hyperphagic obesity and energy expenditure deficits underscoring the importance of PVH neuronal activity in energy balance control. Application of salmon calcitonin (sCT) to the PVH suppresses feeding and calcitonin receptor (CalcR) is highly expressed in the PVH of rodents suggesting that CalcR-expressing PVH neurons contribute to energy homeostasis. In situ hybridization reveals that many CalcRPVH neurons express melanocortin-4 receptor (MC4R), a receptor required for normal feeding behavior. To investigate the physiologic roles of CalcRPVH neurons, we generated CalcR-2a-Cre knock-in mice to manipulate CalcR-expressing cells. Deletion of MC4R from CalcR expressing cells using Cre-loxP technology resulted in profound obesity in both male and female mice by 16 weeks of age. This weight gain was attributable to hyperphagia, as cumulative food intake of the MC4R deleted mice was significantly greater than the controls and energy expenditure measurements acquired through CLAMS analysis were not significantly different. To determine the brain regions engaged by CalcRPVH neurons, we used anterograde Cre-dependent viral tracing reagents injected into the PVH of CalcR-Cre mice, and found that CalcRPVH neurons project to brain regions implicated in energy balance control, including the nucleus of the solitary tract and the parabrachial nucleus. To assess the acute effects of activating CalcRPVH neurons, we used DREADD technology to chemogenetically activate CalcRPVH neurons. CalcRPVH neuron activation suppressed feeding but had no significant effect on energy expenditure. To determine if the activity of CalcRPVH neurons is required for energy homeostasis, we silenced them using Cre-dependent tetanus toxin virus. Male mice with tetanus toxin silenced CalcRPVH neurons were obese 7 weeks following injection in part due to greater cumulative food intake; CLAMS analysis revealed no differences in energy expenditure. Mice with silenced CalcRPVH neurons as well as mice with CalcR deleted from the PVH had normal anorectic responses to sCT, suggesting sCT-induced anorexia does not require CalcRPVH neurons or CalcR expression in the PVH. Taken together, these findings suggest CalcRPVH neurons are an essential component of feeding and energy homeostatic circuitry.

Physiology of transgenic mice with brown fat ablation: obesity is due to lowered body temperature

1998 ◽  
Vol 274 (2) ◽  
pp. R287-R293 ◽  
Author(s):  
Susanne Klaus ◽  
Heike Münzberg ◽  
Christiane Trüloff ◽  
Gerhard Heldmaier
Keyword(s):  
Locomotor Activity ◽  
Food Intake ◽  
Body Temperature ◽  
Transgenic Mice ◽  
Uncoupling Protein ◽  
Core Body Temperature ◽  
Physiological Basis ◽  
Brown Adipose ◽  
Temperature Levels ◽  
Food Assimilation

We investigated the physiological basis for development of obesity in uncoupling protein-diphtheria toxin A chain (UCP-DTA) transgenic mice. In these mice the promoter of the brown adipose tissue (BAT)-specific UCP was used to drive expression of DTA, resulting in decreased BAT function and development of obesity and insulin resistance (Lowell, B. B., S. V. Susulic, A. Hamann, J. A. Lawitts, J. Himms-Hagen, B. B. Boyer, L. Kozak, and J. S. Flier. Nature 366: 740–742, 1994). In adult UCP-DTA mice, we measured food intake and food assimilation, locomotor activity, metabolic rate, and body temperature in comparison to control animals. No differences could be observed in food intake or assimilation and locomotor activity. Weight-specific metabolic rates at temperatures between 20 and 37°C, however, were consistently lower in transgenic mice. Continuous telemetric recording of core body temperature showed that transgenic mice displayed a downshift in body temperature levels of ∼0.9°C. In summary, we provide evidence that attenuated body temperature levels alone can be responsible for development of obesity and that BAT thermogenesis is a major determinant of body temperature levels in rodents.

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