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.

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 Depletion of Alpha-Melanocyte-Stimulating Hormone Induces Insatiable Appetite and Gains in Energy Reserves and Body Weight in Zebrafish

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 941
Author(s):  
Yang-Wen Hsieh ◽  
Yi-Wen Tsai ◽  
Hsin-Hung Lai ◽  
Chi-Yu Lai ◽  
Chiu-Ya Lin ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Homeostasis ◽  
Body Weight Gain ◽  
Genetically Engineered ◽  
Melanocortin Receptor ◽  
Synthetic Analog ◽  
Melanocortin System ◽  
Releasing Hormone ◽  
Melanocyte Stimulating Hormone ◽  
Stimulating Hormone

The functions of anorexigenic neurons secreting proopiomelanocortin (POMC)/alpha-melanocyte-stimulating hormone (α-MSH) of the melanocortin system in the hypothalamus in vertebrates are energy homeostasis, food intake, and body weight regulation. However, the mechanisms remain elusive. This article reports on zebrafish that have been genetically engineered to produce α-MSH mutants, α-MSH−7aa and α-MSH−8aa, selectively lacking 7 and 8 amino acids within the α-MSH region, but retaining most of the other normal melanocortin-signaling (Pomc-derived) peptides. The α-MSH mutants exhibited hyperphagic phenotypes leading to body weight gain, as observed in human patients and mammalian models. The actions of several genes regulating appetite in zebrafish are similar to those in mammals when analyzed using gene expression analysis. These include four selected orexigenic genes: Promelanin-concentrating hormone (pmch), agouti-related protein 2 (agrp2), neuropeptide Y (npy), and hypothalamic hypocretin/orexin (hcrt). We also study five selected anorexigenic genes: Brain-derived neurotrophic factor (bdnf), single-minded homolog 1-a (sim1a), corticotropin-releasing hormone b (crhb), thyrotropin-releasing hormone (trh), and prohormone convertase 2 (pcsk2). The orexigenic actions of α-MSH mutants are rescued completely after hindbrain ventricle injection with a synthetic analog of α-MSH and a melanocortin receptor agonist, Melanotan II. We evaluate the adverse effects of MSH depletion on energy balance using the Alamar Blue metabolic rate assay. Our results show that α-MSH is a key regulator of POMC signaling in appetite regulation and energy expenditure, suggesting that it might be a potential therapeutic target for treating human obesity.

Glucocorticoids reverse leptin effects on food intake and body fat in mice without increasing NPY mRNA

1999 ◽  
Vol 277 (4) ◽  
pp. E708-E716 ◽  
Author(s):  
Joel M. Solano ◽  
Lauren Jacobson
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Body Fat ◽  
Mrna Levels ◽  
Plasma Insulin Levels ◽  
Significant Attenuation ◽  
Induced Changes ◽  
Leptin Expression ◽  
Stimulation Of

Glucocorticoid stimulation of appetite and leptin expression conflicts with leptin inhibition of food intake and suggests that glucocorticoids reduce sensitivity to leptin. To determine if glucocorticoids impair feeding and metabolic responses to leptin, we measured leptin-induced changes in food intake, body weight, hormones, carcass fat, and hypothalamic neuropeptide Y (NPY) mRNA in adrenalectomized mice with and without corticosterone replacement. Leptin infusion (0.5 μg/h) significantly decreased food intake and body weight in adrenalectomized mice. Corticosterone replacement approximating normal 24-h mean levels restored food intake but did not permit weight gain equivalent to PBS-infused controls. Corticosterone levels comparable to stress-induced production completely reversed leptin-induced reductions in weight gain and body fat, despite significant attenuation by leptin of corticosterone-induced increases in plasma insulin levels. Glucocorticoid replacement increased food intake without reversing leptin inhibition of hypothalamic NPY mRNA levels. We conclude that glucocorticoid levels within the physiological range can interfere with leptin action and that glucocorticoid effects are at least partly independent of NPY.

Central Histamine, the H3-Receptor and Obesity Therapy

2019 ◽  
Vol 18 (7) ◽  
pp. 516-522
Author(s):  
Néstor F. Díaz ◽  
Héctor Flores-Herrera ◽  
Guadalupe García-López ◽  
Anayansi Molina-Hernández
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Animal Studies ◽  
Energy Homeostasis ◽  
Receptor Activation ◽  
Receptor Ligands ◽  
Histaminergic System ◽  
H3 Receptor ◽  
Weight One ◽  
The Central Nervous System

The brain histaminergic system plays a pivotal role in energy homeostasis, through H1- receptor activation, it increases the hypothalamic release of histamine that decreases food intake and reduces body weight. One way to increase the release of hypothalamic histamine is through the use of antagonist/inverse agonist for the H3-receptor. Histamine H3-receptors are auto-receptors and heteroreceptors located on the presynaptic membranes and cell soma of neurons, where they negatively regulate the synthesis and release of histamine and other neurotransmitters in the central nervous system. Although several compounds acting as H3-receptor antagonist/inverse agonists have been developed, conflicting results have been reported and only one has been tested as anti-obesity in humans. Animal studies revealed the opposite effect in food intake, energy expeditor, and body weight, depending on the drug, spice, and route of administration, among others. The present review will explore the state of art on the effects of H3-receptor ligands on appetite and body-weight, going through the following: a brief overview of the circuit involved in the control of food intake and energy homeostasis, the participation of the histaminergic system in food intake and body weight, and the H3-receptor as a potential therapeutic target for obesity.

scholarly journals Neonatal nutritional programming impairs adiponectin effects on energy homeostasis in adult life of male rats

2018 ◽  
Vol 315 (1) ◽  
pp. E29-E37 ◽  
Author(s):  
Mariana Peduti Halah ◽  
Paula Beatriz Marangon ◽  
Jose Antunes-Rodrigues ◽  
Lucila L. K. Elias
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Food Intake ◽  
White Adipose Tissue ◽  
Energy Homeostasis ◽  
Body Weight Gain ◽  
Adult Life ◽  
Male Rats ◽  
Nutritional Programming

Neonatal nutritional changes induce long-lasting effects on energy homeostasis. Adiponectin influences food intake and body weight. The aim of this study was to investigate the effects of neonatal nutritional programming on the central stimulation of adiponectin. Male Wistar rats were divided on postnatal (PN) day 3 in litters of 3 (small litter, SL), 10 (normal litter, NL), or 16 pups/dam (large litter, LL). We assessed body weight gain for 60 days, adiponectin concentration, and white adipose tissue weight. We examined the response of SL, NL, and LL rats on body weight gain, food intake, oxygen consumption (V̇o2), respiratory exchange ratio (RER), calorimetry, locomotor activity, phosphorylated-AMP-activated protein kinase (AMPK) expression in the hypothalamus, and uncoupling protein (UCP)-1 in the brown adipose tissue after central stimulus with adiponectin. After weaning, SL rats maintained higher body weight gain despite similar food intake compared with NL rats. LL rats showed lower body weight at weaning, with a catch up afterward and higher food intake. Both LL and SL groups had decreased plasma concentrations of adiponectin at PN60. SL rats had increased white adipose tissue. Central injection of adiponectin decreased body weight and food intake and increased V̇o2, RER, calorimetry, p-AMPK and UCP- 1 expression in NL rats, but it had no effect on SL and LL rats, compared with the respective vehicle groups. In conclusion, neonatal under- and overfeeding induced an increase in body weight gain in juvenile and early adult life. Unresponsiveness to central effects of adiponectin contributes to the imbalance of the energy homeostasis in adult life induced by neonatal nutritional programming.

scholarly journals Effect of chronic infusion of olanzapine and clozapine on food intake and body weight gain in male and female rats

Life Sciences ◽  
2007 ◽  
Vol 81 (12) ◽  
pp. 1024-1030 ◽  
Author(s):  
SuJean Choi ◽  
Briana DiSilvio ◽  
JayLynn Unangst ◽  
John D. Fernstrom
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Body Weight Gain ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats ◽  
Chronic Infusion

scholarly journals Antiobesity Effects of the β-Cell Hormone Amylin in Diet-Induced Obese Rats: Effects on Food Intake, Body Weight, Composition, Energy Expenditure, and Gene Expression

Endocrinology ◽  
2006 ◽  
Vol 147 (12) ◽  
pp. 5855-5864 ◽  
Author(s):  
Jonathan D. Roth ◽  
Heather Hughes ◽  
Eric Kendall ◽  
Alain D. Baron ◽  
Christen M. Anderson
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Respiratory Quotient ◽  
Metabolic Effects ◽  
Mrna Levels ◽  
Lean Tissue ◽  
Reduced Body ◽  
Diet Induced Obesity ◽  
Cell Hormone

Effects of amylin and pair feeding (PF) on body weight and metabolic parameters were characterized in diet-induced obesity-prone rats. Peripherally administered rat amylin (300 μg/kg·d, 22d) reduced food intake and slowed weight gain: approximately 10% (P &lt; 0.05), similar to PF. Fat loss was 3-fold greater in amylin-treated rats vs. PF (P &lt; 0.05). Whereas PF decreased lean tissue (P &lt; 0.05 vs. vehicle controls; VEH), amylin did not. During wk 1, amylin and PF reduced 24-h respiratory quotient (mean ± se, 0.82 ± 0.0, 0.81 ± 0.0, respectively; P &lt; 0.05) similar to VEH (0.84 ± 0.01). Energy expenditure (EE mean ± se) tended to be reduced by PF (5.67 ± 0.1 kcal/h·kg) and maintained by amylin (5.86 ± 0.1 kcal/h·kg) relative to VEH (5.77 ± 0.0 kcal/h·kg). By wk 3, respiratory quotient no longer differed; however, EE increased with amylin treatment (5.74 ± 0.09 kcal/·kg; P &lt; 0.05) relative to VEH (5.49 ± 0.06) and PF (5.38 ± 0.07 kcal/h·kg). Differences in EE, attributed to differences in lean mass, argued against specific amylin-induced thermogenesis. Weight loss in amylin and pair-fed rats was accompanied by similar increases arcuate neuropeptide Y mRNA (P &lt; 0.05). Amylin treatment, but not PF, increased proopiomelanocortin mRNA levels (P &lt; 0.05 vs. VEH). In a rodent model of obesity, amylin reduced body weight and body fat, with relative preservation of lean tissue, through anorexigenic and specific metabolic effects.

Role of central melanocortins in endotoxin-induced anorexia

1999 ◽  
Vol 276 (3) ◽  
pp. R864-R871 ◽  
Author(s):  
Qin-Heng Huang ◽  
Victor J. Hruby ◽  
Jeffrey B. Tatro
Keyword(s):  
Locomotor Activity ◽  
Food Intake ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Phase Response ◽  
Melanocortin Receptor ◽  
Receptor Subtype ◽  
Microbial Infection ◽  
Melanocyte Stimulating Hormone ◽  
The Central Nervous System

Inflammation and microbial infection produce symptoms, including fever, anorexia, and hypoactivity, that are thought to be mediated by endogenous proinflammatory cytokines. Melanocortins are known to act centrally to suppress effects on fever and other sequelae of proinflammatory cytokine actions in the central nervous system, but the roles of melanocortins in anorexia and hypoactivity occurring during the acute phase response are unknown. The present study was designed to determine the effects of exogenous and endogenous α-melanocyte stimulating hormone (α-MSH) on lipopolysaccharide (LPS)-induced anorexia in relation to their effects on fever. Rats were fasted overnight to promote feeding behavior, then injected intraperitoneally with LPS (100 μg/kg ip), followed 30 min later by intracerebroventricular injection of either α-MSH or the melanocortin receptor subtype 3/subtype 4 (MC3-R/MC4-R) antagonist SHU-9119. Food intake, locomotor activity, and body temperature (Tb) were monitored during the ensuing 24-h period. Each of two intracerebroventricular doses of α-MSH (30 and 300 ng) potentiated the suppressive effects of LPS on food intake and locomotion, despite the fact that the higher dose alleviated LPS-induced fever. In control rats that were not treated with LPS, only the higher dose of α-MSH significantly inhibited food intake, and Tband locomotor activity were unaffected. To assess the roles of endogenous central melanocortins, LPS-treated rats received intracerebroventricular SHU-9119 (200 ng). Central MC3-R/MC4-R blockade did not affect Tbor food intake in the absence of LPS treatment, but it reversed the LPS-induced reduction in 24-h food intake and increased LPS-induced fever without altering the LPS-induced suppression of locomotion. Taken together, the results suggest that exogenous and endogenous melanocortins acting centrally exert divergent influences on different aspects of the acute phase response, suppressing LPS-induced fever but contributing to LPS-induced anorexia and hypoactivity.

scholarly journals The Effect of a 2-Week Red Ginseng Supplementation on Food Efficiency and Energy Metabolism in Mice

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1726
Author(s):  
Hyejung Hwang ◽  
Jisu Kim ◽  
Kiwon Lim
Keyword(s):  
Body Weight ◽  
Energy Metabolism ◽  
Food Intake ◽  
Weight Control ◽  
Fat Oxidation ◽  
Substrate Utilization ◽  
Mrna Levels ◽  
Red Ginseng ◽  
Energy Substrate ◽  
Metabolism Regulation

Red ginseng (RG) ingestion reportedly affects body weight, food intake, and fat accumulation reduction. It also induces changes in energy metabolism regulation and glycemic control. Previously, 2-week RG ingestion with endurance training was found to enhance fat oxidation during exercise. However, such effects on energy metabolism and the expression of mRNAs related to energy substrate utilization in resting mice (untrained mice) are still unclear. Here, we determined the effect of RG on energy metabolism and substrate utilization in untrained male mice. Twenty-four mice were separated into an RG group that received a daily dosage of 1 g/kg RG for 2 weeks, and a control (CON). Energy expenditure, blood and tissue glycogen levels, and expression of mRNAs related to energy substrate utilization in muscles were measured before and 2 weeks after treatment. Total food intake was significantly lower in the RG than in the CON group (p < 0.05), but final body weights did not differ. Carbohydrate and fat oxidation over 24 h did not change in either group. There were no significant differences in gastrocnemius GLUT4, MCT1, MCT4, FAT/CD36, and CPT1b mRNA levels between groups. Thus, the effects of RG ingested during rest differ from the effects of RG ingestion in combination with endurance exercise; administering RG to untrained mice for 2 weeks did not change body weight and energy metabolism. Therefore, future studies should consider examining the RG ingestion period and dosage for body weight control and improving energy metabolism.

scholarly journals LGR4 and Its Ligands, R-Spondin 1 and R-Spondin 3, Regulate Food Intake in the Hypothalamus of Male Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (2) ◽  
pp. 429-440 ◽  
Author(s):  
Ji-Yao Li ◽  
Biaoxin Chai ◽  
Weizhen Zhang ◽  
Danielle M. Fritze ◽  
Chao Zhang ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Food Intake ◽  
Neuropeptide Y ◽  
Paraventricular Nucleus ◽  
Median Eminence ◽  
Energy Homeostasis ◽  
Male Rats ◽  
The Third ◽  
The Brain

The hypothalamus plays a key role in the regulation of feeding behavior. Several hypothalamic nuclei, including the arcuate nucleus (ARC), paraventricular nucleus, and ventromedial nucleus of the hypothalamus (VMH), are involved in energy homeostasis. Analysis of microarray data derived from ARC revealed that leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) is highly expressed. LGR4, LGR5, and LGR6 form a subfamily of closely related receptors. Recently, R-spondin (Rspo) family proteins were identified as ligands of the LGR4 subfamily. In the present study, we investigated the distribution and function of LGR4–LGR6 and Rspos (1–4) in the brain of male rat. In situ hybridization showed that LGR4 is expressed in the ARC, VMH, and median eminence of the hypothalamus. LGR4 colocalizes with neuropeptide Y, proopiomelanocortin, and brain-derived neurotrophic factor neurons. LGR5 is not detectable with in situ hybridization; LGR6 is only expressed in the epithelial lining of the lower portion of the third ventricle and median eminence. Rspo1 is expressed in the VMH and down-regulated with fasting. Rspo3 is expressed in the paraventricular nucleus and also down-regulated with fasting. Rspos 1 and 3 colocalize with the neuronal marker HuD, indicating that they are expressed by neurons. Injection of Rspo1 or Rspo3 into the third brain ventricle inhibited food intake. Rspo1 decreased neuropeptide Y and increased proopiomelanocortin expression in the ARC. Rspo1 and Rspo3 mRNA is up-regulated by insulin. These data indicate that Rspo1 and Rspo3 and their receptor LGR4 form novel circuits in the brain to regulate energy homeostasis.

Sign in / Sign up

Export Citation Format

Share Document