scholarly journals Central infusions of leptin and GLP-1-(7-36) amide differentially stimulate c-FLI in the rat brain

1996 ◽  
Vol 271 (4) ◽  
pp. R1096-R1100 ◽  
Author(s):  
G. Van Dijk ◽  
T. E. Thiele ◽  
J. C. Donahey ◽  
L. A. Campfield ◽  
F. J. Smith ◽  
...  
Keyword(s):  
Food Intake ◽  
Area Postrema ◽  
Hypothalamic Nucleus ◽  
Dark Phase ◽  
Short Term ◽  
Dorsomedial Hypothalamus ◽  
Lateral Parabrachial Nucleus ◽  
The Central Nervous System ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Recently, glucagon-like peptide-1-(7-36) amide (GLP-1) and leptin have been implicated in the regulation of food intake. In the present study, we compared the effects of third ventricular administration (i3vt) of leptin (3.5 micrograms) and GLP-1 (10.0 micrograms) on short-term food intake and c-Fos-like immunoreactivity (c-FLI) in hypothalamic, limbic, and hindbrain areas in the rat. Relative to controls, infusion of leptin or GLP-1 (3 h before lights off) significantly reduced food intake over the first 2 h in the dark phase (53 and 63%, respectively). In different rats, infusion of leptin or GLP-1 elevated c-FLI in the paraventricular hypothalamus and central amygdala. Furthermore, leptin selectively elevated c-FLI in the dorsomedial hypothalamus, whereas GLP-1 selectively elevated c-FLI in the nucleus of the solitary tract, area postrema, lateral parabrachial nucleus, and arcuate hypothalamic nucleus. The fact that most of the c-FLI after leptin or GLP-1 administration was observed in separate regions within the central nervous system (CNS) suggests different roles for leptin and GLP-1 in the CNS regulation of food intake and body weight.

scholarly journals Adjustment of Whey:Casein Ratio from 20:80 to 60:40 in Milk Formulation Affects Food Intake and Brainstem and Hypothalamic Neuronal Activation and Gene Expression in Laboratory Mice

Foods ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 658
Author(s):  
Erin L. Wood ◽  
David G. Christian ◽  
Mohammed Arafat ◽  
Laura K. McColl ◽  
Colin G. Prosser ◽  
...  
Keyword(s):  
Food Intake ◽  
Area Postrema ◽  
Energy Levels ◽  
Early Gene ◽  
Hypothalamic Nucleus ◽  
Laboratory Mice ◽  
Neuronal Activation ◽  
Short Term ◽  
Animal Milk ◽  
The Impact

Adjustment of protein content in milk formulations modifies protein and energy levels, ensures amino acid intake and affects satiety. The shift from the natural whey:casein ratio of ~20:80 in animal milk is oftentimes done to reflect the 60:40 ratio of human milk. Studies show that 20:80 versus 60:40 whey:casein milks differently affect glucose metabolism and hormone release; these data parallel animal model findings. It is unknown whether the adjustment from the 20:80 to 60:40 ratio affects appetite and brain processes related to food intake. In this set of studies, we focused on the impact of the 20:80 vs. 60:40 whey:casein content in milk on food intake and feeding-related brain processes in the adult organism. By utilising laboratory mice, we found that the 20:80 whey:casein milk formulation was consumed less avidly and was less preferred than the 60:40 formulation in short-term choice and no-choice feeding paradigms. The relative PCR analyses in the hypothalamus and brain stem revealed that the 20:80 whey:casein milk intake upregulated genes involved in early termination of feeding and in an interplay between reward and satiety, such as melanocortin 3 receptor (MC3R), oxytocin (OXT), proopiomelanocortin (POMC) and glucagon-like peptide-1 receptor (GLP1R). The 20:80 versus 60:40 whey:casein formulation intake differently affected brain neuronal activation (assessed through c-Fos, an immediate-early gene product) in the nucleus of the solitary tract, area postrema, ventromedial hypothalamic nucleus and supraoptic nucleus. We conclude that the shift from the 20:80 to 60:40 whey:casein ratio in milk affects short-term feeding and relevant brain processes.

scholarly journals Intrameal Hepatic Portal and Intraperitoneal Infusions of Glucagon-Like Peptide-1 Reduce Spontaneous Meal Size in the Rat via Different Mechanisms

Endocrinology ◽  
2008 ◽  
Vol 150 (3) ◽  
pp. 1174-1181 ◽  
Author(s):  
Elisabeth B. Rüttimann ◽  
Myrtha Arnold ◽  
Jacquelien J. Hillebrand ◽  
Nori Geary ◽  
Wolfgang Langhans
Keyword(s):  
Food Intake ◽  
Vena Cava ◽  
Meal Size ◽  
Dark Phase ◽  
Hepatic Portal Vein ◽  
Vagal Afferent ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Hepatic Portal ◽  
Afferent Signaling

Peripheral administration of glucagon-like peptide (GLP)-1 reduces food intake in animals and humans, but the sites and mechanism of this effect and its physiological significance are not yet clear. To investigate these issues, we prepared rats with chronic catheters and infused GLP-1 (0.2 ml/min; 2.5 or 5.0 min) during the first spontaneous dark-phase meals. Infusions were remotely triggered 2–3 min after meal onset. Hepatic portal vein (HPV) infusion of 1.0 or 3.0 (but not 0.33) nmol/kg GLP-1 reduced the size of the ongoing meal compared with vehicle without affecting the subsequent intermeal interval, the size of subsequent meals, or cumulative food intake. In double-cannulated rats, HPV and vena cava infusions of 1.0 nmol/kg GLP-1 reduced meal size similarly. HPV GLP-1 infusions of 1.0 nmol/kg GLP-1 also reduced meal size similarly in rats with subdiaphragmatic vagal deafferentations and in sham-operated rats. Finally, HPV and ip infusions of 10 nmol/kg GLP-1 reduced meal size similarly in sham-operated rats, but only HPV GLP-1 reduced meal size in subdiaphragmatic vagal deafferentation rats. These data indicate that peripherally infused GLP-1 acutely and specifically reduces the size of ongoing meals in rats and that the satiating effect of ip, but not iv, GLP-1 requires vagal afferent signaling. The findings suggest that iv GLP-1 infusions do not inhibit eating via hepatic portal or hepatic GLP-1 receptors but may act directly on the brain. Intrameal hepatic portal and intraperitoneal (IP) infusions of GLP-1 reduce meal size in rats, but only IP GLP-1 requires vagal afferent signaling for this effect.

scholarly journals Preproglucagon neurons in the hindbrain have IL-6 receptor-α and show Ca2+ influx in response to IL-6

2016 ◽  
Vol 311 (1) ◽  
pp. R115-R123 ◽  
Author(s):  
Fredrik Anesten ◽  
Marie K. Holt ◽  
Erik Schéle ◽  
Vilborg Pálsdóttir ◽  
Frank Reimann ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Food Intake ◽  
Extracellular Space ◽  
Solitary Tract ◽  
Neuronal Marker ◽  
Reporter Mice ◽  
The Central Nervous System ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Brain

Neuronal circuits in the hypothalamus and hindbrain are of importance for control of food intake, energy expenditure, and fat mass. We have recently shown that treatment with exendin-4 (Ex-4), an analog of the proglucagon-derived molecule glucagon-like peptide 1 (GLP-1), markedly increases mRNA expression of the cytokine interleukin-6 (IL-6) in the hypothalamus and hindbrain and that this increase partly mediates the suppression of food intake and body weight by Ex-4. Endogenous GLP-1 in the central nervous system (CNS) is produced by preproglucagon (PPG) neurons of the nucleus of the solitary tract (NTS) in the hindbrain. These neurons project to various parts of the brain, including the hypothalamus. Outside the brain, IL-6 stimulates GLP-1 secretion from the gut and pancreas. In this study, we aim to investigate whether IL-6 can affect GLP-1-producing PPG neurons in the nucleus of the solitary tract (NTS) in mouse hindbrain via the ligand binding part of the IL-6 receptor, IL-6 receptor-α (IL-6Rα). Using immunohistochemistry, we found that IL-6Rα was localized on PPG neurons of the NTS. Recordings of these neurons in GCaMP3/GLP-1 reporter mice showed that IL-6 enhances cytosolic Ca2+ concentration in neurons capable of expressing PPG. We also show that the Ca2+ increase originates from the extracellular space. Furthermore, we found that IL-6Rα was localized on cells in the caudal hindbrain expressing immunoreactive NeuN (a neuronal marker) or CNP:ase (an oligodendrocyte marker). In summary, IL-6Rα is present on PPG neurons in the NTS, and IL-6 can stimulate these cells by increasing influx of Ca2+ to the cytosol from the extracellular space.

scholarly journals Central infusion of GLP-1, but not leptin, produces conditioned taste aversions in rats

1997 ◽  
Vol 272 (2) ◽  
pp. R726-R730 ◽  
Author(s):  
T. E. Thiele ◽  
G. Van Dijk ◽  
L. A. Campfield ◽  
F. J. Smith ◽  
P. Burn ◽  
...  
Keyword(s):  
Side Effects ◽  
Food Intake ◽  
Consummatory Behavior ◽  
Central Administration ◽  
Short Term ◽  
Nonspecific Effects ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Ob Protein

Leptin (ob protein) and glucagon-like peptide-1-(7-36) amide (GLP-1) are peptides recently proposed to be involved in the regulation of food intake. Although the ability of exogenous leptin and GLP-1 to modulate consummatory behavior is consistent with the suggestion that these peptides are endogenous regulatory agents, central administration of these peptides may have aversive side effects, which could explain the anorexia. In the present experiment, exposure to a saccharine taste was immediately followed by central administration of leptin or GLP-1 to determine if these drugs could produce a conditioned taste aversion (CTA) in rats. At doses equated for producing comparable reductions in short-term food intake, GLP-1, but not leptin, generated a robust CTA. Although leptin caused no aversion, this peptide was the only drug to cause relatively long-term reductions in food consumption (16 h) and body weight (24 h). Hence, the results indicate that central GLP-1 produces aversive side effects, and it is argued that these nonspecific effects may explain the anorectic actions of GLP-1.

scholarly journals Potential modulation of plasma ghrelin and glucagon-like peptide-1 by anorexigenic cannabinoid compounds, SR141716A (rimonabant) and oleoylethanolamide

2004 ◽  
Vol 92 (5) ◽  
pp. 757-761 ◽  
Author(s):  
Patrice D. Cani ◽  
Maite Lasa Montoya ◽  
Audrey M. Neyrinck ◽  
Nathalie M. Delzenne ◽  
Didier M. Lambert
Keyword(s):  
Gastrointestinal Tract ◽  
Food Intake ◽  
Receptor Antagonist ◽  
Food Consumption ◽  
Cannabinoid Receptor ◽  
Short Term ◽  
Cannabinoid Compounds ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Fasted Rats

The CB1 cannabinoid receptor antagonist, N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (rimonabant; SR141716A), and oleoylethanolamide (OEA) are known to reduce food consumption, by, at least partially, a peripheral regulation of feeding. The effects of systemic SR141716A or OEA (5 mg/kg) administrations on food consumption in 24 h food-deprived and fed rats were investigated. In fasted rats, SR141716A and OEA produced an inhibition in food intake measurable the first 20 min following injection. The increase in ghrelin levels observed in the vehicle-injected rats was abolished in animals receiving OEA and significantly reduced with SR141716A. Neither OEA nor SR141716A modified glucagon-like peptide-1 (7–36) amide portal levels 20 min after the administration. In fed rats, plasma ghrelin levels of SR141716A- and OEA-treated rats were 35% lower as compared with those of the vehicle-injected rats. These results show an influence of cannabinoid agents on circulating ghrelin levels and suggest that their short-term action on appetite seems to be in accordance with the control of secretion of gastrointestinal orexigenic peptides, mainly expressed in the upper part of the gastrointestinal tract.

Central glucagon-like peptide 1 receptor-induced anorexia requires glucose metabolism-mediated suppression of AMPK and is impaired by central fructose

2013 ◽  
Vol 304 (7) ◽  
pp. E677-E685 ◽  
Author(s):  
Melissa A. Burmeister ◽  
Jennifer Ayala ◽  
Daniel J. Drucker ◽  
Julio E. Ayala
Keyword(s):  
Food Intake ◽  
Glucose Metabolism ◽  
Dependent Manner ◽  
Anorectic Effect ◽  
Dependent Inhibition ◽  
Glycolytic Inhibitor ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Amp Activated Protein Kinase ◽  
Mediated Reduction

Glucagon-like peptide-1 (GLP-1) suppresses food intake via activation of a central (i.e., brain) GLP-1 receptor (GLP-1R). Central AMP-activated protein kinase (AMPK) is a nutrient-sensitive regulator of food intake that is inhibited by anorectic signals. The anorectic effect elicited by hindbrain GLP-1R activation is attenuated by the AMPK stimulator AICAR. This suggests that central GLP-1R activation suppresses food intake via inhibition of central AMPK. The present studies examined the mechanism(s) by which central GLP-1R activation inhibits AMPK. Supporting previous findings, AICAR attenuated the anorectic effect elicited by intracerebroventricular (icv) administration of the GLP-1R agonist exendin-4 (Ex-4). We demonstrate that Ex-4 stimulates glycolysis and suppresses AMPK phosphorylation in a glucose-dependent manner in hypothalamic GT1-7 cells. This suggests that inhibition of AMPK and food intake by Ex-4 requires central glucose metabolism. Supporting this, the glycolytic inhibitor 2-deoxyglucose (2-DG) attenuated the anorectic effect of Ex-4. However, icv glucose did not enhance the suppression of food intake by Ex-4. AICAR had no effect on Ex-4-mediated reduction in locomotor activity. We also tested whether other carbohydrates affect the anorectic response to Ex-4. Intracerebroventricular pretreatment with the sucrose metabolite fructose, an AMPK activator, attenuated the anorectic effect of Ex-4. This potentially explains the increased food intake observed in sucrose-fed mice. In summary, we propose a model whereby activation of the central GLP-1R reduces food intake via glucose metabolism-dependent inhibition of central AMPK. We also suggest that fructose stimulates food intake by impairing central GLP-1R action. This has significant implications given the correlation between sugar consumption and obesity.

scholarly journals Hindbrain glucagon-like peptide-1 neurons track intake volume and contribute to injection stress-induced hypophagia in meal-entrained rats

2016 ◽  
Vol 310 (10) ◽  
pp. R906-R916 ◽  
Author(s):  
Alison D. Kreisler ◽  
Linda Rinaman
Keyword(s):  
Food Intake ◽  
Potential Role ◽  
Liquid Diet ◽  
Neural Activation ◽  
Intracerebroventricular Injection ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Diet Intake ◽  
Published Research ◽  
Diet Type

Published research supports a role for central glucagon-like peptide 1 (GLP-1) signaling in suppressing food intake in rodent species. However, it is unclear whether GLP-1 neurons track food intake and contribute to satiety, and/or whether GLP-1 signaling contributes to stress-induced hypophagia. To examine whether GLP-1 neurons track intake volume, rats were trained to consume liquid diet (LD) for 1 h daily until baseline intake stabilized. On test day, schedule-fed rats consumed unrestricted or limited volumes of LD or unrestricted volumes of diluted (calorically matched to LD) or undiluted Ensure. Rats were perfused after the test meal, and brains processed for immunolocalization of cFos and GLP-1. The large majority of GLP-1 neurons expressed cFos in rats that consumed satiating volumes, regardless of diet type, with GLP-1 activation proportional to intake volume. Since GLP-1 signaling may limit intake only when such large proportions of GLP-1 neurons are activated, a second experiment examined the effect of central GLP-1 receptor (R) antagonism on 2 h intake in schedule-fed rats. Compared with baseline, intracerebroventricular vehicle (saline) suppressed Ensure intake by ∼11%. Conversely, intracerebroventricular injection of vehicle containing GLP-1R antagonist increased intake by ∼14% compared with baseline, partly due to larger second meals. We conclude that GLP-1 neural activation effectively tracks liquid diet intake, that intracerebroventricular injection suppresses intake, and that central GLP-1 signaling contributes to this hypophagic effect. GLP-1 signaling also may contribute to satiety after large volumes have been consumed, but this potential role is difficult to separate from a role in the hypophagic response to intracerebroventricular injection.

scholarly journals The deletion of glucagon-like peptide-1 receptors expressing neurons in the dorsomedial hypothalamic nucleus disrupts the diurnal feeding pattern and induces hyperphagia and obesity

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yuko Maejima ◽  
Shoko Yokota ◽  
Masaru Shimizu ◽  
Shoichiro Horita ◽  
Daisuke Kobayashi ◽  
...  
Keyword(s):  
Nucleus Tractus Solitarius ◽  
Physiological Role ◽  
Feeding Pattern ◽  
Hypothalamic Nucleus ◽  
Acid Decarboxylase ◽  
Mrna Levels ◽  
Dorsomedial Hypothalamic Nucleus ◽  
Fos Expression ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Background Feeding rhythm disruption contributes to the development of obesity. The receptors of glucagon-like peptide-1 (GLP-1) are distributed in the wide regions of the brain. Among these regions, GLP-1 receptors (GLP-1R) are expressed in the dorsomedial hypothalamic nucleus (DMH) which are known to be associated with thermogenesis and circadian rhythm development. However, the physiological roles of GLP-1R expressing neurons in the DMH remain elusive. Methods To examine the physiological role of GLP-1R expressing neurons in the DMH, saporin-conjugated exenatide4 was injected into rat brain DMH to delete GLP-1R-positive neurons. Subsequently, locomotor activity, diurnal feeding pattern, amount of food intake and body weight were measured. Results This deletion of GLP-1R-positive neurons in the DMH induced hyperphagia, the disruption of diurnal feeding pattern, and obesity. The deletion of GLP-1R expressing neurons also reduced glutamic acid decarboxylase 67 and cholecystokinin A receptor mRNA levels in the DMH. Also, it reduced the c-fos expression after refeeding in the suprachiasmatic nucleus (SCN). Thirty percent of DMH neurons projecting to the SCN expressed GLP-1R. Functionally, refeeding after fasting induced c-fos expression in the SCN projecting neurons in the DMH. As for the projection to the DMH, neurons in the nucleus tractus solitarius (NTS) were found to be projecting to the DMH, with 33% of those neurons being GLP-1-positive. Refeeding induced c-fos expression in the DMH projecting neurons in the NTS. Conclusion These findings suggest that GLP-1R expressing neurons in the DMH may mediate feeding termination. In addition, this meal signal may be transmitted to SCN neurons and change the neural activities.

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