Coinjection of CCK and leptin reduces food intake via increased CART/TRH and reduced AMPK phosphorylation in the hypothalamus

2014 ◽  
Vol 306 (11) ◽  
pp. E1284-E1291 ◽  
Author(s):  
Sayaka Akieda-Asai ◽  
Paul-Emile Poleni ◽  
Yukari Date
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Interactive Effect ◽  
Reduce Food Intake ◽  
Mrna Levels ◽  
Neural Pathway ◽  
Ampk Phosphorylation ◽  
Amp Activated Protein Kinase ◽  
Insight Into

CCK and leptin are anorectic hormones produced in the small intestine and white adipose tissue, respectively. Investigating how these hormones act together as an integrated anorectic signal is important for elucidating the mechanisms by which energy balance is maintained. We found here that coadministration of subthreshold CCK and leptin, which individually have no effect on feeding, dramatically reduced food intake in rats. Phosphorylation of AMP-activated protein kinase (AMPK) in the hypothalamus significantly decreased after coinjection of CCK and leptin. In addition, coadministration of these hormones significantly increased mRNA levels of anorectic cocaine- and amphetamine-regulated transcript (CART) and thyrotropin-releasing hormone (TRH) in the hypothalamus. The interactive effect of CCK and leptin on food intake was abolished by intracerebroventricular preadministration of the AMPK activator AICAR or anti-CART/anti-TRH antibodies. These findings indicate that coinjection of CCK and leptin reduces food intake via reduced AMPK phosphorylation and increased CART/TRH in the hypothalamus. Furthermore, by using midbrain-transected rats, we investigated the role of the neural pathway from the hindbrain to the hypothalamus in the interaction of CCK and leptin to reduce food intake. Food intake reduction induced by coinjection of CCK and leptin was blocked in midbrain-transected rats. Therefore, the neural pathway from hindbrain to hypothalamus plays an important role in transmitting the anorectic signals provided by coinjection of CCK and leptin. Our findings give further insight into the mechanisms of feeding and energy balance.

Energy balance and food intake: The role of PPARγ gene polymorphisms

2006 ◽  
Vol 88 (3) ◽  
pp. 227-233 ◽  
Author(s):  
Joanne E. Cecil ◽  
Peter Watt ◽  
Colin N. Palmer ◽  
Marion Hetherington
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Gene Polymorphisms ◽  
Pparγ Gene

scholarly journals The role of RFamide peptides in feeding

2007 ◽  
Vol 192 (1) ◽  
pp. 3-15 ◽  
Author(s):  
David A Bechtold ◽  
Simon M Luckman
Keyword(s):  
Biological Activity ◽  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Feeding Behaviour ◽  
Animal Kingdom ◽  
Primary Function

In the three decades since FMRFamide was isolated from the clam Macrocallista nimbosa, the list of RFamide peptides has been steadily growing. These peptides occur widely across the animal kingdom, including five groups of RFamide peptides identified in mammals. Although there is tremendous diversity in structure and biological activity in the RFamides, the involvement of these peptides in the regulation of energy balance and feeding behaviour appears consistently through evolution. Even so, questions remain as to whether feeding-related actions represent a primary function of the RFamides, especially within mammals. However, as we will discuss here, the study of RFamide function is rapidly expanding and with it so is our understanding of how these peptides can influence food intake directly as well as related aspects of feeding behaviour and energy expenditure.

Antagonism of opioid receptors reduces body fat in obese rats by decreasing food intake and stimulating lipid utilization

2003 ◽  
Vol 284 (6) ◽  
pp. R1399-R1408 ◽  
Author(s):  
Michael A. Statnick ◽  
Frank C. Tinsley ◽  
Brian J. Eastwood ◽  
Todd M. Suter ◽  
Charles H. Mitch ◽  
...  
Keyword(s):  
Body Composition ◽  
Energy Balance ◽  
Food Intake ◽  
Energy Intake ◽  
Opioid Receptors ◽  
Oral Treatment ◽  
Positive Energy ◽  
Reduce Food Intake ◽  
Tissue Mass ◽  
Obese Rats

Agonists to opioid receptors induce a positive energy balance, whereas antagonists at these receptors reduce food intake and body weight in rodent models of obesity. An analog of 3,4-dimethyl-4-(3-hydroxyphenyl)piperidine, LY255582, is a potent non-morphinan antagonist for μ-, κ-, and δ-receptors ( K i of 0.4, 2.0, and 5.2 nM, respectively). In the present study, we examined the effects of oral LY255582 treatment on caloric intake, calorie expenditure, and body composition in dietary-induced obese rats. Acute oral treatment of LY255582 produced a dose-dependent decrease in energy intake and respiratory quotient (RQ), which correlated with the occupancy of central opioid receptors. Animals receiving chronic oral treatment with LY255582 for 14 days maintained a negative energy balance that was sustained by increased lipid use. Analysis of body composition revealed a reduction in fat mass accretion, with no change in lean body mass, in animals treated with LY255582. Therefore, chronic treatment with LY255582 reduces adipose tissue mass by reducing energy intake and stimulating lipid use.

Hypothalamic AMP-activated Protein Kinase as a Regulator of Food Intake and Energy Balance

2016 ◽  
Vol 15 (8) ◽  
pp. 896-909 ◽  
Author(s):  
Tae Seok Oh ◽  
Yoonjeong Jeon ◽  
Seolsong Kim ◽  
Eun-Kyoung Kim
Keyword(s):  
Energy Balance ◽  
Protein Kinase ◽  
Food Intake ◽  
Amp Activated Protein Kinase

Abstract 5559: Role of AMP-activated Protein Kinase in Ischemia-Reperfusion-Induced Barrier Failure in Endothelial Monolayers

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Muhammad Assad ◽  
Muhammad Arshad ◽  
Frauke V Haertel ◽  
Muhammad Aslam ◽  
Ingrid Fleming ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Barrier Function ◽  
Ischemia Reperfusion ◽  
Fold Increase ◽  
Gap Formation ◽  
Endothelial Monolayers ◽  
Ampk Phosphorylation ◽  
Barrier Failure ◽  
Amp Activated Protein Kinase

Background: Ischemia-reperfusion provokes endothelial barrier dysfunction leading to edema formation and organ failure. The AMP-activated protein kinase (AMPK) is a fuel sensor which becomes activated under ischemia. It is now apparent that AMPK may also play important roles in stabilization of cell-adhesion. Here, it is hypothesized that AMPK may play an important role in protection barrier function under metabolic stress. Methods and Results: Overexpression of a dominant negative AMPK mutant in endothelial monolayers from human umbilical veins (EC) caused a 2-fold increase in basal permeability (albumin flux across the monolayers). In accordance, downregulation of AMPK by siRNA (~60%) leads to gap formation between adjacent EC, disintegration of cell adhesion structures and alterations of the cytoskeleton (loss of VE-cadherin at cell borders, actin stress fiber formation; immunocytochemistry), indicating that AMPK plays an important role in maintenance of barrier integrity. To analyse the role of AMPK on barrier function EC were exposed to ischemia (40 min, Po 2 <5 mm Hg; pH 6.4) followed by reperfusion (40 min, Po 2 =140 mm Hg; pH 7.4). Ischemia caused an immediate increase in permeability (gap formation, video-imaging technique) and a 3-fold increase in AMPK activity (AMPK phosphorylation; western blot) after 40 min. During reperfusion gap formation was further increased by 307± 9 % (P<0.05, n=5) within the ongoing 40 min. In contrast, AMPK phosphorylation rapidly declined to basal level within the first 10 minutes of reperfusion. However, addition of AICAR (AMPK activator; 5-aminoimidizole-4-carboxamide riboside), at the onset of reperfusion caused a rapid increase in AMPK phosphorylation and abolished the reperfusion-induced gap formation. Pretreatment of the cells with AICAR before the onset of ischemia reduced reperfusion-induced gap formation by 50 %. Conclusion: AMPK is involved in maintenance of cell-cell contacts and stabilization of basal barrier function. Pharmacological activation of AMPK within the first minutes of reperfusion can prevent hyperpermeability induced by reperfusion stress. Hence, activation of AMPK may provide a new therapeutic option to prevent ischemia-reperfusion barrier failure.

Hypophagic effects of insulin are mediated via NPY1/NPY2 receptors in broiler cockerels

2018 ◽  
Vol 96 (12) ◽  
pp. 1301-1307 ◽  
Author(s):  
Shiba Yousefvand ◽  
Farshid Hamidi ◽  
Morteza Zendehdel ◽  
Abbas Parham
Keyword(s):  
Blood Glucose ◽  
Energy Balance ◽  
Food Intake ◽  
Control Group ◽  
Control Solution ◽  
Treatment Groups ◽  
Insulin Control ◽  
And Control ◽  
Npy Receptors

Neuropeptide Y (NPY) plays a mediatory role in cerebral insulin function by maintaining energy balance. The current study was designed to determine the role of insulin in food intake and its interaction with NPY receptors in 8 experiments using broiler cockerels (4 treatment groups per experiment, except for experiment 8). Chicks received control solution or 2.5, 5, or 10 ng of insulin in experiment 1 and control solution or 1.25, 2.5, or 5 μg of receptor antagonists B5063, SF22, or SML0891 in experiments 2, 3, and 4 through intracerebroventricular (ICV) injection, respectively. In experiments 5, 6, and 7, chicks received ICV injection of B5063, SF22, SML0891, or co-injection of an antagonist + insulin, control solution, and insulin. In experiment 8, blood glucose was measured. Insulin, B5063, and SML0891 decreased food intake, while SF22 led to an increase in food intake. The hypophagic effect of insulin was also reinforced by injection of B560, but ICV injection of SF22 destroyed this hypophagic effect of insulin and increased food intake (p < 0.05). However, SML0891 had no effect on decreased food intake induced by insulin (p > 0.05). At 30 min postinjection, blood sugar in the control group was higher than that in the insulin group (p < 0.05). Therefore, the NPY1 and NPY2 receptors mediate the hypophagic effect of insulin in broiler cockerels.

scholarly journals Role of the neural pathway from hindbrain to hypothalamus in interaction of GLP1 and leptin in rats

2013 ◽  
Vol 220 (2) ◽  
pp. 109-116 ◽  
Author(s):  
Sayaka Akieda-Asai ◽  
Paul-Emile Poleni ◽  
Kazuya Hasegawa ◽  
Yukari Date
Keyword(s):  
Food Intake ◽  
Neural Pathway ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP1) and leptin are anorectic hormones. Previously, we have shown that i.p. coadministration of subthreshold GLP1 with leptin dramatically reduced food intake in rats. In this study, by using midbrain-transected rats, we investigated the role of the neural pathway from the hindbrain to the hypothalamus in the interaction of GLP1 and leptin in reducing food intake. Food intake reduction induced by coinjection of GLP1 and leptin was blocked in midbrain-transected rats. These findings indicate that the ascending neural pathway from the hindbrain plays an important role in transmitting the anorectic signals provided by coinjection of GLP1 and leptin.

scholarly journals Central Nesfatin-1 Reduces Dark-Phase Food Intake and Gastric Emptying in Rats: Differential Role of Corticotropin-Releasing Factor2 Receptor

Endocrinology ◽  
2009 ◽  
Vol 150 (11) ◽  
pp. 4911-4919 ◽  
Author(s):  
Andreas Stengel ◽  
Miriam Goebel ◽  
Lixin Wang ◽  
Jean Rivier ◽  
Peter Kobelt ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Nucleus Tractus Solitarius ◽  
Hypothalamic Nucleus ◽  
Reduce Food Intake ◽  
Dark Phase ◽  
Crf2 Receptor ◽  
Brain Ventricle ◽  
Dose Dependent

Nesfatin-1, derived from nucleobindin2, is expressed in the hypothalamus and reported in one study to reduce food intake (FI) in rats. To characterize the central anorexigenic action of nesfatin-1 and whether gastric emptying (GE) is altered, we injected nesfatin-1 into the lateral brain ventricle (intracerebroventricular, icv) or fourth ventricle (4v) in chronically cannulated rats or into the cisterna magna (intracisternal, ic) under short anesthesia and compared with ip injection. Nesfatin-1 (0.05 μg/rat, icv) decreased 2–3 h and 3–6 h dark-phase FI by 87 and 45%, respectively, whereas ip administration (2 μg/rat) had no effect. The corticotropin-releasing factor (CRF)1/CRF2 antagonist astressin-B or the CRF2 antagonist astressin2-B abolished icv nesfatin-1’s anorexigenic action, whereas an astressin2-B analog, devoid of CRF-receptor binding affinity, did not. Nesfatin-1 icv induced a dose-dependent reduction of GE by 26 and 43% that was not modified by icv astressin2-B. Nesfatin-1 into the 4v (0.05 μg/rat) or ic (0.5 μg/rat) decreased cumulative dark-phase FI by 29 and 60% at 1 h and by 41 and 37% between 3 and 5 h, respectively. This effect was neither altered by ic astressin2-B nor associated with changes in GE. Cholecystokinin (ip) induced Fos expression in 43% of nesfatin-1 neurons in the paraventricular hypothalamic nucleus and 24% of those in the nucleus tractus solitarius. These data indicate that nesfatin-1 acts centrally to reduce dark phase FI through CRF2-receptor-dependent pathways after forebrain injection and CRF2-receptor-independent pathways after hindbrain injection. Activation of nesfatin-1 neurons by cholecystokinin at sites regulating food intake may suggest a role in gut peptide satiation effect.

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.

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