scholarly journals Anorexigenic effect of cholecystokinin is lost but that of CART (Cocaine and Amphetamine Regulated Transcript) peptide is preserved in monosodium glutamate obese mice

2009 ◽  
pp. 717-723 ◽  
Author(s):  
B Železná ◽  
J Maixnerová ◽  
R Matyšková ◽  
R Haugvicová ◽  
D Blokešová ◽  
...  
Keyword(s):  
Food Intake ◽  
Arcuate Nucleus ◽  
Monosodium Glutamate ◽  
Central Administration ◽  
Obese Mice ◽  
Male Mice ◽  
Short Term ◽  
Leptin Signaling ◽  
Cart Peptide ◽  
Anorexigenic Effect

Monosodium glutamate (MSG) treatment of neonatal mice results in a selective damage to the arcuate nucleus (ARC) and development of obesity with increased adiposity at sustained body weight in the adulthood. Feeding pattern of the MSG obese mice is unusual. Our previous results showed that after 24-h fasting, MSG mice consumed negligible amount of food in several hours and therefore, it was impossible to register the effect of peptides attenuating food intake such as cholecystokinin (CCK) or cocaine- and amphetamine-regulated transcript (CART) peptide. To overcome this problem, two findings were used: firstly, orexigenic effect of neuropeptide Y (NPY) was attenuated both by CCK or CART peptide in lean fed mice and secondly, orexigenic effect of NPY was preserved in fed rats with MSG obesity. In this study, short-term food intake in fed lean and MSG obese C57BL/6 male mice was measured after simultaneous central administration of orexigenic NPY with either CART peptide or peripherally administered CCK. Anorexigenic action of exogenous CART peptide was preserved in MSG obese mice. On the other hand, satiety effect of exogenous CCK was completely lost in MSG obese mice. In conclusion, effective leptin signaling in ARC is necessary for satiety effect of CCK.

Topiramate Treatment Improves Hypothalamic Insulin and Leptin Signaling and Action and Reduces Obesity in Mice

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4401-4411 ◽  
Author(s):  
Andrea M. Caricilli ◽  
Erica Penteado ◽  
Lélia L. de Abreu ◽  
Paula G. F. Quaresma ◽  
Andressa C. Santos ◽  
...  
Keyword(s):  
Food Intake ◽  
Molecular Mechanisms ◽  
Janus Kinase ◽  
Mrna Levels ◽  
Obese Mice ◽  
Short Term ◽  
Short Term Treatment ◽  
Peripheral Tissues ◽  
Leptin Signaling ◽  
Brown Adipose

Topiramate (TPM) treatment has been shown to reduce adiposity in humans and rodents. The reduction in adiposity is related to decreased food intake and increased energy expenditure. However, the molecular mechanisms through which TPM induces weight loss are contradictory and remain to be clarified. Whether TPM treatment alters hypothalamic insulin, or leptin signaling and action, is not well established. Thus, we investigate herein whether short-term TPM treatment alters energy balance by affecting insulin and leptin signaling, action, or neuropeptide expression in the hypothalamus of mice fed with a high-fat diet. As expected, short-term treatment with TPM diminished adiposity in obese mice mainly due to reduced food intake. TPM increased anorexigenic signaling by enhancing the leptin-induced leptin receptor/Janus kinase 2/signal transducer and activator of transcription 3 pathway and the insulin-induced insulin receptor substrate/Akt/forkhead box O1 pathway in parallel to reduced phosphatase protein expression in the hypothalamus of obese mice. These effects were independent of body weight. TPM also raised anorexigenic neuropeptides such as POMC, TRH, and CRH mRNA levels in obese mice. In addition, TPM increased the activation of the hypothalamic MAPK/ERK pathway induced by leptin, accompanied by an increase in peroxisome proliferator-activated receptor-coactivator α and uncoupling protein 1 protein levels in brown adipose tissue. Furthermore, TPM increased AMP-activated protein kinase and acetyl-coenzyme A carboxylase phosphorylation in peripheral tissues, which may help improve energy metabolism in these tissues. Together, these results provide novel insights into the molecular mechanisms through which TPM treatment reduces adiposity.

Lateral ventricular ghrelin and fourth ventricular ghrelin induce similar increases in food intake and patterns of hypothalamic gene expression

2006 ◽  
Vol 290 (6) ◽  
pp. R1565-R1569 ◽  
Author(s):  
Kimberly P. Kinzig ◽  
Karen A. Scott ◽  
Jayson Hyun ◽  
Sheng Bi ◽  
Timothy H. Moran
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Fourth Ventricle ◽  
Time Course ◽  
Arcuate Nucleus ◽  
Central Administration ◽  
Stimulatory Action ◽  
Hypothalamic Arcuate Nucleus ◽  
Ghrelin Receptors ◽  
The Brain

The gut peptide ghrelin has been shown to stimulate food intake after both peripheral and central administration, and the hypothalamic arcuate nucleus has been proposed to be the major site for mediating this feeding stimulatory action. Ghrelin receptors are widely distributed in the brain, and hindbrain ghrelin administration has been shown to potently stimulate feeding, suggesting that there may be other sites for ghrelin action. In the present study, we have further assessed potential sites for ghrelin action by comparing the ability of lateral and fourth ventricular ghrelin administration to stimulate food intake and alter patterns of hypothalamic gene expression. Ghrelin (0.32, 1, or 3.2 nmol) in the lateral or fourth ventricle significantly increased food intake in the first 4 h after injection, with no ventricle-dependent differences in degree or time course of hyperphagia. One nanomole of ghrelin into either the lateral or fourth ventricle resulted in similar increases in arcuate nucleus neuropeptide Y mRNA expression. Expression levels of agouti-related peptide or proopiomelanocortin mRNA were not affected by ghrelin administration. These data demonstrate that ghrelin can affect food intake and hypothalamic gene expression through interactions at multiple brain sites.

scholarly journals Oxytocin Administration Alleviates Acute but Not Chronic Leptin Resistance of Diet-Induced Obese Mice

2018 ◽  
Vol 20 (1) ◽  
pp. 88 ◽  
Author(s):  
Mehdi Labyb ◽  
Chloé Chrétien ◽  
Aurélie Caillon ◽  
Françoise Rohner-Jeanrenaud ◽  
Jordi Altirriba
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Body Weight Gain ◽  
Leptin Resistance ◽  
Obese Mice ◽  
Short Term ◽  
Continuous Administration ◽  
Pre Treatment ◽  
Treatment Of Obesity

Whereas leptin administration only has a negligible effect on the treatment of obesity, it has been demonstrated that its action can be improved by co-administration of leptin and one of its sensitizers. Considering that oxytocin treatment decreases body weight in obese animals and humans, we investigated the effects of oxytocin and leptin cotreatment. First, lean and diet-induced obese (DIO) mice were treated with oxytocin for 2 weeks and we measured the acute leptin response. Second, DIO mice were treated for 2 weeks with saline, oxytocin (50 μg/day), leptin (20 or 40 µg/day) or oxytocin plus leptin. Oxytocin pre-treatment restored a normal acute leptin response, decreasing food intake and body weight gain. Chronic continuous administration of oxytocin or leptin at 40 µg/day decreased body weight in the presence (leptin) or in the absence (oxytocin) of cumulative differences in food intake. Saline or leptin treatment at 20 µg/day had no impact on body weight. Oxytocin and leptin cotreatments had no additional effects compared with single treatments. These results point to the fact that chronic oxytocin treatment improves the acute, but not the chronic leptin response, suggesting that this treatment could be used to improve the short-term satiety effect of leptin.

scholarly journals Influence of restricting the diet on breeding in genetically obese mice

1972 ◽  
Vol 6 (1) ◽  
pp. 9-18 ◽  
Author(s):  
A. Eastcott
Keyword(s):  
Food Intake ◽  
Optimal Conditions ◽  
Obese Mice ◽  
Male Mice ◽  
Restricted Diet ◽  
The Mean ◽  
Set Up ◽  
Mean Time ◽  
Obese Male

A system for breeding from obese male mice ( ob/ob) by restricting food intake is described. It is shown that a 40% reduction in food intake at 6½-8½ weeks of age is optimal in the colony under review. Males on restricted diet did not mate immediately but went through a period of adaptation; the mean time before vaginal plugs were observed was 30 days. Subsequent vaginal plugs occurred on average every 17 days and 69% of these matings resulted in litters. Under optimal conditions over 90% of all obese males set up on restricted diets mated and sired young.

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 C1q/TNF-related protein 4 restores leptin sensitivity by downregulating NF-κB signaling and microglial activation

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Liu Ye ◽  
Gongwei Jia ◽  
Yuejie Li ◽  
Ying Wang ◽  
Hong Chen ◽  
...  
Keyword(s):  
Food Intake ◽  
Microglial Activation ◽  
Obese Mice ◽  
Related Protein ◽  
Leptin Signaling ◽  
Leptin Sensitivity ◽  
Tnf Α ◽  
Hypothalamic Inflammation ◽  
The Impact

Abstract Objective C1qTNF-related protein 4 (CTRP4) acts in the hypothalamus to modulate food intake in diet-induced obese mice and has been shown to exert an anti-inflammatory effect on macrophages. Since high-fat diet-induced microglial activation and hypothalamic inflammation impair leptin signaling and increase food intake, we aimed to explore the potential connection between the anorexigenic effect of CTRP4 and the suppression of hypothalamic inflammation in mice with DIO. Methods Using an adenovirus-mediated hypothalamic CTRP4 overexpression model, we investigated the impact of CTRP4 on food intake and the hypothalamic leptin signaling pathway in diet-induced obese mice. Furthermore, central and plasma proinflammatory cytokines, including TNF-α and IL-6, were measured by Western blotting and ELISA. Changes in the hypothalamic NF-κB signaling cascade and microglial activation were also examined in vivo. In addition, NF-κB signaling and proinflammatory factors were investigated in BV-2 cells after CTRP4 intervention. Results We found that food intake was decreased, while leptin signaling was significantly improved in mice with DIO after CTRP4 overexpression. Central and peripheral TNF-α and IL-6 levels were reduced by central Ad-CTRP4 administration. Hypothalamic NF-κB signaling and microglial activation were also significantly suppressed in vivo. In addition, NF-κB signaling was inhibited in BV-2 cells following CTRP4 intervention, which was consistent with the decreased production of TNF-α and IL-6. Conclusions Our data indicate that CTRP4 reverses leptin resistance by inhibiting NF-κB-dependent microglial activation and hypothalamic inflammation.

scholarly journals Endogenous Melanocortin Antagonist in Fish: Structure, Brain Mapping, and Regulation by Fasting of the Goldfish Agouti-Related Protein Gene

Endocrinology ◽  
2003 ◽  
Vol 144 (10) ◽  
pp. 4552-4561 ◽  
Author(s):  
José Miguel Cerdá-Reverter ◽  
Richard Ector Peter
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Brain Mapping ◽  
Arcuate Nucleus ◽  
Mrna Levels ◽  
Central Administration ◽  
Related Protein ◽  
Melanocortin Peptides ◽  
Agouti Related Protein ◽  
Tuberal Nucleus

Agouti-related protein (AGRP) is a naturally occurring antagonist of melanocortin. In mammals, central AGRP expression is restricted to the arcuate nucleus in which it plays a key role in the control of energy balance by antagonizing melanocortin effects at melanocortin 4 receptors. In goldfish, melanocortin 4 receptor is profusely expressed within the main brain areas for the control of energy balance, and central administration of agonist or antagonist analogs inhibits or stimulates food intake, respectively. Here we demonstrate that the goldfish genome has a homologous gene to mammalian AGRP. Detailed brain mapping by in situ hybridization shows that AGRP is exclusively expressed in the ventrobasal hypothalamic lateral tuberal nucleus, the teleostean homolog of the arcuate nucleus. Fasting up-regulates its mRNA levels in the lateral tuberal nucleus. In the periphery, AGRP is expressed in several tissues including ovary, muscle, and ventral skin, suggesting that AGRP might regulate peripheral actions of melanocortin peptides. The results provide the first evidence for an endogenous melanocortin antagonist in nontetrapod species and suggest that hypothalamic overexpression during fasting might regulate the inhibitory effects of melanocortin peptides on food intake in goldfish.

GLP-1 regulates the POMC neurons of the arcuate nucleus both directly and indirectly via presynaptic action

2020 ◽  
Author(s):  
Zoltán Péterfi ◽  
Anett Szilvásy-Szabó ◽  
Erzsébet Farkas ◽  
Yvette Ruska ◽  
Charles Pyke ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Firing Rate ◽  
G Protein ◽  
Arcuate Nucleus ◽  
Male Mice ◽  
Excitatory Effect ◽  
Axon Terminals ◽  
Postsynaptic Currents ◽  
Electrophysiological Studies ◽  
Anorexigenic Effect

GLP-1 exerts its anorexigenic effect at least partly via the POMC neurons of the arcuate nucleus (ARC). These neurons are known to express GLP-1 receptor (GLP-1R). To determine whether in addition to its direct effect, GLP-1 also modulates, how neuronal inputs can regulate the POMC neurons by acting on presynaptic terminals, ultrastructural and electrophysiological studies were performed on tissues of adult male mice. GLP-1R-immunoreactivity was associated with the cell membrane of POMC neurons and with axon terminals forming synapses on these cells. The GLP-1 analog Exendin 4 (Ex4) markedly increased the firing rate of all examined POMC neurons and depolarized these cells. These effects of Ex4 were prevented by intracellular administration of the G-protein blocker GDP-β-S. Ex4 also influenced the miniature and evoked postsynaptic currents (PSCs) of POMC neurons. Ex4 increased the frequency of miniature excitatory PSCs and the amplitude of the evoked excitatory PSCs in half of the POMC neurons. Ex4 increased the frequency of miniature inhibitory PSCs and the amplitudes of the evoked inhibitory PSCs in one-third of neurons. These effects of Ex4 were not influenced by intracellular GDP-β-S, indicating that GLP-1-signaling directly stimulates a population of axon terminals innervating the POMC neurons. The different Ex4 responsiveness of their mPSCs indicates the heterogeneity of the POMC neurons of the ARC. In summary, our data demonstrate that in addition to its direct excitatory effect on the POMC neurons, GLP-1-signaling also facilitates the presynaptic input of these cells by acting on presynaptically localized GLP-1R.

scholarly journals Leptin Signaling in the Arcuate Nucleus Reduces Insulin’s Capacity to Suppress Hepatic Glucose Production in Obese Mice

Cell Reports ◽  
2019 ◽  
Vol 26 (2) ◽  
pp. 346-355.e3 ◽  
Author(s):  
Eglantine Balland ◽  
Weiyi Chen ◽  
Garron T. Dodd ◽  
Gregory Conductier ◽  
Roberto Coppari ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Obese Mice ◽  
Leptin Signaling ◽  
Hepatic Glucose

Persistent Leptin Signaling in the Arcuate Nucleus Impairs Hypothalamic Insulin Signaling and Glucose Homeostasis in Obese Mice

2019 ◽  
Vol 109 (4) ◽  
pp. 374-390 ◽  
Author(s):  
Eglantine Balland ◽  
Weiyi Chen ◽  
Tony Tiganis ◽  
Michael A. Cowley
Keyword(s):  
Glucose Homeostasis ◽  
Insulin Signaling ◽  
Arcuate Nucleus ◽  
Leptin Receptor ◽  
Inhibitory Effect ◽  
Obese Mice ◽  
Leptin Signaling ◽  
Insulin Tolerance ◽  
Hormonal Resistance ◽  
Receptor Neurons

Background: Obesity is associated with reduced physiological responses to leptin and insulin, leading to the concept of obesity-associated hormonal resistance. Objectives: Here, we demonstrate that contrary to expectations, leptin signaling not only remains functional but also is constantly activated in the arcuate nucleus of the hypothalamus (ARH) neurons of obese mice. This state of persistent response to endogenous leptin underpins the lack of response to exogenous leptin. Methods and Results: The study of combined leptin and insulin signaling demonstrates that there is a common pool of ARH neurons responding to both hormones. More importantly, we show that the constant activation of leptin receptor neurons in the ARH prevents insulin signaling in these neurons, leading to impaired glucose tolerance. Accordingly, antagonising leptin signaling in diet-induced obese (DIO) mice restores insulin signaling in the ARH and improves glucose homeostasis. Direct inhibition of PTP1B in the CNS restores arcuate insulin signaling similarly to leptin inhibition; this effect is likely to be mediated by AgRP neurons since PTP1B deletion specifically in AgRP neurons restores glucose and insulin tolerance in DIO mice. Conclusions: Finally, our results suggest that the constant activation of arcuate leptin signaling in DIO mice increases PTP1B expression, which exerts an inhibitory effect on insulin signaling leading to impaired glucose homeostasis.

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