scholarly journals Peripheral and central signals in the control of eating in normal, obese and binge-eating human subjects

2004 ◽  
Vol 92 (S1) ◽  
pp. S47-S57 ◽  
Author(s):  
Per M. Hellström ◽  
Allan Geliebter ◽  
Erik Näslund ◽  
Peter T. Schmidt ◽  
Eric K. Yahav ◽  
...  
Keyword(s):  
Binge Eating ◽  
Human Subjects ◽  
Present Review ◽  
Positive Energy ◽  
Appetite Control ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Gastric Capacity ◽  
The Brain ◽  
Stimulating Hormone

The worldwide increase in the incidence of obesity is a consequence of a positive energy balance, with energy intake exceeding expenditure. The signalling systems that underlie appetite control are complex, and the present review highlights our current understanding of key components of these systems. The pattern of eating in obesity ranges from over-eating associated with binge-eating disorder to the absence of binge-eating. The present review also examines evidence of defects in signalling that differentiate these sub-types. The signalling network underlying hunger, satiety and metabolic status includes the hormonal signals leptin and insulin from energy stores, and cholecystokinin, glucagon-like peptide-1, ghrelin and peptide YY3-36 from the gastrointestinal tract, as well as neuronal influences via the vagus nerve from the digestive tract. This information is routed to specific nuclei of the hypothalamus and brain stem, such as the arcuate nucleus and the solitary tract nucleus respectively, which in turn activate distinct neuronal networks. Of the numerous neuropeptides in the brain, neuropeptide Y, agouti gene-related peptide and orexin stimulate appetite, while melanocortins and α-melanocortin-stimulating hormone are involved in satiety. Of the many gastrointestinal peptides, ghrelin is the only appetite-stimulating hormone, whereas cholecystokinin, glucagon-like peptide-1 and peptide YY3-36 promote satiety. Adipose tissue provides signals about energy storage levels to the brain through leptin, adiponectin and resistin. Binge-eating has been related to a dysfunction in the ghrelin signalling system. Moreover, changes in gastric capacity are observed, and as gastric capacity is increased, so satiety signals arising from gastric and post-gastric cues are reduced. Understanding the host of neuropeptides and peptide hormones through which hunger and satiety operate should lead to novel therapeutic approaches for obesity; potential therapeutic strategies are highlighted.

scholarly journals Failure of the Brain Glucagon-Like Peptide-1-Mediated Control of Intestinal Redox Homeostasis in a Rat Model of Sporadic Alzheimer’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1118
Author(s):  
Jan Homolak ◽  
Ana Babic Perhoc ◽  
Ana Knezovic ◽  
Jelena Osmanovic Barilar ◽  
Melita Salkovic-Petrisic
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rat Model ◽  
Redox Homeostasis ◽  
Brain State ◽  
Gastrointestinal Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Brain

The gastrointestinal system may be involved in the etiopathogenesis of the insulin-resistant brain state (IRBS) and Alzheimer’s disease (AD). Gastrointestinal hormone glucagon-like peptide-1 (GLP-1) is being explored as a potential therapy as activation of brain GLP-1 receptors (GLP-1R) exerts neuroprotection and controls peripheral metabolism. Intracerebroventricular administration of streptozotocin (STZ-icv) is used to model IRBS and GLP-1 dyshomeostasis seems to be involved in the development of neuropathological changes. The aim was to explore (i) gastrointestinal homeostasis in the STZ-icv model (ii) assess whether the brain GLP-1 is involved in the regulation of gastrointestinal redox homeostasis and (iii) analyze whether brain-gut GLP-1 axis is functional in the STZ-icv animals. Acute intracerebroventricular treatment with exendin-3(9-39)amide was used for pharmacological inhibition of brain GLP-1R in the control and STZ-icv rats, and oxidative stress was assessed in plasma, duodenum and ileum. Acute inhibition of brain GLP-1R increased plasma oxidative stress. TBARS were increased, and low molecular weight thiols (LMWT), protein sulfhydryls (SH), and superoxide dismutase (SOD) were decreased in the duodenum, but not in the ileum of the controls. In the STZ-icv, TBARS and CAT were increased, LMWT and SH were decreased at baseline, and no further increment of oxidative stress was observed upon central GLP-1R inhibition. The presented results indicate that (i) oxidative stress is increased in the duodenum of the STZ-icv rat model of AD, (ii) brain GLP-1R signaling is involved in systemic redox regulation, (iii) brain-gut GLP-1 axis regulates duodenal, but not ileal redox homeostasis, and iv) brain-gut GLP-1 axis is dysfunctional in the STZ-icv model.

scholarly journals PET evaluation of light-induced modulation of microglial activation and GLP-1R expression in depressive rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Liu ◽  
Lizhen Wang ◽  
Donghui Pan ◽  
Mingzhu Li ◽  
Yaoqi Li ◽  
...  
Keyword(s):  
Microglial Activation ◽  
Light Therapy ◽  
Emission Tomography ◽  
Noninvasive Evaluation ◽  
Mild Stress ◽  
Positron Emission ◽  
Therapeutic Choice ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Brain

AbstractLight therapy has been accepted as a promising therapeutic choice for depression. Positron emission tomography (PET) combined with specific radiotracers has great benefits for revealing pathogenesis and developing therapeutics. This study aimed to investigate the influences of light therapy on microglial activation and glucagon-like peptide-1 receptor (GLP-1R) expression in the brain of depressive rats using [18F]DPA-714 and [18F]exendin-4 PET. The results showed that chronic unpredictable mild stress (CUMS)-induced depressive rats had poorer performance in behavioral tests compared to normal rats (p < 0.05) and the depressive-like behavior could be ameliorated by light therapy. Besides, depressive rats had significantly higher [18F]DPA-714 uptake and lower [18F]FDG uptake compare to normal rats in 11 and 9 regions of interest (ROIs) of the brain, respectively (p < 0.05). After 5 weeks of light therapy, higher [18F]FDG and [18F]exendin-4 uptake was observed in most ROIs of light therapy-treated depressive rats compared to untreated depressive rats (p < 0.05) and no significant differences existed in [18F]DPA-714 uptake between the two groups. This study demonstrated that light therapy can ameliorate depressive-like behavior, improve glucose metabolism, and halt the decline of brain GLP-1R expression of depressive rats, but have no effects on microglial activation caused by CUMS. Besides, this study validated that [18F]DPA-714 and [18F]exendin-4 PET have the potential for noninvasive evaluation of microglial activation and GLP-1R expression in the brain of depression.

scholarly journals Glucagon-Like Peptide 1 in the Brain: Where Is It Coming From, Where Is It Going?

Diabetes ◽  
2018 ◽  
Vol 68 (1) ◽  
pp. 15-17 ◽  
Author(s):  
Derek Daniels ◽  
Elizabeth G. Mietlicki-Baase
Keyword(s):  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Brain

Differences in the Postprandial Release of Appetite-Related Hormones Between Active and Inactive Men

2018 ◽  
Vol 28 (6) ◽  
pp. 602-610
Author(s):  
Linn Bøhler ◽  
Sílvia Ribeiro Coutinho ◽  
Jens F. Rehfeld ◽  
Linda Morgan ◽  
Catia Martins
Keyword(s):  
Plasma Concentration ◽  
Peptide Yy ◽  
Plasma Concentrations ◽  
Random Order ◽  
High Energy ◽  
Low Energy ◽  
Adult Males ◽  
Appetite Control ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Active, as opposed to inactive, individuals are able to adjust their energy intake after preloads of different energy contents. The mechanisms responsible for this remain unknown. This study examined differences in plasma concentration of appetite-related hormones in response to breakfasts of different energy contents, between active and inactive men. Sixteen healthy nonobese (body mass index = 18.5–27 kg/m2) adult males (nine active and seven inactive) participated in this study. Participants were given a high-energy (570 kcal) or a low-energy (205 kcal) breakfast in a random order. Subjective feelings of appetite and plasma concentrations of active ghrelin, active glucagon-like peptide-1, total peptide YY (PYY), cholecystokinin, and insulin were measured in fasting and every 30 min up to 2.5 hr, in response to both breakfasts. Mixed analysis of variance (fat mass [in percentage] as a covariate) revealed a higher concentration of active ghrelin and lower concentration of glucagon-like peptide-1, and cholecystokinin after the low-energy breakfast (p < .001 for all). Postprandial concentration of PYY was greater after the high energy compared with the low energy, but for inactive participants only (p = .014). Active participants had lower postprandial concentrations of insulin than inactive participants (p < .001). Differences in postprandial insulin between breakfasts were significantly lower in active compared with inactive participants (p < .001). Physical activity seems to modulate the postprandial plasma concentration of insulin and PYY after the intake of breakfasts of different energy contents, and that may contribute, at least partially, to the differences in short-term appetite control between active and inactive individuals.

scholarly journals Resveratrol Modulates the Gut-Brain Axis: Focus on Glucagon-Like Peptide-1, 5-HT, and Gut Microbiota

2020 ◽  
Vol 12 ◽  
Author(s):  
Ji Yeon Chung ◽  
Jae-Ho Jeong ◽  
Juhyun Song
Keyword(s):  
Stress Condition ◽  
Gastrointestinal Diseases ◽  
Regulatory Function ◽  
Specific Mechanism ◽  
Cns Inflammation ◽  
Natural Polyphenol ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Brain ◽  
Therapeutic Substance

Resveratrol is a natural polyphenol that has anti-aging and anti-inflammatory properties against stress condition. It is reported that resveratrol has beneficial functions in various metabolic and central nervous system (CNS) diseases, such as obesity, diabetes, depression, and dementia. Recently, many researchers have emphasized the connection between the brain and gut, called the gut–brain axis, for treating both CNS neuropathologies and gastrointestinal diseases. Based on previous findings, resveratrol is involved in glucagon-like peptide 1 (GLP-1) secreted by intestine L cells, the patterns of microbiome in the intestine, the 5-hydroxytryptamine (5-HT) level, and CNS inflammation. Here, we review recent evidences concerning the relevance and regulatory function of resveratrol in the gut–brain axis from various perspectives. Here, we highlight the necessity for further study on resveratrol's specific mechanism in the gut–brain axis. We present the potential of resveratrol as a natural therapeutic substance for treating both neuropathology and gastrointestinal dysfunction.

Identification of Glucagon-Like Peptide-1(7–36) Amide in Rat Brain

1989 ◽  
Vol 26 (2) ◽  
pp. 169-171 ◽  
Author(s):  
S Yoshimoto ◽  
M Hirota ◽  
C Ohboshi ◽  
K Shima
Keyword(s):  
Rat Brain ◽  
Anion Exchange ◽  
Gel Filtration ◽  
Anion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Experimental Conditions ◽  
Specific Radioimmunoassay ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Brain

Acid-urea extract of rat brain was examined by glucagon-like peptide-1 (GLP-1) specific radioimmunoassay. A single peak was observed which co-eluted with GLP-1(7–36)amide on gel filtration and anion exchange chromatography. In contrast, GLP-1(1–37) was not detected under our experimental conditions. The fact that GLP-1 (7–36)amide, but not GLP-1(1–37), was present in rat brain suggests that preproglucagon was processed in the brain in the same manner as in the intestine and not as in the pancreas.

Molecular mechanisms underlying nutrient-stimulated incretin secretion

2010 ◽  
Vol 12 ◽  
Author(s):  
Helen E. Parker ◽  
Frank Reimann ◽  
Fiona M. Gribble
Keyword(s):  
Drug Discovery ◽  
Molecular Mechanisms ◽  
Fat Metabolism ◽  
Potential Range ◽  
Incretin Hormones ◽  
Appetite Control ◽  
K Cells ◽  
Incretin Secretion ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from enteroendocrine cells in the intestinal epithelium in response to nutrient ingestion. The actions of GLP-1 and GIP – not only on local gut physiology but also on glucose homeostasis, appetite control and fat metabolism – have made these hormones an attractive area for drug discovery programmes. The potential range of strategies to target the secretion of these hormones therapeutically has been limited by an incomplete understanding of the mechanisms underlying their release. The use of organ and whole-animal perfusion techniques, cell line models and primary L- and K-cells has led to the identification of a variety of pathways involved in the sensing of carbohydrate, fat and protein in the gut lumen. This review focuses on our current understanding of these signalling mechanisms that might underlie nutrient responsiveness of L- and K-cells.

Appetite hormones and addiction

2018 ◽  
Author(s):  
David J. Nutt ◽  
Liam J. Nestor
Keyword(s):  
Eating Disorder ◽  
Food Intake ◽  
Food Consumption ◽  
Neural Substrates ◽  
Reward Sensitivity ◽  
Substance Addiction ◽  
Alcohol And Drugs ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Brain

Many of the same behavioural and brain disturbances observed in addiction are also seen in obesity and binge-eating disorder. This suggests that there are shared neural substrates between substance addiction and compulsive food consumption. Food intake and appetite are regulated by numerous appetite hormones that exert their effects through brain systems involved in reward sensitivity, stress, impulsivity, and compulsivity. There is now emerging evidence that appetite hormones (e.g. ghrelin, glucagon-like peptide-1, orexin) can modulate addictive behaviours (e.g. craving) and the intake of alcohol and drugs. Therefore, there is an emerging shift into a new field of testing drugs that affect appetite hormones and their receptors in the brain, and their use in regulating the brain mechanisms that lead to relapse in addiction disorders.

De Novo Arteriovenous Malformation Growth Secondary to Implantation of Genetically Modified Allogeneic Mesenchymal Stem Cells in the Brain

Neurosurgery ◽  
2015 ◽  
Vol 78 (4) ◽  
pp. E596-E600 ◽  
Author(s):  
Makoto Nakamura ◽  
Amir Samii ◽  
Josef M. Lang ◽  
Friedrich Götz ◽  
Madjid Samii ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Arteriovenous Malformation ◽  
De Novo ◽  
Genetically Modified ◽  
Biological Drug ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Brain

Abstract BACKGROUND AND IMPORTANCE: Local biological drug delivery in the brain is an innovative field of medicine that developed rapidly in recent years. Our report illustrates a unique case of de novo development of a cerebral arteriovenous malformation (AVM) after implantation of genetically modified allogeneic mesenchymal stem cells in the brain. CLINICAL PRESENTATION: A 50-year-old man was included in a prospective clinical study (study ID number CM GLP-1/01, 2007-004516-31) investigating a novel neuroprotective approach in stroke patients to prevent perihematomal neuronal damage. In this study, alginate microcapsules containing genetically modified allogeneic mesenchymal stem cells producing the neuroprotective glucagon-like peptide-1 (GLP-1) were implanted. Three years later, the patient presented with aphasia and a focal seizure due to a new left frontal intracerebral hemorrhage. Angiography revealed a de novo left frontal AVM. CONCLUSION: The development of an AVM within a period of 3 years after implantation of the glucagon-like peptide-1–secreting mesenchymal stem cells suggests a possible relationship. This case exemplifies that further investigations are necessary to assess the safety of genetically modified cell lines for local biological drug delivery in the brain.

Sign in / Sign up

Export Citation Format

Share Document