Mechanisms behind GLP-1 induced weight loss

2008 ◽  
Vol 8 (2_suppl) ◽  
pp. S34-S41 ◽  
Author(s):  
Philip J Larsen
Keyword(s):  
Energy Homeostasis ◽  
Caloric Intake ◽  
Underlying Mechanism ◽  
Negative Energy ◽  
Incretin Hormone ◽  
Dipeptidyl Peptidase 4 ◽  
Control Food ◽  
The Central Nervous System ◽  
Glucagon Like Peptide 1 ◽  
Control Food Intake

Endogenous glucagon-like peptide-1 (GLP-1) is an incretin hormone that plays an important role in maintaining pancreatic function as well as caloric intake. Since the advent of GLP-1 receptor agonists resistant to dipeptidyl peptidase-4 (DPP-4) (degradation, it has become clear that their chronic use promotes negative energy balance. With regard to their effects on body weight, the principal action of GLP-1 agonists is mediated via their inhibition of eating. In searching for the underlying mechanism of GLP-1 receptor agonist-induced anorexic effect, scientists have discovered pathways in the central nervous system, as well as in the periphery. This review describes emerging knowledge of a peripheral endocrine GLP-1 system mediating its activity through a central ascending GLP-1 pathway and targeting hypothalamic sites involved in the regulation of energy homeostasis. Thus peripheral and central GLP-1 sensitive pathways appear to be organised to co-operatively help control food intake and body weight.Br J Diabetes Vasc Dis 2008;8 (Suppl 2): S34—S41

scholarly journals Obesity and Appetite Control

2012 ◽  
Vol 2012 ◽  
pp. 1-19 ◽  
Author(s):  
Keisuke Suzuki ◽  
Channa N. Jayasena ◽  
Stephen R. Bloom
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Peptide Yy ◽  
Gut Hormones ◽  
Appetite Control ◽  
Control Food ◽  
Adiposity Signals ◽  
Term Energy ◽  
Glucagon Like Peptide 1 ◽  
Control Food Intake

Obesity is one of the major challenges to human health worldwide; however, there are currently no effective pharmacological interventions for obesity. Recent studies have improved our understanding of energy homeostasis by identifying sophisticated neurohumoral networks which convey signals between the brain and gut in order to control food intake. The hypothalamus is a key region which possesses reciprocal connections between the higher cortical centres such as reward-related limbic pathways, and the brainstem. Furthermore, the hypothalamus integrates a number of peripheral signals which modulate food intake and energy expenditure. Gut hormones, such as peptide YY, pancreatic polypeptide, glucagon-like peptide-1, oxyntomodulin, and ghrelin, are modulated by acute food ingestion. In contrast, adiposity signals such as leptin and insulin are implicated in both short- and long-term energy homeostasis. In this paper, we focus on the role of gut hormones and their related neuronal networks (the gut-brain axis) in appetite control, and their potentials as novel therapies for obesity.

Effect of a protein preload on food intake and satiety feelings in response to duodenal fat perfusions in healthy male subjects

2005 ◽  
Vol 289 (4) ◽  
pp. R1042-R1047 ◽  
Author(s):  
Sibylle Oesch ◽  
Lukas Degen ◽  
Christoph Beglinger
Keyword(s):  
Food Intake ◽  
Synergistic Effect ◽  
Peptide Yy ◽  
Caloric Intake ◽  
Healthy Male ◽  
Double Blind ◽  
Control Food ◽  
Initial Hypothesis ◽  
Glucagon Like Peptide 1 ◽  
Control Food Intake

The control of food intake and satiety requires a coordinated interplay. Oral protein and duodenal fat inhibit food intake and induce satiety, but their interactive potential is unclear. Our aim was therefore to investigate the interactions between an oral protein preload and intraduodenal (ID) fat on food intake and satiety feelings. Twenty healthy male volunteers were studied in a randomized, double-blind, four-period crossover design. On each study day, subjects underwent one of the following treatments: 1) water preload plus ID saline perfusion, 2) water preload plus ID fat perfusion, 3) protein preload plus ID saline perfusion, or 4) protein preload plus ID fat perfusion. Subjects were free to eat and drink as much as they wished. An oral protein preload significantly reduced caloric intake (19%, P < 0.01). Simultaneous administration of an oral protein preload and ID fat did not result in a positive synergistic effect with respect to caloric consumption, rejecting the initial hypothesis that the two nutrients exert a positive synergistic effect on food intake. An oral protein preload but not ID fat altered the feelings of hunger and fullness. These data indicate that the satiety effect of an oral protein preload is not amplified by ID fat; indeed, the effect of a protein preload does not seem to be mediated by cholecystokinin, glucagon-like peptide-1, or peptide YY. Much more information is necessary to understand the basic physiological mechanisms that control food intake and satiety.

scholarly journals The Function of Gastrointestinal Hormones in Obesity—Implications for the Regulation of Energy Intake

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1839
Author(s):  
Mona Farhadipour ◽  
Inge Depoortere
Keyword(s):  
Energy Homeostasis ◽  
Gastric Bypass Surgery ◽  
Gastrointestinal Hormones ◽  
Enteroendocrine Cells ◽  
Hormone Balance ◽  
Gut Hormone ◽  
Control Food ◽  
Induce Weight Loss ◽  
Novel Strategy ◽  
Control Food Intake

The global burden of obesity and the challenges of prevention prompted researchers to investigate the mechanisms that control food intake. Food ingestion triggers several physiological responses in the digestive system, including the release of gastrointestinal hormones from enteroendocrine cells that are involved in appetite signalling. Disturbed regulation of gut hormone release may affect energy homeostasis and contribute to obesity. In this review, we summarize the changes that occur in the gut hormone balance during the pre- and postprandial state in obesity and the alterations in the diurnal dynamics of their plasma levels. We further discuss how obesity may affect nutrient sensors on enteroendocrine cells that sense the luminal content and provoke alterations in their secretory profile. Gastric bypass surgery elicits one of the most favorable metabolic outcomes in obese patients. We summarize the effect of different strategies to induce weight loss on gut enteroendocrine function. Although the mechanisms underlying obesity are not fully understood, restoring the gut hormone balance in obesity by targeting nutrient sensors or by combination therapy with gut peptide mimetics represents a novel strategy to ameliorate obesity.

scholarly journals The Role of DPP4 Activity in Cardiovascular Districts: In Vivo and In Vitro Evidence

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
L. Pala ◽  
C. M. Rotella
Keyword(s):  
Minimal Risk ◽  
Incretin Hormone ◽  
Dipeptidyl Peptidase 4 ◽  
Beneficial Effects ◽  
Positive Effects ◽  
Glucagon Like Peptide 1 ◽  
A Site

The introduction of incretin hormone-based therapies represents a novel therapeutic strategy, since these drugs not only improve glycemia with minimal risk of hypoglycemia, but also have other extraglycemic beneficial effects. These agents, which are effective in improving glucose control, could also have positive effects on the incidence of cardiovascular events. The aim of this review is to summarize the present literature about the role of dipeptidyl peptidase 4 (DPP4) in cardiovascular districts, not only strictly correlated to its effect on glucagon-like peptide-1 (GLP-1) circulating levels, but also to what is known about possible cardiovascular actions. Actually, DPP4 is known to be present in many cells and tissues and its effects go beyond purely metabolic aspects. Almost always the inhibition of DPP4 activity is associated with improved cardiovascular profile, but it has shown to possess antithrombotic properties and these different effects could be connected with a site and/or species specificity of DPP4. Certainly, DPP4 seems to exert many functions, both directly and indirectly, on cardiovascular districts, opening new possibilities of prevention and treatment of complications at this level, not only in patients affected by diabetes mellitus.

scholarly journals Peptide YY, appetite and food intake

2005 ◽  
Vol 64 (2) ◽  
pp. 213-216 ◽  
Author(s):  
C. W. le Roux ◽  
S. R. Bloom
Keyword(s):  
Food Intake ◽  
Peptide Yy ◽  
Energy Content ◽  
Peak Plasma ◽  
Evolutionary Relationship ◽  
Gut Hormones ◽  
Amino Acid Peptide ◽  
Control Food ◽  
Glucagon Like Peptide 1 ◽  
Control Food Intake

Obesity is taking on pandemic proportions. The laws of thermodynamics, however, remain unchanged, as energy will be stored if less energy is expended than consumed; the storage is usually in the form of adipose tissue. Several neural, humeral and psychological factors control the complex process known as appetite. Recently, a close evolutionary relationship between the gut and brain has become apparent. The gut hormones regulate important gastrointestinal functions such as motility, secretion, absorption, provide feedback to the central nervous system on availability of nutrients and may play a part in regulating food intake. Peptide YY (PYY) is a thirty-six amino acid peptide related to neuropeptide Y (NPY) and is co-secreted with glucagon-like peptide 1. Produced by the intestinal L-cells, the highest tissue concentrations of PYY are found in distal segments of the gastrointestinal tract, although it is present throughout the gut. Following food intake PYY is released into the circulation. PYY concentrations are proportional to meal energy content and peak plasma levels appear postprandially after 1 h. PYY3-36 is a major form of PYY in both the gut mucosal endocrine cells and the circulation. Peripheral administration of PYY3-36 inhibits food intake for several hours in both rodents and man. The binding of PYY3-36 to the Y2 receptor leads to an inhibition of the NPY neurones and a possible reciprocal stimulation of the pro-opiomelanocortin neurones. Thus, PYY3-36 appears to control food intake by providing a powerful feedback on the hypothalamic circuits. The effect on food intake has been demonstrated at physiological concentrations and, therefore, PYY3-36 may be important in the everyday regulation of food intake.

Neurobiology of food choices-between energy homeostasis, reward system, and neuroeconomics

e-Neuroforum ◽  
2016 ◽  
Vol 22 (1) ◽  
Author(s):  
Laura Enax ◽  
Bernd Weber
Keyword(s):  
Energy Homeostasis ◽  
Health Care Systems ◽  
Reward System ◽  
Feeding Regulation ◽  
Control Food ◽  
Care Systems ◽  
Food Decisions ◽  
Short And Long Term ◽  
Control Food Intake ◽  
Internal And External Factors

AbstractThe rate of patients with obesity has been rapidly increasing, and this imposes a heavy economic burden on health-care systems. Food decisions, under the influence of different internal and external factors, lie at the core of this increasing health problem. Due to the biological necessity to consume sufficient amounts of food and to correctly regulate energy expenditure, there are different systems that control food intake. This article first focuses on neurobiological and hormonal foundations and explains various metabolic short- and long-term signals, such as leptin, insulin, and ghrelin. We then also present genetic factors, which directly or indirectly (via other genes or environmental influences) may affect nutritional status. Since the consumption of high-caloric foods is accompanied by dopamine release and the activation of the brain’s reward system, we will then present the interdependence of metabolic and reward systems. Last, we will present a neuroeconomic perspective that complements research on metabolic and hedonic feeding regulation.

scholarly journals Leptin and Beyond: Actors in Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1836
Author(s):  
Ines Barone ◽  
Cinzia Giordano
Keyword(s):  
Immune Response ◽  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Peptide Hormone ◽  
Tissue Mass ◽  
Adipose Tissue Mass ◽  
Control Food ◽  
Total Adipose Tissue ◽  
Control Food Intake ◽  
Reproductive Processes

Leptin is a 16-kDa multifunctional, neuroendocrine peptide hormone secreted by adipocytes in proportion to total adipose tissue mass, known to control food intake, energy homeostasis, immune response, and reproductive processes [...]

scholarly journals A sandwich ELISA for measurement of the primary glucagon-like peptide-1 metabolite

2017 ◽  
Vol 313 (3) ◽  
pp. E284-E291 ◽  
Author(s):  
Nicolai J. Wewer Albrechtsen ◽  
Ali Asmar ◽  
Frederik Jensen ◽  
Signe Törang ◽  
Lene Simonsen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Sandwich Elisa ◽  
Active Form ◽  
Primary Metabolite ◽  
Incretin Hormone ◽  
Dipeptidyl Peptidase 4 ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from the gastrointestinal tract. It is best known for its glucose-dependent insulinotropic effects. GLP-1 is secreted in its intact (active) form (7–36NH2) but is rapidly degraded by the dipeptidyl peptidase 4 (DPP-4) enzyme, converting >90% to the primary metabolite (9–36NH2) before reaching the targets via the circulation. Although originally thought to be inactive or antagonistic, GLP-1 9–36NH2 may have independent actions, and it is therefore relevant to be able to measure it. Because reliable assays were not available, we developed a sandwich ELISA recognizing both GLP-1 9–36NH2 and nonamidated GLP-1 9–37. The ELISA was validated using analytical assay validation guidelines and by comparing it to a subtraction-based method, hitherto employed for estimation of GLP-1 9–36NH2. Its accuracy was evaluated from measurements of plasma obtained during intravenous infusions (1.5 pmol × kg−1 × min−1) of GLP-1 7–36NH2 in healthy subjects and patients with type 2 diabetes. Plasma levels of the endogenous GLP-1 metabolite increased during a meal challenge in patients with type 2 diabetes, and treatment with a DPP-4 inhibitor fully blocked its formation. Accurate measurements of the GLP-1 metabolite may contribute to understanding its physiology and role of GLP-1 in diabetes.

scholarly journals Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenalin

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Lars Paeger ◽  
Ismene Karakasilioti ◽  
Janine Altmüller ◽  
Peter Frommolt ◽  
Jens Brüning ◽  
...  
Keyword(s):  
Adrenergic Receptors ◽  
Energy Homeostasis ◽  
Arcuate Nucleus ◽  
Differential Modulation ◽  
Control Food ◽  
Cell Type Specific ◽  
Control Food Intake ◽  
Perforated Patch Clamp ◽  
Β Adrenergic Receptors ◽  
Opposing Effect

In the arcuate nucleus of the hypothalamus (ARH) satiety signaling (anorexigenic) pro-opiomelanocortin (POMC)-expressing and hunger signaling (orexigenic) agouti-related peptide (AgRP)-expressing neurons are key components of the neuronal circuits that control food intake and energy homeostasis. Here, we assessed whether the catecholamine noradrenalin directly modulates the activity of these neurons in mice. Perforated patch clamp recordings showed that noradrenalin changes the activity of these functionally antagonistic neurons in opposite ways, increasing the activity of the orexigenic NPY/AgRP neurons and decreasing the activity of the anorexigenic POMC neurons. Cell type-specific transcriptomics and pharmacological experiments revealed that the opposing effect on these neurons is mediated by the activation of excitatory α1A - and β- adrenergic receptors in NPY/AgRP neurons, while POMC neurons are inhibited via α2A – adrenergic receptors. Thus, the coordinated differential modulation of the key hypothalamic neurons in control of energy homeostasis assigns noradrenalin an important role to promote feeding.

Sign in / Sign up

Export Citation Format

Share Document