Minireview: Gut Peptides Regulating Satiety

Abstract

The gastrointestinal tract and the pancreas release hormones regulating satiety and body weight. Ghrelin stimulates appetite, and glucagon-like peptide-1, oxyntomodulin, peptide YY, cholecystokinin, and pancreatic polypeptide inhibit appetite. These gut hormones act to markedly alter food intake in humans and rodents. Obesity is the current major cause of premature death in the United Kingdom, killing almost 1000 people per week. Worldwide, its prevalence is accelerating. There is currently no effective answer to the pandemic of obesity, but replacement of the low levels of peptide YY observed in the obese may represent an effective antiobesity therapy.

Pancreatic polypeptide in obese children before and after weight loss

“…It is difficult to distinguish between the effect of surgery and the reduction of body weight on gastrointestinal hormones in these studies, because the decreased postprandial PP release after surgery on the GI tract may be in part owing to the absence of gastric PP in obese children T Reinehr et al and duodenal food stimuli, vagal injury and lower blood glucose, which mainly regulate PP secretion. 5,25 As PP concentrations are decreased in obesity and increase in weight loss, PP levels seem to reflect long-term energy stores. It is not clear, how obesity can lead to decreased fasting PP levels in humans.…”

“…23,24 But it is difficult to distinguish between the effect of surgery on the gastrointestinal (GI) tract and the reduction of body weight on gastrointestinal hormone levels in these studies, because the decreased postprandial PP release after surgery on the GI tract may be in part due to the absence of gastric and duodenal food stimuli, vagal injury and lower blood glucose, which mainly regulate PP secretion. 5,25 Even less is known about the role of PP in pediatric obesity.…”

Effect of pramlintide on satiety and food intake in obese subjects and subjects with type 2 diabetes

“…This regulation may include the quantity of food consumed, as well as the absorption and disposition of ingested nutrients [1][2][3][4][5]. Specifically, there is growing recognition that peptide hormones secreted from the gut and from pancreatic islets in response to meals may act as humoral and/or neuronal feedback signals to the central nervous system (CNS), mediating the perception of fullness and satiation during meals (thus contributing to meal termination), and/or the maintenance of satiety after meals (thus affecting inter-meal intervals) [1][2][3][4][5].…”

“…This regulation may include the quantity of food consumed, as well as the absorption and disposition of ingested nutrients [1][2][3][4][5]. Specifically, there is growing recognition that peptide hormones secreted from the gut and from pancreatic islets in response to meals may act as humoral and/or neuronal feedback signals to the central nervous system (CNS), mediating the perception of fullness and satiation during meals (thus contributing to meal termination), and/or the maintenance of satiety after meals (thus affecting inter-meal intervals) [1][2][3][4][5]. Whether a given peptide hormone has a physiological role in the regulation of food intake and body weight is typically established by supporting evidence from animal studies (using gain-offunction studies with the peptide itself and loss-of-function studies with selective antagonists and/or gene knock-outs) and from clinical studies assessing the effect of the peptide on satiety and food intake in humans [1][2][3][4][5].…”

“…Specifically, there is growing recognition that peptide hormones secreted from the gut and from pancreatic islets in response to meals may act as humoral and/or neuronal feedback signals to the central nervous system (CNS), mediating the perception of fullness and satiation during meals (thus contributing to meal termination), and/or the maintenance of satiety after meals (thus affecting inter-meal intervals) [1][2][3][4][5]. Whether a given peptide hormone has a physiological role in the regulation of food intake and body weight is typically established by supporting evidence from animal studies (using gain-offunction studies with the peptide itself and loss-of-function studies with selective antagonists and/or gene knock-outs) and from clinical studies assessing the effect of the peptide on satiety and food intake in humans [1][2][3][4][5]. To date, randomised, controlled crossover studies in humans have reported an increase in food intake at a buffet meal following the administration of the gastric hormone ghrelin [6], and a decrease following the administration of the gut hormones cholecystokinin (CCK) [7,8], glucagon-like peptide-1 (GLP-1) [9][10][11], oxyntomodulin [12] and peptide YY3-36 [13,14], and the islet hormones glucagon [15], pancreatic polypeptide [16] and somatostatin [17].…”