Glucagon-related peptides and the regulation of food intake in chickens.

The regulatory mechanisms underlying food intake in chickens have been a focus of research in recent decades to improve production efficiency when raising chickens. Lines of evidence have revealed that a number of brain-gut peptides function as a neurotransmitter or peripheral satiety hormone in the regulation of food intake both in mammals and chickens. Glucagon, a 29 amino acid peptide hormone, has long been known to play important roles in maintaining glucose homeostasis in mammals and birds. However, the glucagon gene encodes various peptides that are produced by tissue-specific proglucagon processing: glucagon is produced in the pancreas, whereas oxyntomodulin (OXM), glucagon-like peptide (GLP)-1 and GLP-2 are produced in the intestine and brain. Better understanding of the roles of these peptides in the regulation of energy homeostasis has led to various physiological roles being proposed in mammals. For example, GLP-1 functions as an anorexigenic neurotransmitter in the brain and as a postprandial satiety hormone in the peripheral circulation. There is evidence that OXM and GLP-2 also induce anorexia in mammals. Therefore, it is possible that the brain-gut peptides OXM, GLP-1 and GLP-2 play physiological roles in the regulation of food intake in chickens. More recently, a novel GLP and its specific receptor were identified in the chicken brain. This review summarizes current knowledge about the role of glucagon-related peptides in the regulation of food intake in chickens.

The forgotten members of the glucagon family.

From proglucagon, at least six final biologically active peptides are produced by tissue-specific post-translational processing. While glucagon and GLP-1 are the subject of permanent studies, the four others are usually left in the shadow, in spite of their large biological interest. The present review is devoted to oxyntomodulin and miniglucagon, not forgetting glicentin, although much less is known about it. Oxyntomodulin (OXM) and glicentin are regulators of gastric acid and hydromineral intestinal secretions. OXM is also deeply involved in the control of food intake and energy expenditure, properties that make this peptide a credible treatment of obesity if the question of administration is solved, as for any peptide. Miniglucagon, the C-terminal undecapeptide of glucagon which results from a secondary processing of original nature, displays properties antagonistic to that of the mother-hormone glucagon: (a) it inhibits glucose-, glucagon- and GLP-1-stimulated insulin release at sub-picomolar concentrations, (b) it reduces the in vivo insulin response to glucose with no change in glycemia, (c) it displays insulin-like properties at the cellular level using only a part of the pathway used by insulin, making it a good basis for developing a pharmacological workaround of insulin resistance.

Oxyntomodulin increases the concentrations of insulin and glucose in plasma but does not affect ghrelin secretion in Holstein cattle under normal physiological conditions.

Ghrelin, the natural ligand of the growth hormone secretagogue receptor (GHS-R1a), has been shown to stimulate growth hormone (GH) secretion. Regulation of ghrelin secretion in ruminants is not well studied. We investigated the effects of oxyntomodulin (OXM) and secretin on the secretions of ghrelin, insulin, glucagon, glucose, and nonesterified fatty acids (NEFA) in pre-ruminants (5 wk old) and ruminants (10 wk old) under normal physiological (feeding) conditions. Eight male Holstein calves (pre-ruminants: 52 +/- 1 kg body weight [BW]; and ruminants: 85 +/- 1 kg BW) were injected intravenously with 30 microg of OXM/kg BW, 50 microg of secretin/kg BW, and vehicle (0.1% bovine serum albumin [BSA] in saline as a control) in random order. Blood samples were collected, and plasma hormones and metabolites were analyzed using a double-antibody radioimmunoassay system and commercially available kits, respectively. We found that OXM increased the concentrations of insulin and glucose but did not affect the concentrations of ghrelin in both pre-ruminants and ruminants and that there was no effect of secretin on the concentrations of ghrelin, insulin, and glucose in these calves. We also investigated the dose-response effects of OXM on the secretion of insulin and glucose in 8 Holstein steers (401 +/- 1 d old, 398 +/- 10 kg BW). We found that OXM increased the concentrations of insulin and glucose even at physiological plasma concentrations, with a minimum effective dose of 0.4 microg/kg for the promotion of glucose secretion and 2 microg/kg for the stimulation of insulin secretion. These findings suggest that OXM takes part in glucose metabolism in ruminants.

Oxintomodulina e obesidade / Oxyntomodulin and obesity

Desde o descobrimento da leptina, avanços consideráveis foram obtidos na caracterização dos mecanismos hipotalâmicos do controle da ingestão alimentar e, atualmente, a oxintomodulina é reconhecida como um regulador da homeostase energética. O presente artigo de revisão enfoca algumas das mais relevantes inter-relações do hormônio oxintomodulina com o apetite, a homeostase energética e aspectos de seu papel na bioquímica e fisiologia nutricional. A oxintomodulina é um peptídeo intestinal anorexígeno produzido pelas células L do intestino. Recentes estudos têm demonstrado que em longo prazo a administração de oxintomodulina reduz a ingestão alimentar e o ganho de peso. Pesquisas em humanos têm verificado que o seu uso reduz o consumo energértico em 25 por cento. Portanto, a oxintomodulina representa uma potente terapia anti-obesidade. Entretanto, o mecanismo de ação da oxintomodulina ainda é desconhecido. Atuais evidências sugerem que tem ação via receptor do peptídeo semelhante ao glucagon 1. Além disso, a literatura mostra que, juntamente com a adoção de hábitos saudáveis e a mudança do estilo de vida, a oxintomodulina pode proporcionar menor avanço da obesidade.

Since the discovery of leptin, great advances occurred in the characterization of hypothalamic mechanisms involved in the control of food intake and oxyntomodulin is currently recognized as a homeostasis energy regulator. This review discusses the most important interrelationships between the hormone oxyntomodulin and appetite, energy homeostasis and aspects of its role in nutritional biochemistry and physiology. Oxyntomodulin is an anorexigenic peptide produced by the L cells of the small intestine. Recent studies have shown that long-term use of oxyntomodulin in rats leads to reduced food intake and weight gain. Studies in humans have demonstrated that its administration reduces food intake by 25 percent. Therefore, oxyntomodulin represents a potent anti-obesity therapy. However, its mechanism of action is unknown. Current evidence suggests that it acts via the peptide receptor similar to glucagon 1. Moreover, the literature shows that together with the adoption of healthy habits and lifestyle changes, oxyntomodulin can reduce weight gain.

[Gastrointestinal hormones in food intake control]. / Las hormonas gastrointestinales en el control de la ingesta de alimentos.

The discovery of gut hormones regulating the energy balance has aroused great interest in the scientific community. Some of these hormones modulate appetite and satiety, acting on the hypothalamus or the solitary tract nucleus in the brainstem. In general, the endocrine signals generated in the gut have direct or indirect (through the autonomous nervous system) anorexigenic effects. Only ghrelin, a gastric hormone, has been consistently associated with the initiation of food intake and is regarded as the main orexigenic signal both in animal models and humans. In this review, we provide a brief description of the major gastrointestinal hormones implicated in the regulation of food intake. Given the increased importance of food intake disturbances, especially obesity, a better understanding of the underlying mechanisms of action of the gastrointestinal hormones might contribute to the development of new molecules that could increase the therapeutic arsenal for treating obesity and its associated comorbidities.

Gut hormones: implications for the treatment of obesity.

Bariatric surgery is the only effective treatment for patients with morbid obesity. This is no solution to the present obesity pandemic however. Currently licensed non-surgical pharmaceuticals are of limited efficacy and alternatives are needed. Harnessing the body's own appetite-regulating signals is a desirable pharmacological strategy. The gastrointestinal tract has a prime role in sensing and signalling food intake to the brain. Gut hormones are key mediators of this information, including: peptide YY (PYY), pancreatic polypeptide (PP), glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXM), ghrelin, amylin and cholecystokinin (CCK). This review summarises the latest knowledge regarding the physiological and pathophysiological role of gut hormones in regulating our food intake and how this knowledge could guide, or has guided, the development of weight-loss drugs. Up-to-date outcomes of clinical trials are evaluated and directions for the future suggested.

Gut hormones and appetite control.

The gastrointestinal tract is the largest endocrine organ in the body. It secretes more than 20 different peptide hormones, which serve both a local regulatory function and provide a means by which the gut can regulate appetite and satiety. As the worldwide prevalence of obesity reaches epidemic proportions, the importance of delineating the mechanisms which regulate food intake becomes even more urgent. There is now a substantial body of work in both rodent and human models demonstrating the effects of these peptides on appetite and work is underway to therapeutically manipulate the gut-brain axis for the treatment of obesity. In addition, it may also be possible to use our understanding of the entero-endocrine system to treat calorie-deficient states.

Role of gut hormones in obesity.

A critical role for the gut in energy homeostasis has emerged. Gut hormones not only have a role in digestion but several of them have been found to modulate appetite in animals and humans. Current nonendocrine drugs for obesity are limited by their modest efficacies, and bariatric surgery is confined to use in severe cases. The discovery of important appetite-signaling pathways from the gut to the brain has led to the emergence of several gut hormone-derived drugs that are being investigated for clinical use. This article summarizes the physiology of the major gut hormones implicated in appetite regulation, and reviews clinical evidence that gives us insight into their potential as clinical treatments for obesity.

Mechanisms of disease: the role of gastrointestinal hormones in appetite and obesity.

The obesity epidemic is fast becoming one of the leading causes of mortality and morbidity worldwide. Over the past 30 years, gastrointestinal hormones have been increasingly understood to have an important role as regulators of appetite and energy balance in obese individuals. The levels of these hormones are modulated by bariatric surgery, and understanding how they are affected by such procedures can contribute to our comprehension of the underlying mechanisms by which these hormones affect obesity and its treatment. In this Review, we consider several gastrointestinal hormones that can contribute to obesity by modulating the activity of the gut-brain axis, and examine their specific effects on appetite, hunger and energy balance. Better understanding of the mechanisms by which these peptides exert their effects may enable the development of improved weight-loss medications and new treatments for obesity.

Gut and hormones and obesity.

Following the discovery of secretin in 1902, a host of further peptide hormones that are synthesised and released from the gastrointestinal tract have been identified. While their roles in the regulation of gastrointestinal function have been known for some time, it is now evident that many of these hormones also physiologically regulate energy balance. Our understanding of how gut hormones signal to the brain has advanced significantly in recent years. Several hormones, including peptide YY, pancreatic polypeptide, oxyntomodulin, glucagon-like peptide 1 and cholecystokinin function as satiety signals. In contrast, only ghrelin, produced by the stomach, has emerged as a putative hunger signal, appearing to act both as a meal initiator and a long-term body weight regulator. Recent research suggests that gut hormones can be manipulated to regulate energy balance in man and that obese subjects retain sensitivity to the actions of gut hormones. The worldwide obesity pandemic continues unabated, despite public health initiatives and current best therapy. Future gut hormone-based therapies may provide an effective and well-tolerated treatment for obesity.

The multiple faces of glucagon-like peptide-1--obesity, appetite, and stress: what is next? A review.

By itself, glucagon-like peptide-1(GLP-1) appears to be an excellent drug for appetite control and the treatment of obesity. Unfortunately, few enzymes, such as IV dipeptidyl peptidase and renal excretin, degrade and render GLP-1 inactive within minutes. A receptor agonist, exendin-4, with a longer biological half-life than GLP-1, has been tried. Subcutaneous injection of exendin-4 or continuous IV injection of GLP-1 warrants further research and investigation.

The role of oxyntomodulin and peptide tyrosine-tyrosine (PYY) in appetite control.

Oxyntomodulin and peptide tyrosine-tyrosine (PYY) are released from intestinal enteroendocrine cells in response to a meal. These circulating hormones are considered to be satiety signals, as they have been found to decrease food intake, body weight and adiposity in rodents. Their effect on energy homeostasis is mediated by the hypothalamus and brainstem, and several studies have demonstrated alterations in neuropeptide signaling within the arcuate nucleus. The weight loss that has been observed in animal models after repeated administration of oxyntomodulin and PYY has led to interest in developing these peptides as antiobesity therapies in humans. Indeed, preliminary studies have found that oxyntomodulin or PYY administration reduces food intake and body weight effectively in overweight human volunteers. This research suggests that modulation of these gut hormones could prove to be effective long-term therapies in the quest to combat the obesity epidemic.