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Appetite, the enteroendocrine system, gastrointestinal disease and obesity.
Crooks, B, Stamataki, NS, McLaughlin, JT
The Proceedings of the Nutrition Society. 2021;(1):50-58
Abstract
The enteroendocrine system is located in the gastrointestinal (GI) tract, and makes up the largest endocrine system in the human body. Despite that, its roles and functions remain incompletely understood. Gut regulatory peptides are the main products of enteroendocrine cells, and play an integral role in the digestion and absorption of nutrients through their effect on intestinal secretions and gut motility. Several peptides, such as cholecystokinin, polypeptide YY and glucagon-like peptide-1, have traditionally been reported to suppress appetite following food intake, so-called satiety hormones. In this review, we propose that, in the healthy individual, this system to regulate appetite does not play a dominant role in normal food intake regulation, and that there is insufficient evidence to wholly link postprandial endogenous gut peptides with appetite-related behaviours. Instead, or additionally, top-down, hedonic drive and neurocognitive factors may have more of an impact on food intake. In GI disease however, supraphysiological levels of these hormones may have more of an impact on appetite regulation as well as contributing to other unpleasant abdominal symptoms, potentially as part of an innate response to injury. Further work is required to better understand the mechanisms involved in appetite control and unlock the therapeutic potential offered by the enteroendocrine system in GI disease and obesity.
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Emerging role of GIP and related gut hormones in fertility and PCOS.
Moffett, RC, Naughton, V
Peptides. 2020;:170233
Abstract
Gastric inhibitory polypeptide (GIP) is best known as an incretin hormone released by enteroendocrine K-cells in response to feeding and stimulates insulin release to regulate blood glucose and nutrient homeostasis. More recently GIP has been ascribed a positive role in lipid metabolism, bone strength, cardiovascular function and cognition. The present paper considers an emerging role of GIP and related gut hormones in fertility and especially polycystic ovarian syndrome (PCOS). Key evidence concerns restoration of fertility in women with gross obesity and PCOS following bariatric surgery. This is considered to reflect indirect effects mediated by alleviation of insulin resistance together with possible direct effects of surgically induced changes of GIP, GLP-1 and related peptide hormones on ovaries and the hypothalamic-pituitary-adrenal axis. Further studies are required to determine inter-relationships between the hormones and cellular mechanisms involved but these observations suggest that GIP and other gut may provide a novel therapeutic approach for PCOS and other reproductive disorders.
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The new place of enterohormones in intestinal failure.
Daoud, DC, Joly, F
Current opinion in clinical nutrition and metabolic care. 2020;(5):344-349
Abstract
PURPOSE OF REVIEW Since the approval of teduglutide, a glucagon-like peptide-2 (GLP-2) analog, for the treatment of patients with short bowel syndrome (SBS) associated with intestinal failure, enterohormone therapy has received significant interest and is becoming the first choice of treatment in selected patients. As such, it is paramount to assess and understand the new place of hormonal therapy in the algorithm of treatments in SBS-intestinal failure. RECENT FINDINGS Specialized intestinal failure units have recently reported their outcomes with teduglutide to evaluate if they are consistent with the phase III trials results. SBS-intestinal failure patients are very heterogenous including their response to this treatment, hence the importance of real-life studies beyond the context of clinical trials. Moreover, it is essential to find a consensus on criteria identifying candidate patients for teduglutide. In addition, the impact of teduglutide on quality of life and its cost-effectiveness are emerging as well as new enterohormone treatments are being studied whether it is long action GLP-2 analog or other ileocolonic break hormones like glucagon-like peptide-1 analog. SUMMARY Hormonotherapy is currently modifying the natural history of patients with SBS-intestinal failure by decreasing their need for parenteral support and possibly even complications associated with long-term parenteral support. Enterohormone treatment is now the cornerstone in SBS-intestinal failure and should be offered as a first-line therapy to selected patients.
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4.
Appetite control: hormones or diet strategies?
Freire, RH, Alvarez-Leite, JI
Current opinion in clinical nutrition and metabolic care. 2020;(5):328-335
Abstract
PURPOSE OF REVIEW Appetite control results from metabolic, behavioral, and environmental factors that influence hunger and the desire to eat. We summarize the latest advances in the hormonal and nutritional strategies to control appetite and reduce hunger. RECENT FINDINGS The fed-hunger-state is regulated by central and peripheric hormones, which modulate energy balance. Leptin, insulin, ghrelin, peptide YY (PYY), and other gut-derived peptides represent the main appetite controllers. The role of orexins, obestatin, and liver-expressed antimicrobial peptide 2 has been uncovered recently. New insights have demonstrated the role of hippocampal activity as a possible mechanism of action. Glucagon-like peptide 1 (GLP1) receptor agonists are well known agents controlling appetite. Association of GLP1 receptor agonist, PYY, or glucose-dependent insulinotropic polypeptide agonists have been tested as new approaches. Appetite-control hormones have also risen as factors involved in the efficacy of bariatric procedures. High-protein, ketogenic diet, and intermittent fasting have been described as nutritional strategies to reduce appetite, although the physiological mechanism and long-term safety remains unclear. SUMMARY Appetite control has been an important target for the treatment of obesity and associated disorders. New studies have demonstrated promising adoption of dietary approaches, hormone-based drugs, and bariatric surgery to control energy intake. Further research will establish a significant association, benefits, and safety of these new therapies.
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The Implication of Gut Hormones in the Regulation of Energy Homeostasis and Their Role in the Pathophysiology of Obesity.
Koliaki, C, Liatis, S, Dalamaga, M, Kokkinos, A
Current obesity reports. 2020;(3):255-271
Abstract
PURPOSE OF REVIEW This review provides an update on the role of gut hormones and their interactions in the regulation of energy homeostasis, describes gut hormone adaptations in obesity and in response to weight loss, and summarizes the current evidence on the role of gut hormone-based therapies for obesity treatment. RECENT FINDINGS Gut hormones play a key role in regulating eating behaviour, energy and glucose homeostasis. Dysregulated gut hormone responses have been proposed to be pathogenetically involved in the development and perpetuation of obesity. Summarizing the major gut hormone changes in obesity, obese individuals are characterized by blunted postprandial ghrelin suppression, loss of premeal ghrelin peaks, impaired diurnal ghrelin variability and reduced fasting and postprandial levels of anorexigenic peptides. Adaptive alterations of gut hormone levels are implicated in weight regain, thus complicating hypocaloric dietary interventions, and can further explain the profound weight loss and metabolic improvement following bariatric surgery. A plethora of compounds mimicking gut hormone changes after bariatric surgery are currently under investigation, introducing a new era in the pharmacotherapy of obesity. The current trend is to combine different gut hormone receptor agonists and target multiple systems simultaneously, in order to replicate as closely as possible the gut hormone milieu after bariatric surgery and circumvent the counter-regulatory adaptive changes associated with dietary energy restriction. An increasing number of preclinical and early-phase clinical trials reveal the additive benefits obtained with dual or triple gut peptide receptor agonists in reducing body weight and improving glycaemia. Gut hormones act as potent regulators of energy and glucose homeostasis. Therapeutic strategies targeting their levels or receptors emerge as a promising approach to treat patients with obesity and hyperglycaemia.
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6.
Mechanisms controlling hormone secretion in human gut and its relevance to metabolism.
Martin, AM, Sun, EW, Keating, DJ
The Journal of endocrinology. 2019;(1):R1-R15
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Abstract
The homoeostatic regulation of metabolism is highly complex and involves multiple inputs from both the nervous and endocrine systems. The gut is the largest endocrine organ in our body and synthesises and secretes over 20 different hormones from enteroendocrine cells that are dispersed throughout the gut epithelium. These hormones include GLP-1, PYY, GIP, serotonin, and CCK, each of whom play pivotal roles in maintaining energy balance and glucose homeostasis. Some are now the basis of several clinically used glucose-lowering and weight loss therapies. The environment in which these enteroendocrine cells exist is also complex, as they are exposed to numerous physiological inputs including ingested nutrients, circulating factors and metabolites produced from neighbouring gut microbiome. In this review, we examine the diverse means by which gut-derived hormones carry out their metabolic functions through their interactions with different metabolically important organs including the liver, pancreas, adipose tissue and brain. Furthermore, we discuss how nutrients and microbial metabolites affect gut hormone secretion and the mechanisms underlying these interactions.
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Effect of physical exercise and training on gastrointestinal hormones in populations with different weight statuses.
Zouhal, H, Sellami, M, Saeidi, A, Slimani, M, Abbassi-Daloii, A, Khodamoradi, A, El Hage, R, Hackney, AC, Ben Abderrahman, A
Nutrition reviews. 2019;(7):455-477
Abstract
Several types of hormones exert control over appetite in humans. This narrative review explores the effects of exercise and training on the concentrations of gastrointestinal hormones in healthy and obese individuals. It focuses on the major hormones of appetite regulation: ghrelin, glucagon-like peptide 1, peptide YY, cholecystokinin, leptin, and oxyntomodulin. In normal-weight and overweight individuals, responses to most of these hormones depend on the intensity of exercise and training. However, findings in obese individuals are limited in number and, to some degree, contradictory. Although some gastrointestinal hormones have been studied extensively (eg, leptin), most have not been investigated systematically. Further research is required to confirm the effectiveness of exercise and training on gut hormones and to better understand the effect of gut hormones on appetite and hunger suppression in individuals with obesity. Investigations to elucidate the impact of various forms of exercise that have recently engaged the public interest, eg, high-intensity interval training or concurrent aerobic and resistance training, are warranted.
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Will medications that mimic gut hormones or target their receptors eventually replace bariatric surgery?
Kokkinos, A, Tsilingiris, D, le Roux, CW, Rubino, F, Mantzoros, CS
Metabolism: clinical and experimental. 2019;:153960
Abstract
Bariatric surgery is currently the most effective therapeutic modality through which sustained beneficial effects on weight loss and metabolic improvement are achieved. During recent years, indications for bariatric surgery have been expanded to include cases of poorly controlled type 2 (T2DM) diabetes mellitus in lesser extremes of body weight. A spectrum of the beneficial effects of surgery is attributed to robust changes of postprandial gut peptide responses that are observed post operatively. Consolidated knowledge regarding gut peptide physiology as well as emerging new evidence shedding light on the mode of action of previously overlooked gut hormones provide appealing potential obesity and T2DM therapeutic perspectives. The accumulation of evidence from the effect of exogenous administration of native gut peptides alone or in combinations to humans as well as the development of mimetic agents exerting agonistic effects on combinations of gut hormone receptors pave the way for future integrated gut peptide-based treatments, which may mimic the effects of bariatric surgery.
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Diet in Irritable Bowel Syndrome (IBS): Interaction with Gut Microbiota and Gut Hormones.
El-Salhy, M, Hatlebakk, JG, Hausken, T
Nutrients. 2019;(8)
Abstract
Diet plays an important role not only in the pathophysiology of irritable bowel syndrome (IBS), but also as a tool that improves symptoms and quality of life. The effects of diet seem to be a result of an interaction with the gut bacteria and the gut endocrine cells. The density of gut endocrine cells is low in IBS patients, and it is believed that this abnormality is the direct cause of the symptoms seen in IBS patients. The low density of gut endocrine cells is probably caused by a low number of stem cells and low differentiation progeny toward endocrine cells. A low fermentable oligo-, di-, monosaccharide, and polyol (FODMAP) diet and fecal microbiota transplantation (FMT) restore the gut endocrine cells to the level of healthy subjects. It has been suggested that our diet acts as a prebiotic that favors the growth of a certain types of bacteria. Diet also acts as a substrate for gut bacteria fermentation, which results in several by-products. These by-products might act on the stem cells in such a way that the gut stem cells decrease, and consequently, endocrine cell numbers decrease. Changing to a low-FODMAP diet or changing the gut bacteria through FMT improves IBS symptoms and restores the density of endocrine cells.
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Gastrointestinal hormones in regulation of memory.
Mandal, A, Prabhavalkar, KS, Bhatt, LK
Peptides. 2018;:16-25
Abstract
The connection between the gastrointestinal hormones and the brain has been established many years ago. This relation is termed the gut-brain axis (GBA). The GBA is a bidirectional communication which not only regulates gastrointestinal homeostasis but is also linked with higher emotional and cognitive functions. Hypothalamus plays a critical role in the regulation of energy metabolism, nutrient partitioning and control of feeding behaviors. Various gut hormones are released inside the gastrointestinal tract on food intake. These hormones act peripherally and influence the different responses of the tissues to the food intake, but do also have effects on the brain. The hypothalamus, in turn, integrates visceral function with limbic system structures such as hippocampus, amygdala, and cerebral cortex. The hippocampus has been known for its involvement in the cognitive function and the modulation of synaptic plasticity. This review aims to establish the role of various gut hormones in learning and memory, through the interaction of various receptors in the hippocampus. Understanding their role in memory can also aid in finding novel therapeutic strategies for the treatment of the neurological disorders associated with memory dysfunctions.