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Science (New York, N.Y.) Aug 2023The mammalian gut secretes a family of multifunctional peptides that affect appetite, intestinal secretions, and motility whereas others regulate the microbiota. We have...
The mammalian gut secretes a family of multifunctional peptides that affect appetite, intestinal secretions, and motility whereas others regulate the microbiota. We have found that peptide YY (PYY), but not endocrine PYY, acts as an antimicrobial peptide (AMP) expressed by gut epithelial paneth cells (PC). PC-PYY is packaged into secretory granules and is secreted into and retained by surface mucus, which optimizes PC-PYY activity. Although PC-PYY shows some antibacterial activity, it displays selective antifungal activity against virulent hyphae-but not the yeast form. PC-PYY is a cationic molecule that interacts with the anionic surfaces of fungal hyphae to cause membrane disruption and transcriptional reprogramming that selects for the yeast phenotype. Hence, PC-PYY is an antifungal AMP that contributes to the maintenance of gut fungal commensalism.
Topics: Animals; Antifungal Agents; Antimicrobial Peptides; Candida; Paneth Cells; Peptide Fragments; Peptide YY; Symbiosis; Humans; Mice
PubMed: 37535745
DOI: 10.1126/science.abq3178 -
Nature Reviews. Endocrinology Mar 2017Anorexia nervosa is a psychiatric disorder characterized by altered body image, persistent food restriction and low body weight, and is associated with global endocrine... (Review)
Review
Anorexia nervosa is a psychiatric disorder characterized by altered body image, persistent food restriction and low body weight, and is associated with global endocrine dysregulation in both adolescent girls and women. Dysfunction of the hypothalamic-pituitary axis includes hypogonadotropic hypogonadism with relative oestrogen and androgen deficiency, growth hormone resistance, hypercortisolaemia, non-thyroidal illness syndrome, hyponatraemia and hypooxytocinaemia. Serum levels of leptin, an anorexigenic adipokine, are suppressed and levels of ghrelin, an orexigenic gut peptide, are elevated in women with anorexia nervosa; however, levels of peptide YY, an anorexigenic gut peptide, are paradoxically elevated. Although most, but not all, of these endocrine disturbances are adaptive to the low energy state of chronic starvation and reverse with treatment of the eating disorder, many contribute to impaired skeletal integrity, as well as neuropsychiatric comorbidities, in individuals with anorexia nervosa. Although 5-15% of patients with anorexia nervosa are men, only limited data exist regarding the endocrine impact of the disease in adolescent boys and men. Further research is needed to understand the endocrine determinants of bone loss and neuropsychiatric comorbidities in anorexia nervosa in both women and men, as well as to formulate optimal treatment strategies.
Topics: Adipokines; Anorexia Nervosa; Disease Management; Endocrine System Diseases; Female; Growth Hormone; Humans; Hypothalamo-Hypophyseal System; Leptin; Male; Pituitary-Adrenal System
PubMed: 27811940
DOI: 10.1038/nrendo.2016.175 -
Molecular and Cellular Endocrinology Nov 2019The pathophysiology of anorexia nervosa (AN) and bulimia nervosa (BN) are still poorly understood, but psychobiological models have proposed a key role for disturbances... (Review)
Review
The pathophysiology of anorexia nervosa (AN) and bulimia nervosa (BN) are still poorly understood, but psychobiological models have proposed a key role for disturbances in the neuroendocrines that signal hunger and satiety and maintain energy homeostasis. Mounting evidence suggests that many neuroendocrines involved in the regulation of homeostasis and body weight also play integral roles in food reward valuation and learning via their interactions with the mesolimbic dopamine system. Neuroimaging data have associated altered brain reward responses in this system with the dietary restriction and binge eating and purging characteristic of AN and BN. Thus, neuroendocrine dysfunction may contribute to or perpetuate eating disorder symptoms via effects on reward circuitry. This narrative review focuses on reward-related neuroendocrines that are altered in eating disorder populations, including peptide YY, insulin, stress and gonadal hormones, and orexins. We provide an overview of the animal and human literature implicating these neuroendocrines in dopaminergic reward processes and discuss their potential relevance to eating disorder symptomatology and treatment.
Topics: Animals; Anorexia Nervosa; Bulimia Nervosa; Ghrelin; Humans; Leptin; Neuroendocrinology; Reward
PubMed: 30395874
DOI: 10.1016/j.mce.2018.10.018 -
Journal of Obesity & Metabolic Syndrome Jun 2022Regulation of appetite is dependent on crosstalk between the gut and the brain, which is a pathway described as the gut-brain axis (GBA). Three primary... (Review)
Review
Regulation of appetite is dependent on crosstalk between the gut and the brain, which is a pathway described as the gut-brain axis (GBA). Three primary appetite-regulating hormones that are secreted in the gut as a response to eating a meal are glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), and peptide YY (PYY). When these hormones are secreted, the GBA responds to reduce appetite. However, secretion of these hormones and the response of the GBA can vary depending on the types of nutrients consumed. This narrative review describes how the gut secretes GLP-1, CCK, and PYY in response to proteins, carbohydrates, and fats. In addition, the GBA response based on the quality of the meal is described in the context of which meal types produce greater appetite suppression. Last, the beneficiary role of exercise as a mediator of appetite regulation is highlighted.
PubMed: 35718856
DOI: 10.7570/jomes22031 -
The Journal of Physiological Sciences :... Feb 2024Many hormones act on the hypothalamus to control hunger and satiety through various pathways closely associated with several factors. When food is present in the gastro... (Review)
Review
Many hormones act on the hypothalamus to control hunger and satiety through various pathways closely associated with several factors. When food is present in the gastro intestinal (GI) tract, enteroendocrine cells (EECs) emit satiety signals such as cholecystokinin (CCK), glucagon like peptide-1 (GLP-1) and peptide YY (PYY), which can then communicate with the vagus nerve to control food intake. More specifically, satiety has been shown to be particularly affected by the GLP-1 hormone and its receptor agonists that have lately been acknowledged as a promising way to reduce weight. In addition, there is increasing evidence that normal flora is also involved in the peripheral, central, and reward system that impact satiety. Moreover, neurologic pathways control satiety through neurotransmitters. In this review, we discuss the different roles of each of the GLP-1 hormone and its agonist, gut microbiomes, as well as neurotransmitters and their interconnected relation in the regulation of body's satiety homeostasis.
Topics: Cholecystokinin; Glucagon-Like Peptide 1; Peptide YY; Brain; Neurotransmitter Agents
PubMed: 38368346
DOI: 10.1186/s12576-024-00904-9 -
Physiological Reviews Jan 2017The efficacy of Roux-en-Y gastric-bypass (RYGB) and other bariatric surgeries in the management of obesity and type 2 diabetes mellitus and novel developments in... (Review)
Review
The efficacy of Roux-en-Y gastric-bypass (RYGB) and other bariatric surgeries in the management of obesity and type 2 diabetes mellitus and novel developments in gastrointestinal (GI) endocrinology have renewed interest in the roles of GI hormones in the control of eating, meal-related glycemia, and obesity. Here we review the nutrient-sensing mechanisms that control the secretion of four of these hormones, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine tyrosine [PYY(3-36)], and their contributions to the controls of GI motor function, food intake, and meal-related increases in glycemia in healthy-weight and obese persons, as well as in RYGB patients. Their physiological roles as classical endocrine and as locally acting signals are discussed. Gastric emptying, the detection of specific digestive products by small intestinal enteroendocrine cells, and synergistic interactions among different GI loci all contribute to the secretion of ghrelin, CCK, GLP-1, and PYY(3-36). While CCK has been fully established as an endogenous endocrine control of eating in healthy-weight persons, the roles of all four hormones in eating in obese persons and following RYGB are uncertain. Similarly, only GLP-1 clearly contributes to the endocrine control of meal-related glycemia. It is likely that local signaling is involved in these hormones' actions, but methods to determine the physiological status of local signaling effects are lacking. Further research and fresh approaches are required to better understand ghrelin, CCK, GLP-1, and PYY(3-36) physiology; their roles in obesity and bariatric surgery; and their therapeutic potentials.
Topics: Blood Glucose; Cholecystokinin; Eating; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Humans; Obesity; Peptide Fragments; Peptide YY
PubMed: 28003328
DOI: 10.1152/physrev.00031.2014 -
Gut Microbes 2022Durable spore-forming probiotics are increasingly formulated into foods, beverages, and dietary supplements. To help meet this demand, the safety and efficacy of daily... (Randomized Controlled Trial)
Randomized Controlled Trial
ABSTRACT
Durable spore-forming probiotics are increasingly formulated into foods, beverages, and dietary supplements. To help meet this demand, the safety and efficacy of daily supplementation of Bacillus subtilis BS50 for 6 weeks was investigated in a randomized, double-blind, placebo-controlled, parallel clinical trial of 76 healthy adults. Before and during supplementation, gastrointestinal symptoms were recorded daily using a multi-symptom questionnaire. Clinical chemistry, hematology, plasma lipids, and intestinal permeability and inflammation markers were measured at baseline and end of study. Compared to placebo, 2 × 10 colony-forming units (CFU) BS50 per day increased the proportion of participants showing improvement from baseline to week 6 in the composite score for bloating, burping, and flatulence (47.4% vs. 22.2%), whereby the odds of detecting an improvement were higher with BS50 (OR [95% CI]: 3.2 [1.1, 8.7], p = .024). Analyses of individual gastrointestinal symptoms indicate that BS50 increased the proportion of participants showing an improvement at week 6 compared to placebo for burping (44.7% vs. 22.2%, p = .041) and bloating (31.6% vs. 13.9%, p = .071), without affecting other symptoms. There were no clinically meaningful changes in clinical chemistry, hematology, plasma lipids and intestinal permeability and other inflammation markers. In conclusion, the results suggest that dietary supplementation of 2 × 10 CFU Bacillus subtilis BS50 per day is a well-tolerated and safe strategy to alleviate gas-related gastrointestinal symptoms in healthy adults.
ABBREVIATIONS
AE adverse event; BHD bowel habits diary; BMI body mass index; BSS Bristol Stool Scale; CFU colony-forming unit; CRP C-reactive protein; FGID functional gastrointestinal disorder; GI gastrointestinal; GITQ Gastrointestinal Tolerance Questionnaire; GLP-1 glucagon-like peptide 1; GSRS Gastrointestinal Symptom Rating Scale; HDL-C high-density lipoprotein-cholesterol; IBS irritable bowel syndrome; IL-10 interleukin-10; ITT intent-to-treat; LBP lipopolysaccharide binding protein; LDL-C low-density lipoprotein-cholesterol; PP per protocol; PYY peptide YY; TG triglyceride; total-C total cholesterol.
Topics: Adult; Humans; Bacillus subtilis; C-Reactive Protein; Cholesterol, LDL; Double-Blind Method; Gastrointestinal Diseases; Gastrointestinal Microbiome; Glucagon-Like Peptide 1; Interleukin-10; Irritable Bowel Syndrome; Lipopolysaccharides; Lipoproteins, HDL; Peptide YY; Probiotics; Treatment Outcome; Triglycerides
PubMed: 36269141
DOI: 10.1080/19490976.2022.2122668 -
The Journal of Clinical Endocrinology... Jan 2022
Topics: Bariatric Surgery; Gastric Bypass; Humans; Incretins
PubMed: 34543416
DOI: 10.1210/clinem/dgab694 -
Physiology & Behavior Sep 2021Food intake is tightly controlled by homeostatic signals sensitive to metabolic need for the regulation of body weight. This review focuses on the peripherally-secreted... (Review)
Review
Food intake is tightly controlled by homeostatic signals sensitive to metabolic need for the regulation of body weight. This review focuses on the peripherally-secreted gastrointestinal peptides (i.e., ghrelin, cholecystokinin, glucagon-like peptide 1, and peptide tyrosine tyrosine) that contribute to the control of appetite and discusses how these peptides or the signals arising from their release are disrupted in eating-related disorders across the weight spectrum, namely anorexia nervosa, bulimia nervosa, and obesity, and whether they are normalized following weight restoration or weight loss treatment. Further, the role of gut peptides in the pathogenesis and treatment response in human weight conditions as identified by rodent models are discussed. Lastly, we review the incretin- and hormone-based pharmacotherapies available for the treatment of obesity and eating-related disorders.
Topics: Appetite; Cholecystokinin; Eating; Ghrelin; Glucagon-Like Peptide 1; Peptide YY
PubMed: 33989649
DOI: 10.1016/j.physbeh.2021.113456