-
Clinics and Research in Hepatology and... Feb 2022Food intake and energy expenditure are key regulators of body weight. To regulate food intake, the brain must integrate physiological signals and hedonic cues. The brain... (Review)
Review
Food intake and energy expenditure are key regulators of body weight. To regulate food intake, the brain must integrate physiological signals and hedonic cues. The brain plays an essential role in modulating the appropriate responses to the continuous update of the body energy-status by the peripheral signals and the neuronal pathways that generate the gut-brain axis. This regulation encompasses various steps involved in food consumption, include satiation, satiety, and hunger. It is important to have a comprehensive understanding of the mechanisms that regulate food consumption as well as to standardize the vocabulary for the steps involved. This review discusses the current knowledge of the regulation and the contribution peripheral and central signals at each step of the cycle to control appetite. We also highlight how food intake has been measured. The increasingly complex understanding of regulation and action mechanisms intervening in the gut-brain axis offers ambitious targets for new strategies to control appetite.
Topics: Appetite; Eating; Homeostasis; Humans; Hunger; Satiation
PubMed: 34481092
DOI: 10.1016/j.clinre.2021.101794 -
United European Gastroenterology Journal Jul 2021Different peripheral pathways are implicated in the regulation of the food ingestion-digestion cycle. (Review)
Review
BACKGROUND
Different peripheral pathways are implicated in the regulation of the food ingestion-digestion cycle.
METHODS
Narrative review on gastrointestinal mechanisms involved in satiety and hunger signalling.
RESULTS
Combined mechano- and chemoreceptors, peripherally released peptide hormones and neural pathways provide feedback to the brain to determine sensations of hunger (increase energy intake) or satiation (cessation of energy intake) and regulate the human metabolism. The gastric accommodation reflex, which consists of a transient relaxation of the proximal stomach during food intake, has been identified as a major determinant of meal volume, through activation of tension-sensitive gastric mechanoreceptors. Motilin, whose release is the trigger of gastric Phase 3, has been identified as the major determinant of return of hunger after a meal. In addition, the release of several peptide hormones such as glucagon-like peptide 1 (GLP-1), cholecystokinin as well as motilin and ghrelin contributes to gut-brain signalling with relevance to control of hunger and satiety. A number of nutrients, such as bitter tastants, as well as pharmacological agents, such as endocannabinoid receptor antagonists and GLP-1 analogues act on these pathways to influence hunger, satiation and food intake.
CONCLUSION
Gastrointestinal mechanisms such as gastric accommodation and motilin release are key determinants of satiety and hunger.
Topics: Animals; Cholecystokinin; Gastrointestinal Tract; Ghrelin; Glucagon-Like Peptide 1; Humans; Hunger; Motilin; Myoelectric Complex, Migrating; Satiation; Taste
PubMed: 34153172
DOI: 10.1002/ueg2.12097 -
Nature Reviews. Disease Primers Jul 2020The main inherited cardiac arrhythmias are long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia and Brugada syndrome. These rare... (Review)
Review
The main inherited cardiac arrhythmias are long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia and Brugada syndrome. These rare diseases are often the underlying cause of sudden cardiac death in young individuals and result from mutations in several genes encoding ion channels or proteins involved in their regulation. The genetic defects lead to alterations in the ionic currents that determine the morphology and duration of the cardiac action potential, and individuals with these disorders often present with syncope or a life-threatening arrhythmic episode. The diagnosis is based on clinical presentation and history, the characteristics of the electrocardiographic recording at rest and during exercise and genetic analyses. Management relies on pharmacological therapy, mostly β-adrenergic receptor blockers (specifically, propranolol and nadolol) and sodium and transient outward current blockers (such as quinidine), or surgical interventions, including left cardiac sympathetic denervation and implantation of a cardioverter-defibrillator. All these arrhythmias are potentially life-threatening and have substantial negative effects on the quality of life of patients. Future research should focus on the identification of genes associated with the diseases and other risk factors, improved risk stratification and, in particular for Brugada syndrome, effective therapies.
Topics: Anemia; Autoimmune Diseases; Disease Management; Dyspepsia; Gastritis, Atrophic; Humans; Satiety Response
PubMed: 32678103
DOI: 10.1038/s41572-020-0188-7 -
Molecules (Basel, Switzerland) Nov 2021Dietary fiber is a widely recognized nutrient for human health. Previous studies proved that dietary fiber has significant implications for gastrointestinal health by... (Review)
Review
Dietary fiber is a widely recognized nutrient for human health. Previous studies proved that dietary fiber has significant implications for gastrointestinal health by regulating the gut microbiota. Moreover, mechanistic research showed that the physiological functions of different dietary fibers depend to a great extent on their physicochemical characteristics, one of which is solubility. Compared with insoluble dietary fiber, soluble dietary fiber can be easily accessed and metabolized by fiber-degrading microorganisms in the intestine and produce a series of beneficial and functional metabolites. In this review, we outlined the structures, characteristics, and physiological functions of soluble dietary fibers as important nutrients. We particularly focused on the effects of soluble dietary fiber on human health via regulating the gut microbiota and reviewed their effects on dietary and clinical interventions.
Topics: Dietary Fiber; Energy Intake; Gastrointestinal Microbiome; Histone Deacetylase Inhibitors; Humans; Intestinal Absorption; Ligands; Molecular Structure; Polysaccharides; Receptors, G-Protein-Coupled; Satiation; Solubility
PubMed: 34833893
DOI: 10.3390/molecules26226802 -
Nature Metabolism Feb 2021The anorexigenic peptide glucagon-like peptide-1 (GLP-1) is secreted from gut enteroendocrine cells and brain preproglucagon (PPG) neurons, which, respectively, define...
The anorexigenic peptide glucagon-like peptide-1 (GLP-1) is secreted from gut enteroendocrine cells and brain preproglucagon (PPG) neurons, which, respectively, define the peripheral and central GLP-1 systems. PPG neurons in the nucleus tractus solitarii (NTS) are widely assumed to link the peripheral and central GLP-1 systems in a unified gut-brain satiation circuit. However, direct evidence for this hypothesis is lacking, and the necessary circuitry remains to be demonstrated. Here we show that PPG neurons encode satiation in mice, consistent with vagal signalling of gastrointestinal distension. However, PPG neurons predominantly receive vagal input from oxytocin-receptor-expressing vagal neurons, rather than those expressing GLP-1 receptors. PPG neurons are not necessary for eating suppression by GLP-1 receptor agonists, and concurrent PPG neuron activation suppresses eating more potently than semaglutide alone. We conclude that central and peripheral GLP-1 systems suppress eating via independent gut-brain circuits, providing a rationale for pharmacological activation of PPG neurons in combination with GLP-1 receptor agonists as an obesity treatment strategy.
Topics: Animals; Central Nervous System; Eating; Female; Gastrointestinal Tract; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Male; Mice; Mice, Inbred C57BL; Neurons; Peripheral Nervous System; Proglucagon; Receptors, Oxytocin; Satiety Response; Vagus Nerve
PubMed: 33589843
DOI: 10.1038/s42255-021-00344-4 -
Cell Jan 2020The function of central appetite neurons is instructing animals to ingest specific nutrient factors that the body needs. Emerging evidence suggests that individual... (Review)
Review
The function of central appetite neurons is instructing animals to ingest specific nutrient factors that the body needs. Emerging evidence suggests that individual appetite circuits for major nutrients-water, sodium, and food-operate on unique driving and quenching mechanisms. This review focuses on two aspects of appetite regulation. First, we describe the temporal relationship between appetite neuron activity and consumption behaviors. Second, we summarize ingestion-related satiation signals that differentially quench individual appetite circuits. We further discuss how distinct appetite and satiation systems for each factor may contribute to nutrient homeostasis from the functional and evolutional perspectives.
Topics: Animals; Appetite; Appetite Regulation; Brain; Feeding Behavior; Homeostasis; Humans; Hunger; Nervous System Physiological Phenomena; Neurons; Satiation; Sodium; Thirst
PubMed: 31923398
DOI: 10.1016/j.cell.2019.11.040 -
Nutrients Apr 2020Food ingestion induces a metered response of the digestive system. Initially, the upper digestive system reacts to process and extract meal substrates. Later, meal... (Review)
Review
Food ingestion induces a metered response of the digestive system. Initially, the upper digestive system reacts to process and extract meal substrates. Later, meal residues not absorbed in the small bowel, pass into the colon and activate the metabolism of resident microbiota. Food consumption also induces sensations that arise before ingestion (e.g., anticipatory reward), during ingestion (e.g., gustation), and most importantly, after the meal (i.e., the postprandial experience). The postprandial experience involves homeostatic sensations (satiety, fullness) with a hedonic dimension (digestive well-being, mood). The factors that determine the postprandial experience are poorly understood, despite their potential role in personalized diets and healthy eating habits. Current data suggest that the characteristics of the meal (amount, palatability, composition), the activity of the digestive system (suited processing), and the receptivity of the eater (influenced by multiple conditioning factors) may be important in this context.
Topics: Affect; Digestion; Eating; Feeding Behavior; Gastrointestinal Microbiome; Humans; Postprandial Period; Satiation; Satiety Response
PubMed: 32252402
DOI: 10.3390/nu12040986 -
A corticoamygdalar pathway controls reward devaluation and depression using dynamic inhibition code.Neuron Dec 2023Reward devaluation adaptively controls reward intake. It remains unclear how cortical circuits causally encode reward devaluation in healthy and depressed states. Here,...
Reward devaluation adaptively controls reward intake. It remains unclear how cortical circuits causally encode reward devaluation in healthy and depressed states. Here, we show that the neural pathway from the anterior cingulate cortex (ACC) to the basolateral amygdala (BLA) employs a dynamic inhibition code to control reward devaluation and depression. Fiber photometry and imaging of ACC pyramidal neurons reveal reward-induced inhibition, which weakens during satiation and becomes further attenuated in depression mouse models. Ablating or inhibiting these neurons desensitizes reward devaluation, causes reward intake increase and ultimate obesity, and ameliorates depression, whereas activating the cells sensitizes reward devaluation, suppresses reward consumption, and produces depression-like behaviors. Among various ACC neuron subpopulations, the BLA-projecting subset bidirectionally regulates reward devaluation and depression-like behaviors. Our study thus uncovers a corticoamygdalar circuit that encodes reward devaluation via blunted inhibition and suggests that enhancing inhibition within this circuit may offer a therapeutic approach for treating depression.
Topics: Animals; Mice; Conditioning, Operant; Depression; Reward; Basolateral Nuclear Complex; Satiation
PubMed: 37734380
DOI: 10.1016/j.neuron.2023.08.022 -
Nature Dec 2021The brain is the seat of body weight homeostasis. However, our inability to control the increasing prevalence of obesity highlights a need to look beyond canonical...
The brain is the seat of body weight homeostasis. However, our inability to control the increasing prevalence of obesity highlights a need to look beyond canonical feeding pathways to broaden our understanding of body weight control. Here we used a reverse-translational approach to identify and anatomically, molecularly and functionally characterize a neural ensemble that promotes satiation. Unbiased, task-based functional magnetic resonance imaging revealed marked differences in cerebellar responses to food in people with a genetic disorder characterized by insatiable appetite. Transcriptomic analyses in mice revealed molecularly and topographically -distinct neurons in the anterior deep cerebellar nuclei (aDCN) that are activated by feeding or nutrient infusion in the gut. Selective activation of aDCN neurons substantially decreased food intake by reducing meal size without compensatory changes to metabolic rate. We found that aDCN activity terminates food intake by increasing striatal dopamine levels and attenuating the phasic dopamine response to subsequent food consumption. Our study defines a conserved satiation centre that may represent a novel therapeutic target for the management of excessive eating, and underscores the utility of a 'bedside-to-bench' approach for the identification of neural circuits that influence behaviour.
Topics: Adult; Animals; Appetite Regulation; Body Weight Maintenance; Cerebellar Nuclei; Cerebellum; Cues; Dopamine; Eating; Feeding Behavior; Female; Food; Homeostasis; Humans; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred C57BL; Neostriatum; Neurons; Obesity; Philosophy; Protein Biosynthesis; Reverse Genetics; Satiety Response; Young Adult
PubMed: 34789878
DOI: 10.1038/s41586-021-04143-5 -
United European Gastroenterology Journal Apr 2021Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of...
BACKGROUND
Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis.
METHODS
A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements.
RESULTS
The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable.
CONCLUSIONS AND INFERENCES
A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.
Topics: Abdominal Pain; Consensus; Delphi Technique; Dyspepsia; Endoscopy, Gastrointestinal; Europe; Female; Gastroenterology; Helicobacter Infections; Helicobacter pylori; Humans; Male; Neurology; Postprandial Period; Proton Pump Inhibitors; Quality of Life; Risk Factors; Satiation; Sex Factors; Societies, Medical; Symptom Assessment
PubMed: 33939891
DOI: 10.1002/ueg2.12061