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Frontiers in Endocrinology 2021The peptide hormone leptin regulates food intake, body mass, and reproductive function and plays a role in fetal growth, proinflammatory immune responses, angiogenesis... (Review)
Review
The peptide hormone leptin regulates food intake, body mass, and reproductive function and plays a role in fetal growth, proinflammatory immune responses, angiogenesis and lipolysis. Leptin is a product of the obese () gene and, following synthesis and secretion from fat cells in white adipose tissue, binds to and activates its cognate receptor, the leptin receptor (LEP-R). LEP-R distribution facilitates leptin's pleiotropic effects, playing a crucial role in regulating body mass a negative feedback mechanism between adipose tissue and the hypothalamus. Leptin resistance is characterized by reduced satiety, over-consumption of nutrients, and increased total body mass. Often this leads to obesity, which reduces the effectiveness of using exogenous leptin as a therapeutic agent. Thus, combining leptin therapies with leptin sensitizers may help overcome such resistance and, consequently, obesity. This review examines recent data obtained from human and animal studies related to leptin, its role in obesity, and its usefulness in obesity treatment.
Topics: Animals; Energy Metabolism; Humans; Hypothalamus; Leptin; Obesity; Risk Factors; Satiety Response; Signal Transduction
PubMed: 34084149
DOI: 10.3389/fendo.2021.585887 -
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 -
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 -
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 -
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 -
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 -
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 -
Journal of Obesity & Metabolic Syndrome Sep 2020Several clinical trials have found that consuming more protein than the recommended dietary allowance not only reduces body weight (BW), but also enhances body... (Review)
Review
Several clinical trials have found that consuming more protein than the recommended dietary allowance not only reduces body weight (BW), but also enhances body composition by decreasing fat mass while preserving fat-free mass (FFM) in both low-calorie and standard-calorie diets. Fairly long-term clinical trials of 6-12 months reported that a high-protein diet (HPD) provides weight-loss effects and can prevent weight regain after weight loss. HPD has not been reported to have adverse effects on health in terms of bone density or renal function in healthy adults. Among gut-derived hormones, glucagon-like peptide-1, cholecystokinin, and peptide tyrosine-tyrosine reduce appetite, while ghrelin enhances appetite. HPD increases these anorexigenic hormone levels while decreasing orexigenic hormone levels, resulting in increased satiety signaling and, eventually, reduced food intake. Additionally, elevated diet-induced thermogenesis (DIT), increased blood amino acid concentration, increased hepatic gluconeogenesis, and increased ketogenesis caused by higher dietary protein contribute to increased satiety. The mechanism by which HPD increases energy expenditure involves two aspects: first, proteins have a markedly higher DIT than carbohydrates and fats. Second, protein intake prevents a decrease in FFM, which helps maintain resting energy expenditure despite weight loss. In conclusion, HPD is an effective and safe tool for weight reduction that can prevent obesity and obesity-related diseases. However, long-term clinical trials spanning more than 12 months should be conducted to further substantiate HPD effects.
PubMed: 32699189
DOI: 10.7570/jomes20028 -
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 -
Obesity (Silver Spring, Md.) Apr 2021Little is known about the predictors of response to obesity interventions.
OBJECTIVE
Little is known about the predictors of response to obesity interventions.
METHODS
In 450 participants with obesity, body composition, resting energy expenditure, satiety, satiation, eating behavior, affect, and physical activity were measured by validated studies and questionnaires. These variables were used to classify obesity phenotypes. Subsequently, in a 12-month, pragmatic, real-world trial performed in a weight management center, 312 patients were randomly assigned to phenotype-guided treatment or non-phenotype-guided treatment with antiobesity medications: phentermine, phentermine/topiramate, bupropion/naltrexone, lorcaserin, and liraglutide. The primary outcome was weight loss at 12 months.
RESULTS
Four phenotypes of obesity were identified in 383 of 450 participants (85%): hungry brain (abnormal satiation), emotional hunger (hedonic eating), hungry gut (abnormal satiety), and slow burn (decreased metabolic rate). In 15% of participants, no phenotype was identified. Two or more phenotypes were identified in 27% of patients. In the pragmatic clinical trial, the phenotype-guided approach was associated with 1.75-fold greater weight loss after 12 months with mean weight loss of 15.9% compared with 9.0% in the non-phenotype-guided group (difference -6.9% [95% CI -9.4% to -4.5%], P < 0.001), and the proportion of patients who lost >10% at 12 months was 79% in the phenotype-guided group compared with 34% with non-phenotype-guided treatment group.
CONCLUSIONS
Biological and behavioral phenotypes elucidate human obesity heterogeneity and can be targeted pharmacologically to enhance weight loss.
Topics: Anti-Obesity Agents; Clinical Trials as Topic; Female; Humans; Male; Obesity; Precision Medicine; Weight Loss
PubMed: 33759389
DOI: 10.1002/oby.23120