RESUMO
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.
Assuntos
Apetite/fisiologia , Fome/fisiologia , Sede/fisiologia , Animais , Regulação do Apetite/fisiologia , Encéfalo/fisiologia , Comportamento Alimentar/fisiologia , Homeostase/fisiologia , Humanos , Fenômenos Fisiológicos do Sistema Nervoso , Neurônios/fisiologia , Saciação/fisiologia , Sódio/metabolismoRESUMO
The termination of a meal is controlled by dedicated neural circuits in the caudal brainstem. A key challenge is to understand how these circuits transform the sensory signals generated during feeding into dynamic control of behaviour. The caudal nucleus of the solitary tract (cNTS) is the first site in the brain where many meal-related signals are sensed and integrated1-4, but how the cNTS processes ingestive feedback during behaviour is unknown. Here we describe how prolactin-releasing hormone (PRLH) and GCG neurons, two principal cNTS cell types that promote non-aversive satiety, are regulated during ingestion. PRLH neurons showed sustained activation by visceral feedback when nutrients were infused into the stomach, but these sustained responses were substantially reduced during oral consumption. Instead, PRLH neurons shifted to a phasic activity pattern that was time-locked to ingestion and linked to the taste of food. Optogenetic manipulations revealed that PRLH neurons control the duration of seconds-timescale feeding bursts, revealing a mechanism by which orosensory signals feed back to restrain the pace of ingestion. By contrast, GCG neurons were activated by mechanical feedback from the gut, tracked the amount of food consumed and promoted satiety that lasted for tens of minutes. These findings reveal that sequential negative feedback signals from the mouth and gut engage distinct circuits in the caudal brainstem, which in turn control elements of feeding behaviour operating on short and long timescales.
Assuntos
Regulação do Apetite , Tronco Encefálico , Ingestão de Alimentos , Retroalimentação Fisiológica , Alimentos , Saciação , Estômago , Regulação do Apetite/fisiologia , Tronco Encefálico/citologia , Tronco Encefálico/fisiologia , Ingestão de Alimentos/fisiologia , Vias Neurais/citologia , Vias Neurais/fisiologia , Neurônios/metabolismo , Hormônio Liberador de Prolactina/metabolismo , Saciação/fisiologia , Núcleo Solitário/citologia , Núcleo Solitário/fisiologia , Estômago/fisiologia , Paladar/fisiologia , Fatores de Tempo , Animais , CamundongosRESUMO
Ingested food and water stimulate sensory systems in the oropharyngeal and gastrointestinal areas before absorption1,2. These sensory signals modulate brain appetite circuits in a feed-forward manner3-5. Emerging evidence suggests that osmolality sensing in the gut rapidly inhibits thirst neurons upon water intake. Nevertheless, it remains unclear how peripheral sensory neurons detect visceral osmolality changes, and how they modulate thirst. Here we use optical and electrical recording combined with genetic approaches to visualize osmolality responses from sensory ganglion neurons. Gut hypotonic stimuli activate a dedicated vagal population distinct from mechanical-, hypertonic- or nutrient-sensitive neurons. We demonstrate that hypotonic responses are mediated by vagal afferents innervating the hepatic portal area (HPA), through which most water and nutrients are absorbed. Eliminating sensory inputs from this area selectively abolished hypotonic but not mechanical responses in vagal neurons. Recording from forebrain thirst neurons and behavioural analyses show that HPA-derived osmolality signals are required for feed-forward thirst satiation and drinking termination. Notably, HPA-innervating vagal afferents do not sense osmolality itself. Instead, these responses are mediated partly by vasoactive intestinal peptide secreted after water ingestion. Together, our results reveal visceral hypoosmolality as an important vagal sensory modality, and that intestinal osmolality change is translated into hormonal signals to regulate thirst circuit activity through the HPA pathway.
Assuntos
Intestinos , Saciação , Células Receptoras Sensoriais , Sede , Gânglios Sensitivos/citologia , Intestinos/citologia , Intestinos/inervação , Concentração Osmolar , Pressão Osmótica , Saciação/fisiologia , Células Receptoras Sensoriais/citologia , Sede/fisiologia , Nervo Vago/citologia , Nervo Vago/fisiologia , Água/metabolismoRESUMO
Satiation is the process by which eating and drinking reduce appetite. For thirst, oropharyngeal cues have a critical role in driving satiation by reporting to the brain the volume of fluid that has been ingested1-12. By contrast, the mechanisms that relay the osmolarity of ingested fluids remain poorly understood. Here we show that the water and salt content of the gastrointestinal tract are precisely measured and then rapidly communicated to the brain to control drinking behaviour in mice. We demonstrate that this osmosensory signal is necessary and sufficient for satiation during normal drinking, involves the vagus nerve and is transmitted to key forebrain neurons that control thirst and vasopressin secretion. Using microendoscopic imaging, we show that individual neurons compute homeostatic need by integrating this gastrointestinal osmosensory information with oropharyngeal and blood-borne signals. These findings reveal how the fluid homeostasis system monitors the osmolarity of ingested fluids to dynamically control drinking behaviour.
Assuntos
Encéfalo/fisiologia , Ingestão de Líquidos/fisiologia , Trato Gastrointestinal/fisiologia , Neurônios/fisiologia , Saciação/fisiologia , Sede/fisiologia , Animais , Encéfalo/citologia , Feminino , Neurônios GABAérgicos/metabolismo , Trato Gastrointestinal/inervação , Glutamatos/metabolismo , Masculino , Camundongos , Orofaringe/inervação , Orofaringe/fisiologia , Concentração Osmolar , Prosencéfalo/metabolismo , Nervo Vago/fisiologia , Vasopressinas/metabolismoRESUMO
BACKGROUND: Obesity originates from an imbalance between energy intake and expenditure. Changes in energy intake components (satiation, postprandial satiety, emotional eating) and energy expenditure have been linked to obesity and are referred to as obesity phenotypes. We aim to study if these obesity phenotypes have a cumulative effect on body weight and body mass index (BMI). SUBJECT/METHODS: This is a cross-sectional study of adult patients with obesity (BMI > 30 kg/m2) who completed the validated tests to measure the obesity phenotypes. A total of 464 were included in this study. INTERVENTIONS/METHODS: We defined higher calories to fullness during an ad libitum meal as abnormal satiation, accelerated time to half gastric emptying with scintigraphy as abnormal postprandial satiety, higher anxiety score on the Hospital Anxiety and Depression Scale as hedonic eating behavior, and decreased percentage of measured resting energy expenditure as abnormal energy expenditure. The primary analysis was done on the number of phenotypes ( ≤ 1 and ≥ 2) with body weight and BMI using an independent t-test. RESULTS: Our cohort included 464 patients (mean [SD] age 42.0 [10.9] years, 79% females, weight 111.2 [22.9] kg, BMI 38.9 [7.0] kg/m2). There were 294 patients who had ≤ 1 phenotype, and 170 patients with ≥ 2 phenotypes with no baseline demographical differences (i.e., age and sex). Having ≥ 2 phenotypes was associated with higher body weight (115 [25] kg vs. 109 [21] kg; p = 0.004), BMI (40 [8] kg/m2 vs. 38 [7] kg/m2; p = 0.02) and waist (118 [15] cm vs. 115 [13] cm; p = 0.04) and hip (129 [14] cm vs. 125 [13] cm; p = 0.01) circumferences compared to ≤ 1 phenotype. CONCLUSION: Obesity phenotypes are associated with an additive effect on the body weight and BMI. Patients who have multiple obesity phenotypes may require a more aggressive approach to enhance weight loss.
Assuntos
Índice de Massa Corporal , Peso Corporal , Metabolismo Energético , Obesidade , Fenótipo , Humanos , Feminino , Masculino , Obesidade/fisiopatologia , Obesidade/psicologia , Estudos Transversais , Adulto , Peso Corporal/fisiologia , Pessoa de Meia-Idade , Metabolismo Energético/fisiologia , Saciação/fisiologia , Ingestão de Energia/fisiologiaRESUMO
Terminating a meal after achieving satiation is a critical step in maintaining a healthy energy balance. Despite the extensive collection of information over the last few decades regarding the neural mechanisms controlling overall eating, the mechanism underlying different temporal phases of eating behaviors, especially satiation, remains incompletely understood and is typically embedded in studies that measure the total amount of food intake. In this review, we summarize the neural circuits that detect and integrate satiation signals to suppress appetite, from interoceptive sensory inputs to the final motor outputs. Due to the well-established role of cholecystokinin (CCK) in regulating the satiation, we focus on the neural circuits that are involved in regulating the satiation effect caused by CCK. We also discuss several general principles of how these neural circuits control satiation, as well as the limitations of our current understanding of the circuits function. With the application of new techniques involving sophisticated cell-type-specific manipulation and mapping, as well as real-time recordings, it is now possible to gain a better understanding of the mechanisms specifically underlying satiation.
Assuntos
Colecistocinina , Saciação , Saciação/fisiologia , Humanos , Colecistocinina/fisiologia , Animais , Comportamento Alimentar/fisiologia , Ingestão de Alimentos/fisiologia , Vias Neurais/fisiologia , Encéfalo/fisiologia , Regulação do Apetite/fisiologiaRESUMO
Limited evidence is available about the variability of appetitive responses within individuals after an acute bout of exercise. The present study aimed to assess the consistency and individual variability of post-exercise appetitive responses in healthy individuals. Twenty participants (10 females, 23.9 ± 4.1 years, 22.5 ± 2.0 kg m-2) joined the laboratory to perform four sessions separated by a minimum of 5 days: i) a control session with a rest period before and an ad libitum lunch (REST), and ii) three identical exercise sessions (EX) with a 30-min moderate-intensity (60-70% of predicted maximal heart rate) walking bout ending 25 min before the ad libitum lunch. Subjective appetite sensations were assessed before and after the meal at regular intervals, and satiety quotients were calculated. Food reward was assessed by the Leeds Food Preference Questionnaire before and after lunch. For each EX session, the difference with the REST session was calculated (Δ = EX - REST). Energy and macronutrient intake were consistent in response to exercise (all intraclass correlation coefficients (ICC) > 0.8) while results showed that post-exercise subjective appetite sensations and satiety quotients varied across the three EX sessions (almost all ICC < 0.7). Food reward was overall consistent in response to exercise before the test meal but not after. When considering the changes (Δ), the results showed no or poor consistency for most of the appetitive outcomes. To conclude, energy and macronutrient intake, as well as pre-meal food reward, are consistent after exercise in healthy individuals, while subjective appetite sensations are not stable within individuals across the sessions. Regarding the variations from REST to EX sessions, the results suggest that the individual changes observed are only random day-to-day variations.
Assuntos
Apetite , Ingestão de Energia , Exercício Físico , Preferências Alimentares , Recompensa , Humanos , Feminino , Masculino , Apetite/fisiologia , Adulto , Exercício Físico/fisiologia , Exercício Físico/psicologia , Adulto Jovem , Ingestão de Energia/fisiologia , Preferências Alimentares/psicologia , Preferências Alimentares/fisiologia , Saciação/fisiologia , Nutrientes , Inquéritos e QuestionáriosRESUMO
Chemogenetic activation of oxytocin receptor-expressing neurons in the parabrachial nucleus (OxtrPBN neurons) acts as a satiation signal for water. In this research, we investigated the effect of activating OxtrPBN neurons on satiation for different types of fluids. Chemogenetic activation of OxtrPBN neurons in male and female transgenic OxtrCre mice robustly suppressed the rapid, initial (15-min) intake of several solutions after dehydration: water, sucrose, ethanol and saccharin, but only slightly decreased intake of Ensure®, a highly caloric solution (1 kcal/mL; containing 3.72 g protein, 3.27 g fat, 13.42 g carbohydrates, and 1.01 g dietary fibre per 100 mL). OxtrPBN neuron activation also suppressed cumulative, longer-term (2-h) intake of lower caloric, less palatable solutions, but not highly caloric, palatable solutions. These results suggest that OxtrPBN neurons predominantly control initial fluid-satiation responses after rehydration, but not longer-term intake of highly caloric, palatable solutions. The suppression of fluid intake was not because of anxiogenesis, but because OxtrPBN neuron activation decreased anxiety-like behaviour. To investigate the role of different PBN subdivisions on the intake of different solutions, we examined FOS as a proxy marker of PBN neuron activation. Different PBN subdivisions were activated by different solutions: the dorsolateral PBN similarly by all fluids; the external lateral PBN by caloric but not non-caloric solutions; and the central lateral PBN primarily by highly palatable solutions, suggesting PBN subdivisions regulate different aspects of fluid intake. To explore the possible mechanisms underlying the minimal suppression of Ensure® after OxtrPBN neuron activation, we demonstrated in in vitro slice recordings that the feeding-associated agouti-related peptide (AgRP) inhibited OxtrPBN neuron firing in a concentration-related manner, suggesting possible inhibition by feeding-related neurocircuitry of fluid satiation neurocircuitry. Overall, this research suggests that although palatable beverages like sucrose- and ethanol-containing beverages activate fluid satiation signals encoded by OxtrPBN neurons, these neurons can be inhibited by hunger-related signals (agouti-related peptide, AgRP), which may explain why these fluids are often consumed in excess of what is required for fluid satiation.
Assuntos
Núcleos Parabraquiais , Camundongos , Masculino , Feminino , Animais , Núcleos Parabraquiais/metabolismo , Proteína Relacionada com Agouti/metabolismo , Proteína Relacionada com Agouti/farmacologia , Saciação/fisiologia , Água/metabolismo , Sacarose/farmacologia , Etanol/farmacologiaRESUMO
PURPOSE: Early satiety has been identified as one of the mechanisms that may explain the beneficial effects of nuts for reducing obesity. This study compared postprandial changes in appetite-regulating hormones and self-reported appetite ratings after consuming almonds (AL, 15% of energy requirement) or an isocaloric carbohydrate-rich snack bar (SB). METHODS: This is a sub-analysis of baseline assessments of a larger parallel-arm randomised controlled trial in overweight and obese (Body Mass Index 27.5-34.9 kg/m2) adults (25-65 years). After an overnight fast, 140 participants consumed a randomly allocated snack (AL [n = 68] or SB [n = 72]). Appetite-regulating hormones and self-reported appetite sensations, measured using visual analogue scales, were assessed immediately before snack food consumption, and at 30, 60, 90 and 120 min following snack consumption. A sub-set of participants (AL, n = 49; SB, n = 48) then consumed a meal challenge buffet ad libitum to assess subsequent energy intake. An additional appetite rating assessment was administered post buffet at 150 min. RESULTS: Postprandial C-peptide area under the curve (AUC) response was 47% smaller with AL compared to SB (p < 0.001). Glucose-dependent insulinotropic polypeptide, glucagon and pancreatic polypeptide AUC responses were larger with AL compared to SB (18%, p = 0.005; 39% p < 0.001; 45% p < 0.001 respectively). Cholecystokinin, ghrelin, glucagon-like peptide-1, leptin and polypeptide YY AUCs were not different between groups. Self-reported appetite ratings and energy intake following the buffet did not differ between groups. CONCLUSION: More favourable appetite-regulating hormone responses to AL did not translate into better self-reported appetite or reduced short-term energy consumption. Future studies should investigate implications for longer term appetite regulation. ANZCTR REFERENCE NUMBER: ACTRN12618001861246 2018.
Assuntos
Apetite , Prunus dulcis , Adulto , Humanos , Apetite/fisiologia , Lanches , Autorrelato , Insulina , Saciação/fisiologia , Grelina , Obesidade , Ingestão de Energia , Sensação , Carboidratos , Período Pós-PrandialRESUMO
OBJECTIVE: Gastrointestinal symptoms, particularly postprandial fullness, are frequently reported in eating disorders. Limited data exist evaluating how these symptoms change in response to outpatient psychological treatment. The current study sought to describe the course of postprandial fullness and early satiation across psychological treatment for adults with bulimia nervosa and related other specified feeding or eating disorders and to test if anxiety moderates treatment response. METHODS: Secondary data analysis was conducted on questionnaire data provided by 30 individuals (80% white, M(SD)age = 31.43(13.44) years; 90% female) throughout treatment and six-month follow-up in a pilot trial comparing mindfulness and acceptance-based treatment with cognitive-behavioral therapy for bulimia nervosa. Participants completed items from the Rome IV Diagnostic Questionnaire for Adult Functional Gastrointestinal Disorders and the State Trait Anxiety Inventory. RESULTS: Postprandial fullness and early satiation both significantly decreased over time (ds = 1.23-1.54; p's < .001). Baseline trait anxiety moderated this outcome, such that greater decreases were observed for those with higher baseline anxiety (p = .02). DISCUSSION: Results extend prior work in inpatient samples by providing preliminary data that postprandial fullness and early satiation decrease with outpatient psychological treatment for bulimia nervosa. Baseline anxiety moderated this effect for postprandial fullness. Future work should replicate findings in a larger sample and test anxiety as a mechanism underlying postprandial fullness in eating disorders. PUBLIC SIGNIFICANCE: The current study found that common gastrointestinal symptoms (postprandial fullness and early satiation) decrease over the course of outpatient psychotherapy for adults with full and subthreshold bulimia nervosa. Postprandial fullness decreased more across time for those high in anxiety.
Assuntos
Anorexia Nervosa , Bulimia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Adulto , Humanos , Feminino , Masculino , Bulimia Nervosa/psicologia , Dados Preliminares , Ansiedade/terapia , Saciação/fisiologiaRESUMO
From a public health perspective, much of the interest in the relationship between exercise and appetite rests on the implications for energy balance and obesity. Energy balance reflects a dynamic 2-way interaction between energy expenditure (EE) and energy intake (EI). Physical activity and exercise, and appetite are the behavioural components of EE and EI, respectively. Beyond EE, exercise is a powerful and complex physiological stimulus acting on several bodily systems. There are multiple effects of frequent and prolonged exercise on appetite which include inter alia an increase in fasting hunger, an enhancement of post-prandial satiety, a modulation of the hedonic responses to food and improvements in eating behaviour traits. These lead to variable adjustments in EI and in a reduction in the susceptibility to overconsumption. Frequent and prolonged physical activity and exercise behaviour can strengthen and sensitise the appetite control system, whilst physical inactivity and sedentariness (low level of EE) fails to downregulate EI and can permit overconsumption. Not all of the effects of exercise operate uniformly to drive appetite in the same direction. The complexity of the interaction between EE and EI means that the effects of prolonged exercise are characterised by substantial individual heterogeneity. This leads to variable effects on energy balance and body mass.
Assuntos
Regulação do Apetite , Apetite , Humanos , Apetite/fisiologia , Obesidade , Saciação/fisiologia , Comportamento Alimentar , Ingestão de Energia/fisiologia , Metabolismo Energético/fisiologiaRESUMO
Older adults are advised to increase their protein intake to maintain their muscle mass. However, protein is considered the most satiating macronutrient and this recommendation may cause a decrease in total energy intake. To date, satiety studies comparing all three macronutrients have been undertaken in young adults, and it is unclear if the same response is seen in older adults. The objective of this study was to compare the effect of preloads high in protein, fat, and carbohydrate but equal in energy (â¼300 kcal) and volume (250 ml) on energy intake, perceived appetite, and gastric emptying in younger and older adults. Twenty older and 20 younger adults completed a single-blinded randomised crossover trial involving three study visits. Participants consumed a standard breakfast, followed by a preload milkshake high in either carbohydrate, fat, or protein. Three hours after the preload, participants were offered an ad libitum meal to assess food intake. Visual analogue scales were used to measure perceived appetite and gastric emptying was measured via the 13C-octanoic acid breath test. There was no significant effect of preload type or age on energy intake either at the ad libitum meal, self-recorded food intake for the rest of the test day or subjective appetite ratings. There was a significant effect of preload type on gastric emptying latency phase and ascension time, and an effect of age on gastric emptying latency and lag phase such that older adults had faster emptying. In conclusion, energy intake, and perceived appetite were not affected by macronutrient content of the preloads in both younger and older adults, but gastric emptying times differed.
Assuntos
Apetite , Saciação , Adulto Jovem , Humanos , Idoso , Saciação/fisiologia , Apetite/fisiologia , Ingestão de Energia , Nutrientes , Ingestão de Alimentos , Carboidratos/farmacologia , Estudos Cross-OverRESUMO
While obesity remains a pressing issue, the wider population continues to be exposed to more digital food content than ever before. Much research has demonstrated the priming effect of visual food content, i.e., exposure to food cues increasing appetite and food intake. In contrast, some recent research points out that repeated imagined consumption can facilitate satiate and decrease food intake. Such findings have been suggested as potential remedies to excessive food cue exposure. However, the practically limitless variety of digital food content available today may undermine satiation attempts. The present work aims to replicate and extend prior findings by introducing a within-subjects baseline comparison, disentangling general and (sensory-) specific eating desires, as well as considering the moderating influence of visual and flavour stimulus variety. Three online studies (n = 1149 total) manipulated food colour and flavour variety and reproducibly revealed a non-linear dose-response pattern of imagined eating: 3 repetitions primed, while 30 repetitions satiated. Priming appeared to be specific to the taste of the exposed stimulus, and satiation, contrary to prior literature, appeared to be more general. Neither colour nor flavour variety reliably moderated any of the responses. Therefore, the results suggest that a more pronounced variety may be required to alter imagery-induced satiation.
Assuntos
Ingestão de Alimentos , Saciação , Humanos , Ingestão de Alimentos/fisiologia , Saciação/fisiologia , Apetite/fisiologia , Alimentos , Preferências Alimentares/fisiologia , Paladar/fisiologia , Aromatizantes , Resposta de Saciedade , Ingestão de EnergiaRESUMO
This study aimed to evaluate the short-term effect of a common bean baked snack (CBBS) and cooked bean consumption on energy intake, satiety, glycemic response, and palatability in subjects with normal weight (Study 1) and overweight (Study 2) and to determine the glycemic index of CBBS (Study 3). For studies 1 and 2, satiety and glycemic response were measured over 45 min after consuming CBBS, cooked beans or white bread preload, and energy intake at an ad libitum test meal was calculated. Energy intake remained similar after consuming the three preloads in both studies. Compared to white bread, CBBS consumption increased fullness by 52% in subjects with normal weight but not in those with overweight. The CBBS calculated glycemic index was considered low (42). Consumption of low glycemic index CBBS increased satiety in adults with a normal weight. Long-term trials assessing the effects on body weight management are necessary.
Assuntos
Índice Glicêmico , Phaseolus , Humanos , Adulto , Sobrepeso , Lanches , Estudos Cross-Over , Glicemia , Saciação/fisiologia , Ingestão de EnergiaRESUMO
The prevalence of alcohol consumption and obesity continues to increase. The aim of this literature review was to give an overview of the association between these two health and socioeconomic problems. Ethanol must be considered as an orexigenic molecule, acting on the cerebral regulation of hunger and satiety and on the mesolimbic reward system. Moreover, studies showed that alcohol blocks the fatty acid beta oxidation, promoting the storage of lipids. Observational and experimental studies struggle to find a solid correlation between the two entities, but they have several biases and limitations. Experts agree to consider ethanol ingestion as a potential contributing factor of the higher obesity rates observed in the last decades.
Les prévalences de la consommation d'alcool et de l'obésité ne cessent d'augmenter. L'objectif de cette revue de la littérature est de donner un aperçu de l'association entre ces deux problématiques sanitaires et socio-économiques. L'éthanol, agissant sur la régulation cérébrale de la faim et de la satiété ainsi que sur le système mésolimbique de la récompense, est à considérer comme une substance orexigène. En outre, il bloque la bêta-oxydation des lipides, prédisposant à leur stockage. Malgré des évidences scientifiques discordantes, qui sont cependant conditionnées par des biais et limitations, les experts sont d'accord de considérer la consommation de boissons alcoolisées comme un probable facteur contribuant à l'incrémentation du taux d'obésité observé lors des dernières décennies.
Assuntos
Consumo de Bebidas Alcoólicas , Etanol , Humanos , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Fome/fisiologia , Saciação/fisiologia , Obesidade/epidemiologiaRESUMO
INTRODUCTION: Cannabidiol (CBD), a CBR2 agonist with limited psychic effects, antagonizes CB1/CB2 receptors. Allelic variation CNR1 (gene for CBR1) rs806378 and FAAH rs324420 were associated with altered gut motility and sensation. This study aimed to compare the pharmacodynamics and clinical effects of a 4-week treatment with pharmaceutical-grade CBD vs placebo and assess the interactions of FAAH and CNR1 gene variants on the effects of CBD in patients with functional dyspepsia (FD). METHODS: We performed a randomized, double-blinded, placebo-controlled (1:1 ratio) study of CBD b.i.d. (20 mg/kg/d according to the US Food and Drug Administration escalation guidance) in FD patients with nondelayed gastric emptying (GE) at baseline. Symptoms were assessed by validated daily symptom diary (0-4 scale for upper abdominal pain, nausea, and bloating), weekly assessment of adequate relief, Leuven Postprandial Distress Scale (8 symptoms, adjectival scores rated 0-4 for severity), and quality of life (Short-Form Nepean Dyspepsia Index [average of 10 dimensions each on a 5-point scale]). After the 4-week treatment, all patients underwent measurements of GE of solids, gastric volumes, and Ensure nutrient satiation test. Statistical analysis compared 2 treatments for all endpoints and the effects of CBD in association with FAAH rs324420 and CNR1 rs806378. RESULTS: CBD and placebo effects on physiological functions and patient response outcomes were not significantly different. There were borderline CBD treatment-by-genotype interactions: rs806378 CNR1 with Leuven Postprandial Distress Scale ( P = 0.06) and GE solids ( P = 0.12). DISCUSSION: Approved doses of CBD used off-label do not relieve FD with normal baseline GE of solids or alter gastric motor functions and satiation. CBD treatment-by-gene interactions suggest potential benefits for postprandial distress with CNR1 rs806378 T allele.
Assuntos
Canabidiol , Dispepsia , Esvaziamento Gástrico , Amidoidrolases/genética , Canabidiol/uso terapêutico , Método Duplo-Cego , Dispepsia/tratamento farmacológico , Dispepsia/genética , Humanos , Qualidade de Vida , Receptor CB1 de Canabinoide/genética , Saciação/fisiologiaRESUMO
BACKGROUND: Satiation is a key component of food intake regulation as it brings an eating episode to an end. The effect of sex on satiation measurement has not been characterized. OBJECTIVE: To assess the effects of biological variables on satiation. DESIGN: Retrospective cohort study. We included 959 participants (mean age 39 [SD 12] years; 70.7% female, and BMI 33 kg/m2 [8]) who had measurements of satiation with a nutrient-drink test to assess volume to fullness (VTF) and maximum tolerated volume (MTV), and/or an ad libitum meal test to assess calories consumed to fullness (CTF). We performed univariate and multiple regression analyses to estimate the contribution of sex to VTF, MTV, and CTF, compared to other biological variables, such as age, weight, height, BMI, waist-to-hip circumference (W/H), and lean mass percentage (LM%), that are known to affect these parameters. RESULTS: Females had higher BMI, W/H, and LM%. VTF, MTV, and CTF were lower in females: 704 [323] vs. 783 [328] mL, p = 0.001; 1226 [384] vs. 1419 [410] mL, p < 0.001; and 871 [291] vs. 1086 [326] kcal, p < 0.001; respectively. Sex was a strong and independent predictor of VTF, MTF and CTF: parameter estimate [PE] = -80.8, p = 0.006; PE = -124.2, p = 0.0007; and PE = -110, p = 0.001; respectively. CONCLUSIONS: Sex has a strong effect on satiation measured by VTF, MTV, and CTF, even after adjusting for other biological factors known to affect these parameters. Females seem to integrate intra-meal inhibition signals to consume fewer calories unrelated to body size or composition. CLINICAL TRIAL REGISTRATION: None.
Assuntos
Obesidade , Saciação , Humanos , Feminino , Adulto , Masculino , Estudos Retrospectivos , Saciação/fisiologia , Ingestão de Energia/fisiologia , Refeições , Ingestão de AlimentosRESUMO
BACKGROUND/OBJECTIVES: Disrupted leptin signaling in vagal afferent neurons contributes to hyperphagia and obesity. Thus, we tested the hypothesis that intrinsic negative regulators of leptin signaling, suppressor of cytokine signaling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) underlie dysfunctional leptin-mediated vagal afferent satiety signaling during obesity. METHODS: Experiments were performed on standard chow-fed control mice, high-fat fed (HFF), or low-fat fed (LFF) mice. SOCS3 and PTP1B expression were quantified using western blot and quantitative PCR. Nodose ganglion neuronal excitability and jejunal afferent sensitivity were measured by patch clamp and extracellular afferent recordings, respectively. RESULTS: Increased expression of SOCS3 and PTP1B were observed in the jejunum of HFF mice. Prolonged incubation with leptin attenuated nodose ganglion neuronal excitability, and this effect was reversed by inhibition of SOCS3. Leptin potentiated jejunal afferent nerve responses to CCK in LFF mice but decreased them in HFF mice. Inhibition of SOCS3 restored impaired vagal afferent neuronal excitability and afferent nerve responses to satiety mediators during obesity. Two-pore domain K+ channel (K2P) conductance and nitric oxide (NO) production that we previously demonstrated were elevated during obesity were decreased by inhibitions of SOCS3 or PTP1B. CONCLUSIONS: This study suggests that obesity impairs vagal afferent sensitivity via SOCS3 and PTP1B, likely as a consequence of obesity-induced hyperleptinemia. The mechanisms underlying leptin resistance appear also to cause a more global impairment of satiety-related vagal afferent responsiveness.
Assuntos
Leptina , Obesidade , Animais , Leptina/metabolismo , Camundongos , Gânglio Nodoso/metabolismo , Obesidade/metabolismo , Saciação/fisiologia , Nervo Vago/fisiologiaRESUMO
Peripheral glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK) are secreted from enteroendocrine cells, and their plasma concentrations increase in response to eating. While the satiating effect of gut-derived CCK on food-intake control is well documented, the effect of peripheral GLP-1 is less clear. There is evidence that native GLP-1 can inhibit food intake only in the fed state but not in the fasting state. We therefore hypothesized that other gut peptides released during a meal might influence the subsequent effect of endogenous GLP-1 and investigated whether CCK could do so. We found that intraperitoneal injection of CCK in food-restricted mice inhibited food intake during the first 30-minute segment of a 1-hour session of ad libitum chow intake and that mice compensated by increasing their intake during the second half of the session. Importantly, this compensatory behaviour was abolished by an intraperitoneal injection of GLP-1 administered following an intraperitoneal injection of CCK and prior to the 1-hour session. In vivo activation of the free fatty acid 1 (FFA1) receptor with orally administered TAK875 increased plasma CCK concentration and, consistent with the effect of exogenous CCK, we found that prior oral administration of TAK875 increased the eating inhibitory effect of peripherally administered GLP-1. To examine the role of the vagus nerve in this effect, we utilized a saporin-based lesioning procedure to selectively ablate the CCK receptor-expressing gastrointestinal vagal afferent neurones (VANs). We found that the combined anorectic effect of TAK875 and GLP-1 was significantly attenuated in the absence of CCK receptor expressing VANs. Taken together, our results indicate that endogenous CCK interacts with GLP-1 to promote satiation and that activation of the FFA1 receptor can initiate this interaction by stimulating the release of CCK.
Assuntos
Colecistocinina , Peptídeo 1 Semelhante ao Glucagon , Animais , Ingestão de Alimentos , Humanos , Camundongos , Receptores da Colecistocinina , Saciação/fisiologia , Nervo Vago/fisiologiaRESUMO
Memory processes may have several roles in appetite regulation. Here we examine one such role, derived from the animal literature, in which satiety cues lead to the inhibition of rewarding food-related memories. We tested this idea over three studies (n's of 58, 67, 50 respectively), by presenting participants with visual or verbal food cues, and asking them to describe what these foods were like to eat. This recollection task was undertaken hungry and sated. The resulting recollections were then coded and contrasted across state. Irrespective of state, participants took the same time to make their recollections, they were of similar length and included the same amount of sensory detail and affective content. However, in all three studies, sated recollections tended to include more reports about how filling a food would be. This increase in reports of food fillingness across state, was significantly correlated with increases in reports of stomach distension across state. While these results are consistent with the operation of memory inhibition, a further possibility is considered, whereby interoceptive satiety cues are integrated into food-related recollections (but not other recollections) to form a memory-inteorception-combination, thereby drawing attention to the consequences of eating when sated.