RESUMEN
During infection, animals exhibit adaptive changes in physiology and behaviour aimed at increasing survival. Although many causes of infection exist, they trigger similar stereotyped symptoms such as fever, warmth-seeking, loss of appetite and fatigue1,2. Yet exactly how the nervous system alters body temperature and triggers sickness behaviours to coordinate responses to infection remains unknown. Here we identify a previously uncharacterized population of neurons in the ventral medial preoptic area (VMPO) of the hypothalamus that are activated after sickness induced by lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid. These neurons are crucial for generating a fever response and other sickness symptoms such as warmth-seeking and loss of appetite. Single-nucleus RNA-sequencing and multiplexed error-robust fluorescence in situ hybridization uncovered the identity and distribution of LPS-activated VMPO (VMPOLPS) neurons and non-neuronal cells. Gene expression and electrophysiological measurements implicate a paracrine mechanism in which the release of immune signals by non-neuronal cells during infection activates nearby VMPOLPS neurons. Finally, we show that VMPOLPS neurons exert a broad influence on the activity of brain areas associated with behavioural and homeostatic functions and are synaptically and functionally connected to circuit nodes controlling body temperature and appetite. Together, these results uncover VMPOLPS neurons as a control hub that integrates immune signals to orchestrate multiple sickness symptoms in response to infection.
Asunto(s)
Apetito , Fiebre , Infecciones , Neuronas , Área Preóptica , Animales , Apetito/efectos de los fármacos , Depresores del Apetito/farmacología , Fiebre/inducido químicamente , Fiebre/fisiopatología , Hibridación Fluorescente in Situ , Infecciones/inducido químicamente , Infecciones/fisiopatología , Lipopolisacáridos , Neuronas/efectos de los fármacos , Comunicación Paracrina , Poli I-C , Área Preóptica/citología , Área Preóptica/efectos de los fármacos , Área Preóptica/fisiologíaRESUMEN
The mechanism connecting gut microbiota to appetite regulation is not yet fully understood. This study identifies specific microbial community and metabolites that may influence appetite regulation. In the initial phase of the study, mice were administered a broad-spectrum antibiotic cocktail (ABX) for 10 days. The treatment significantly reduced gut microbes and disrupted the metabolism of arginine and tryptophan. Consequently, ABX-treated mice demonstrated a notable reduction in feed consumption. The hypothalamic expression levels of CART and POMC, two key anorexigenic factors, were significantly increased, while orexigenic factors, such as NPY and AGRP, were decreased. Notably, the levels of appetite-suppressing hormone cholecystokinin in the blood were significantly elevated. In the second phase, control mice were maintained, while the ABX-treated mice received saline, probiotics, and short-chain fatty acids (SCFAs) for an additional 10 days to restore their gut microbiota. The microbiota reconstructed by probiotic and SCFA treatments were quite similar, while microbiota of the naturally recovering mice demonstrated greater resemblance to that of the control mice. Notably, the abundance of Akkermansia and Bacteroides genera significantly increased in the reconstructed microbiota. Moreover, microbiota reconstruction corrected the disrupted arginine and tryptophan metabolism and the abnormal peripheral hormone levels caused by ABX treatment. Among the groups, SCFA-treated mice had the highest feed intake and NPY expression. Our findings indicate that gut microbes, especially Akkermansia, regulate arginine and tryptophan metabolism, thereby influencing appetite through the microbe-gut-brain axis.
Asunto(s)
Microbioma Gastrointestinal , Metaboloma , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Masculino , Ratones Endogámicos C57BL , Antibacterianos/farmacología , Triptófano/metabolismo , Apetito/efectos de los fármacos , Probióticos/farmacología , Arginina/farmacología , Arginina/metabolismo , Hipotálamo/metabolismo , Regulación del Apetito/fisiología , Ácidos Grasos Volátiles/metabolismoAsunto(s)
Apetito , Obesidad , Humanos , Animales , Apetito/efectos de los fármacos , Obesidad/tratamiento farmacológico , Ratones , Fármacos Antiobesidad/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Modafinilo/farmacología , Modafinilo/uso terapéutico , Vías Nerviosas/efectos de los fármacosRESUMEN
Most studies on fat appetite have focused on long-chain triglycerides (LCTs) due to their obesogenic properties. Medium-chain triglycerides (MCTs), conversely, exhibit antiobesogenic effects; however, the regulation of MCT intake remains elusive. Here, we demonstrate that mice can distinguish between MCTs and LCTs, and the specific appetite for MCTs is governed by hepatic ß-oxidation. We generated liver-specific medium-chain acyl-CoA dehydrogenase (MCAD)-deficient (MCADL-/-) mice and analyzed their preference for MCT and LCT solutions using glyceryl trioctanoate (C8-TG), glyceryl tridecanoate (C10-TG), corn oil, and lard oil in two-bottle choice tests conducted over 8 days. In addition, we used lick microstructure analyses to evaluate the palatability and appetite for MCT and LCT solutions. Finally, we measured the expression levels of genes associated with fat ingestion (Galanin, Qrfp, and Nmu) in the hypothalamus 2 h after oral gavage of fat. Compared with control mice, MCADL-/- mice exhibited a significantly reduced preference for MCT solutions, with no alteration in the preference for LCTs. Lick analysis revealed that MCADL-/- mice displayed a significantly decreased appetite for MCT solutions only while the palatability of both MCT and LCT solutions remained unaffected. Hypothalamic Galanin expression in control mice was elevated by oral gavage of C8-TG but not by LCTs, and this response was abrogated in MCADL-/- mice. In summary, our data suggest that hepatic ß-oxidation is required for MCT-specific appetite but not for LCT-specific appetite. The induction of hypothalamic galanin upon MCT ingestion, dependent on hepatic ß-oxidation, could be involved in the regulation of MCT-specific appetite.NEW & NOTEWORTHY Whether and how medium-chain triglyceride (MCT) intake is regulated remains unknown. Here, we showed that mice can discriminate between MCTs and LCTs. Hepatic ß-oxidation participates in MCT-specific appetite, and hypothalamic galanin may be one of the factors that regulate MCT intake. Because of the antiobesity effects of MCTs, studying MCT-specific appetite may help combat obesity by promoting the intake of MCTs instead of LCTs.
Asunto(s)
Acil-CoA Deshidrogenasa , Apetito , Ácidos Grasos , Hígado , Ratones Noqueados , Oxidación-Reducción , Triglicéridos , Animales , Triglicéridos/metabolismo , Ratones , Oxidación-Reducción/efectos de los fármacos , Hígado/metabolismo , Hígado/efectos de los fármacos , Masculino , Ácidos Grasos/metabolismo , Apetito/efectos de los fármacos , Apetito/fisiología , Acil-CoA Deshidrogenasa/metabolismo , Acil-CoA Deshidrogenasa/genética , Ratones Endogámicos C57BL , Hipotálamo/metabolismo , Hipotálamo/efectos de los fármacosRESUMEN
This study assessed postprandial plasma aminoacidemia, glycemia, insulinemia and appetite responses to ingestion of a novel salmon-derived protein peptide (Salmon PP) compared with milk protein isolate (Milk PI). In a randomised, participant-blind crossover design, eleven healthy adults (M = 5, F = 6; mean ± sd age: 22 ± 3 years; BMI: 24 ± 3 kg/m2) ingested 0·3 g/kg/body mass of Salmon PP or Milk PI. Arterialised blood samples were collected whilst fasted and over a 240-min postprandial period. Appetite sensations were measured via visual analogue scales. An ad libitum buffet-style test meal was administered after each trial. The incremental AUC (iAUC) plasma essential amino acid (EAA) response was similar between Salmon PP and Milk PI. The iAUC plasma leucine response was significantly greater following Milk PI ingestion (P < 0·001), whereas temporal and iAUC plasma total amino acid (P = 0·001), non-essential amino acid (P = 0·002), glycine (P = 0·0025) and hydroxyproline (P < 0·001) responses were greater following Salmon PP ingestion. Plasma insulin increased similarly above post-absorptive values following Salmon PP and Milk PI ingestion, whilst plasma glucose was largely unaltered. Indices of appetite were similarly altered following Salmon PP and Milk PI ingestion, and total energy and macronutrient intake during the ad libitum meal was similar between Salmon PP and Milk PI. The postprandial plasma EAA, glycine, proline and hydroxyproline response to Salmon PP ingestion suggest this novel protein source could support muscle and possibly connective tissue adaptive remodelling, which warrants further investigation, particularly as the plasma leucine response to Salmon PP ingestion was inferior to Milk PI.
Asunto(s)
Aminoácidos , Apetito , Glucemia , Estudios Cruzados , Insulina , Periodo Posprandial , Salmón , Humanos , Femenino , Animales , Adulto Joven , Apetito/efectos de los fármacos , Apetito/fisiología , Masculino , Aminoácidos/sangre , Adulto , Glucemia/metabolismo , Glucemia/análisis , Insulina/sangre , Proteínas de Peces/sangre , Proteínas de la Leche/farmacología , Péptidos/sangre , Proteínas en la Dieta/administración & dosificaciónRESUMEN
High (free) sugar intakes can increase self-reported energy intake and are associated with unfavourable cardiometabolic health. However, sugar source may modulate the effects of sugars due to several mechanisms including the food matrix. The aim of this review was to assess the current state of evidence in relation to food source effects on the physiological responses to dietary sugars in humans relevant to cardiometabolic health. An additional aim was to review potential mechanisms by which food sources may influence such responses. Evidence from meta-analyses of controlled intervention trials was used to establish the balance of evidence relating to the addition of sugars to the diet from sugar-sweetened beverages, fruit juice, honey and whole fruit on cardiometabolic outcomes. Subsequently, studies which have directly compared whole fruit with fruit juices, or variants of fruit juices, were discussed. In summary, the sources of sugars can impact physiological responses, with differences in glycaemic control, blood pressure, inflammation, and acute appetite. Longer-term effects and mechanisms require further work, but initial evidence implicates physical structure, energy density, fibre, potassium and polyphenol content, as explanations for some of the observed responses.
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Jugos de Frutas y Vegetales , Frutas , Humanos , Azúcares de la Dieta/administración & dosificación , Miel/análisis , Dieta/métodos , Presión Sanguínea/fisiología , Presión Sanguínea/efectos de los fármacos , Bebidas Azucaradas , Apetito/fisiología , Apetito/efectos de los fármacos , Inflamación , Control Glucémico/métodosRESUMEN
Glycomacropeptide (GMP) has a unique amino acid profile which may make less satiating than other dietary proteins. This study assessed the feasibility and likely acceptability of a leucine-enriched GMP drink and determined appetite response in older adults (OA). Thirteen OA (11f; 70 ± 4 years) were recruited for sensory assessments of a leucine-enriched GMP drink when mixed with water and with fruit smoothie, compared with whey protein isolate (WHEY). Participants also partook in a single focus group exploring acceptability to protein and supplementation. Separately, a counterbalanced, double-blind study with twelve OA (8f; 69 ± 3 years) was conducted to determine appetite and gut hormone responses. Fasting subjective appetite was recorded using visual analogue scales and a fasted venous blood sample was collected (to measures acyl-ghrelin, PYY, GLP-1, and CCK) before participants consumed either: GMP protein (27g + 3g leucine, 350 mL water), WHEY (30g, 350 mL water), or water. Participants rested for 240 min, with appetite measures and blood sampling throughout. An ad libitum pasta-based meal was then consumed. Sensory testing revealed low pleasantness rating for GMP in water vs. WHEY (16 ± 14 vs 31 ± 24, p = 0.016). GMP addition to smoothie reduced pleasantness (26 ± 21 vs. 61 ± 29, p = 0.009) and worsened the aroma (46 ± 15 vs. 69 ± 28, p = 0.014). The focus group revealed uncertainty of protein needs and a scepticism of supplements, with preference for food. Gut hormone response did not differ between GMP and WHEY (nAUC for all gut hormones p > 0.05). There was no difference between conditions for lunch ad libitum intake (549 ± 171 kcal, 512 ± 238 kcal, 460 ± 199 kcal for GMP, WHEY, and water, p = 0.175), or for subjective appetite response. Leucine-enriched GMP was not less satiating than WHEY, and low palatability and scepticism of supplements question the likely acceptability of GMP supplementation. Providing trusted nutritional advice and food enrichment/fortification may be preferred strategies for increasing protein intake in OA.
Asunto(s)
Apetito , Caseínas , Estudios de Factibilidad , Hormonas Gastrointestinales , Fragmentos de Péptidos , Proteína de Suero de Leche , Humanos , Femenino , Masculino , Apetito/efectos de los fármacos , Anciano , Proyectos Piloto , Hormonas Gastrointestinales/sangre , Método Doble Ciego , Caseínas/administración & dosificación , Caseínas/farmacología , Proteína de Suero de Leche/administración & dosificación , Proteína de Suero de Leche/farmacología , Fragmentos de Péptidos/sangre , Leucina/administración & dosificación , Leucina/farmacología , Ghrelina/sangre , Saciedad/efectos de los fármacos , Ingestión de Alimentos , Suplementos Dietéticos , Persona de Mediana Edad , Péptido YY/sangre , Péptido 1 Similar al Glucagón/sangre , Proteínas en la Dieta/administración & dosificaciónRESUMEN
Our previous research identified interleukin-4 (IL-4) as a key regulator of glucose/lipid metabolism, circulatory leptin levels, and insulin action, suggesting its potential as a therapeutic target for obesity and related complications. This study aimed to further elucidate the role of IL-4 in regulating hypothalamic appetite-controlling neuropeptides using leptin dysfunctional Leptin145E/145E mice as the experimental model. IL-4 significantly reduces body weight, food intake, and serum glucose levels. Our data demonstrated that IL-4 exhibits multiple functions in regulating hypothalamic appetite control, including downregulating orexigenic agouti-related peptide and neuropeptide Y levels, promoting expression of anorexigenic proopiomelanocortin, alleviating microenvironmental hypothalamic inflammation, enhancing leptin and insulin pathway, and attenuating insulin resistance. Furthermore, IL-4 promotes uncoupling protein 1 expression of white adipose tissue (WAT), suggesting its role in triggering WAT-beige switch. In summary, this study uncovers novel function of IL-4 in mediating food-intake behaviors and metabolic efficiency by regulating hypothalamic appetite-control and WAT browning activities. These findings support the therapeutic potential of targeting hypothalamic inflammation and reducing adiposity through IL-4 intervention for tackling the pandemic increasing prevalence of obesity and associated metabolic disorders.
Asunto(s)
Hipotálamo , Insulina , Interleucina-4 , Leptina , Transducción de Señal , Animales , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Interleucina-4/metabolismo , Ratones , Transducción de Señal/efectos de los fármacos , Leptina/metabolismo , Insulina/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Masculino , Quinasas Janus/metabolismo , Regulación del Apetito/efectos de los fármacos , Apetito/efectos de los fármacos , Factores de Transcripción STAT/metabolismo , Ingestión de Alimentos/efectos de los fármacos , Tejido Adiposo Blanco/efectos de los fármacos , Tejido Adiposo Blanco/metabolismoRESUMEN
Brewers spent grain (BSG) is a valuable source of arabinoxylans with potential beneficial effects on glucose values. This pilot randomised crossover double-blind trial compared the effects of panettone, a sweet baked-product, enriched with BSG-fibre (p-rich) to unenriched panettone (p-standard) on glucose and insulin blood values and appetite scores. Ten healthy volunteers consumed each food in a random order. Blood variables and appetite scores were assessed at fasting and at different intervals after each food consumption. Glucose values were significantly higher after p-standard intake at 90-min (89.9 ± 16.1 vs 74.6 ± 19.4 mg/dL) and 120-min (81.1 ± 9.85 vs 72.1 ± 14.0 mg/dL). The areas-under-the-curve (AUCs) were lower for both glucose (p = .043) and insulin values (p = .036) with p-rich. At 240-min, satiety was higher (p = .006), and desire-to-eat lower (p = .008) with p-rich; desire-to-eat AUC was lower with p-rich too (p = .029). The integration of a small amount of BSG-derived fibre into a sweet food led to improved glycaemic control and appetite regulation.
Asunto(s)
Apetito , Glucemia , Estudios Cruzados , Fibras de la Dieta , Insulina , Humanos , Fibras de la Dieta/farmacología , Insulina/sangre , Apetito/efectos de los fármacos , Masculino , Adulto , Proyectos Piloto , Femenino , Método Doble Ciego , Alimentos Fortificados , Adulto Joven , Pan/análisis , Grano Comestible/química , Periodo Posprandial , Saciedad/efectos de los fármacos , Persona de Mediana EdadRESUMEN
We studied the effect of separate and combined influence of chronic forced physical activity reduction and high-fat and high-carbohydrate diet containing cholesterol on some indicators of carbohydrate, lipid, and cholesterol metabolism in growing male Wistar rats. Used combination of factors simulating a sedentary lifestyle and unhealthy diet did not have a synergistic effect on the selected biomarkers. On the contrary, the effect was antagonistic: body weight and appetite decreased and insulin resistance increased. The obtained results indicate certain prospects of hypercholesterolemia model using in preclinical studies of specialized food products to optimize the diet of individuals with disorders of carbohydrate and lipid metabolism.
Asunto(s)
Colesterol , Dieta Alta en Grasa , Metabolismo de los Lípidos , Ratas Wistar , Animales , Masculino , Ratas , Dieta Alta en Grasa/efectos adversos , Metabolismo de los Lípidos/efectos de los fármacos , Colesterol/metabolismo , Colesterol/sangre , Resistencia a la Insulina , Peso Corporal/efectos de los fármacos , Carbohidratos de la Dieta/administración & dosificación , Carbohidratos de la Dieta/farmacología , Hipercolesterolemia/metabolismo , Hipercolesterolemia/dietoterapia , Inmovilización , Colesterol en la Dieta/administración & dosificación , Apetito/efectos de los fármacos , Apetito/fisiología , Condicionamiento Físico Animal/fisiologíaRESUMEN
PURPOSE: Secretin activates brown adipose tissue (BAT) and induces satiation in both mice and humans. However, the exact brain mechanism of this satiety inducing, secretin-mediated gut-BAT-brain axis is largely unknown. METHODS AND RESULTS: In this placebo-controlled, single-blinded neuroimaging study, firstly using [18F]-fluorodeoxyglucose (FDG) PET measures (n = 15), we established that secretin modulated brain glucose consumption through the BAT-brain axis. Predominantly, we found that BAT and caudate glucose uptake levels were negatively correlated (r = -0.54, p = 0.037) during secretin but not placebo condition. Then, using functional magnetic resonance imaging (fMRI; n = 14), we found that secretin improved inhibitory control and downregulated the brain response to appetizing food images. Finally, in a PET-fMRI fusion analysis (n = 10), we disclosed the patterned correspondence between caudate glucose uptake and neuroactivity to reward and inhibition, showing that the secretin-induced neurometabolic coupling patterns promoted satiation. CONCLUSION: These findings suggest that secretin may modulate the BAT-brain metabolic crosstalk and subsequently the neurometabolic coupling to induce satiation. The study advances our understanding of the secretin signaling in motivated eating behavior and highlights the potential role of secretin in treating eating disorders and obesity. TRIAL REGISTRATION: EudraCT no. 2016-002373-35, registered 2 June 2016; Clinical Trials no. NCT03290846, registered 25 September 2017.
Asunto(s)
Tejido Adiposo Pardo , Apetito , Eje Cerebro-Intestino , Encéfalo , Conducta Alimentaria , Neuroimagen Funcional , Respuesta de Saciedad , Secretina , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Pardo/fisiología , Apetito/efectos de los fármacos , Apetito/fisiología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/fisiología , Secretina/metabolismo , Secretina/farmacología , Respuesta de Saciedad/efectos de los fármacos , Respuesta de Saciedad/fisiología , Eje Cerebro-Intestino/efectos de los fármacos , Eje Cerebro-Intestino/fisiología , Método Simple Ciego , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Glucosa/metabolismo , Recompensa , Transducción de Señal/efectos de los fármacos , Humanos , Conducta Alimentaria/efectos de los fármacos , AlimentosRESUMEN
Obesity is a serious global health problem because of its increasing prevalence and comorbidities, but its treatments are limited. The serotonin 2C receptor (5-HT2CR), a G-protein-coupled receptor, activates proopiomelanocortin (POMC) neurons in the arcuate nucleus of hypothalamus (ARH) to reduce appetite and weight gain. However, several 5-HT analogs targeting this receptor, e.g., lorcaserin (Lor), suffer from diminished efficacy to reduce weight after prolonged administration. Here, we show that barbadin (Bar), a novel ß-arrestin/ß2-adaptin inhibitor, can prevent 5-HT2CR internalization in cells and potentiate long-term effects of Lor to reduce appetite and body weight in male mice. Mechanistically, we demonstrate that Bar co-treatment can effectively maintain the sensitivity of the 5-HT2CR in POMCARH neurons, despite prolonged Lor exposure, thereby allowing these neurons to be activated through opening the transient receptor potential cation (TRPC) channels. Thus, our results prove the concept that inhibition of 5-HT2CR desensitization can be a valid strategy to improve the long-term weight loss effects of Lor or other 5-HT2CR agonists, and also provide an intellectual framework to develop effective long-term management of weight by targeting 5-HT2CR desensitization.SIGNIFICANCE STATEMENT By demonstrating that the combination of barbadin (Bar) with a G-protein-coupled receptor (GPCR) agonist can provide prolonged weight-lowering benefits in a preclinical setting, our work should call for additional efforts to validate Bar as a safe and effective medicine or to use Bar as a lead compound to develop more suitable compounds for obesity treatment. These results prove the concept that inhibition of serotonin 2C receptor (5-HT2CR) desensitization can be a valid strategy to improve the long-term weight loss effects of lorcaserin (Lor) or other 5-HT2CR agonists. Since GPCRs represent a major category as therapeutic targets for various human diseases and desensitization of GPCRs is a common issue, our work may provide a conceptual framework to enhance effects of a broad range of GPCR medicines.
Asunto(s)
Benzazepinas/farmacología , Neuronas/efectos de los fármacos , Pirimidinas/farmacología , Receptor de Serotonina 5-HT2C/metabolismo , Pérdida de Peso/efectos de los fármacos , Animales , Apetito/efectos de los fármacos , Núcleo Arqueado del Hipotálamo/efectos de los fármacos , Núcleo Arqueado del Hipotálamo/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Proopiomelanocortina/metabolismo , Receptor de Serotonina 5-HT2C/efectos de los fármacos , TiempoRESUMEN
BACKGROUND/OBJECTIVES: Evidence regarding the influence of coffee on appetite and weight control is equivocal and the influence of covariates, such as genetic variation in caffeine metabolism, remains unknown. Herein, we addressed the novel hypothesis that genetic variation in CYP1A2, a gene responsible for more than 95% of caffeine metabolism, differentially impacts the association of coffee consumption with appetite and BMI among individuals with different genetic predispositions to obesity. SUBJECTS/METHODS: A cross-over randomized intervention study involving 18 volunteers assessed the effects of coffee consumption on dietary intake, appetite, and levels of the appetite-controlling hormones asprosin and leptin. Data on habitual coffee intake, BMI, and perceived appetite were obtained from an observational cohort of 284 volunteers using validated questionnaires. Participants were stratified according to a validated genetic risk score (GRS) for obesity and to the -163C > A (rs762551) polymorphism of CYP1A2 as rapid (AA), intermediate (AC), or slow (CC) caffeine metabolizers. RESULTS: Coffee consumption led to lower energy and dietary fat intake and circulating asprosin levels (P for interaction of rs762551 genotype*coffee consumption=0.056, 0.039, and 0.043, respectively) as compared to slow/intermediate metabolizers. High coffee consumption was more prevalent in rapid compared to slow metabolizers (P = 0.008 after adjustment for age, sex, and BMI) and was associated with lower appetite perception and lower BMI only in rapid metabolizers (P for interaction of rs762551 genotype*coffee consumption = 0.002 and 0.048, respectively). This differential association of rs762551 genotype and coffee consumption with BMI was more evident in individuals at higher genetic risk of obesity (mean adjusted difference in BMI = -5.82 kg/m2 for rapid versus slow/intermediate metabolizers who consumed more than 14 cups of coffee per week). CONCLUSIONS: CYP1A2 rs762551 polymorphism modifies the association of habitual coffee consumption with BMI, in part by influencing appetite, energy intake and circulating levels of the orexigenic hormone asprosin. This association is more evident in subjects with high genetic predisposition to obesity. ClinicalTrials.gov: registered Clinical Trial NCT04514588.
Asunto(s)
Apetito/efectos de los fármacos , Café/metabolismo , Citocromo P-450 CYP1A2/farmacología , Ingestión de Alimentos/efectos de los fármacos , Adolescente , Apetito/fisiología , Índice de Masa Corporal , Café/efectos de los fármacos , Estudios de Cohortes , Estudios Cruzados , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP1A2/metabolismo , Ingestión de Alimentos/fisiología , Conducta Alimentaria/fisiología , Femenino , Voluntarios Sanos/estadística & datos numéricos , Humanos , Masculino , Polimorfismo de Nucleótido Simple/genética , Adulto JovenRESUMEN
OBJECTIVE: To identify predictors of changes in height, weight, and body mass index (BMI) in children with attention deficit hyperactivity disorder (ADHD) starting central nervous system (CNS) stimulants. STUDY DESIGN: There were 230 medication-naïve children aged 5-12 years with ADHD who participated in a randomized trial evaluating the impact of CNS stimulants on growth over 30 months. This observational analysis focused on the 141 participants using study medication for 65 or more days in the first 6-months after starting medication. Biometric variables, ADHD, and oppositional defiant disorder symptom scores at medication initiation, and medication use over the study were examined as predictors of changes in standardized (z) height, weight, and BMI. RESULTS: Mean changes in z-BMI, z-weight. and z-height were negative throughout the study. The most consistent predictors of change in z-BMI, z-weight, and z-height were percent days medicated and total medication exposure. Children with lower z-height and z-weight at medication initiation experienced greater z-BMI and z-weight decreases over the first 6 months on medication. Greater appetite suppression during dose optimization predicted greater decreases in z-weight over the entire study and a greater decrease in z-height over the first 6 months on medication. z-weight change correlated with z-height change. Behavioral symptoms did not predict changes in z-BMI, z-weight, or z-height. CONCLUSIONS: How much and how often CNS stimulants are used predicts changes in z-BMI, z-weight, and z-height in children. Even smaller and lighter children may be at risk for decreases in z-weight and z-BMI. Parent ratings of appetite during dose titration may serve as feasible indicators of future weight and height change in children using CNS stimulants. TRIAL REGISTRATION: Clinicialtrials.gov: NCT01109849.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estatura/efectos de los fármacos , Índice de Masa Corporal , Peso Corporal/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/uso terapéutico , Adolescente , Apetito/efectos de los fármacos , Niño , Preescolar , Femenino , Humanos , MasculinoRESUMEN
Eating chocolate in the morning or in the evening/at night, may differentially affect energy balance and impact body weight due to changes in energy intake, substrate oxidation, microbiota (composition/function), and circadian-related variables. In a randomized controlled trial, postmenopausal females (n = 19) had 100 g of chocolate in the morning (MC), in the evening/at night (EC), or no chocolate (N) for 2 weeks and ate any other food ad libitum. Our results show that 14 days of chocolate intake did not increase body weight. Chocolate consumption decreased hunger and desire for sweets (P < .005), and reduced ad libitum energy intake by ~300 kcal/day during MC and ~150 kcal/day during EC (P = .01), but did not fully compensate for the extra energy contribution of chocolate (542 kcal/day). EC increased physical activity by +6.9%, heat dissipation after meals +1.3%, and carbohydrate oxidation by +35.3% (P < .05). MC reduced fasting glucose (4.4%) and waist circumference (-1.7%) and increased lipid oxidation (+25.6%). Principal component analyses showed that both timings of chocolate intake resulted in differential microbiota profiles and function (P < .05). Heat map of wrist temperature and sleep records showed that EC induced more regular timing of sleep episodes with lower variability of sleep onset among days than MC (60 min vs 78 min; P = .028). In conclusion, having chocolate in the morning or in the evening/night results in differential effects on hunger and appetite, substrate oxidation, fasting glucose, microbiota (composition and function), and sleep and temperature rhythms. Results highlight that the "when" we eat is a relevant factor to consider in energy balance and metabolism.
Asunto(s)
Apetito/efectos de los fármacos , Índice de Masa Corporal , Carbohidratos/química , Chocolate/efectos adversos , Hambre/efectos de los fármacos , Microbiota/efectos de los fármacos , Anciano , Glucemia/análisis , Estudios Cruzados , Ingestión de Energía , Ayuno , Femenino , Humanos , Persona de Mediana Edad , Periodo Posprandial , Factores de TiempoRESUMEN
Mammalian taste buds are comprised of specialized neuroepithelial cells that act as sensors for molecules that provide nutrition (e.g., carbohydrates, amino acids, and salts) and those that are potentially harmful (e.g., certain plant compounds and strong acids). Type II and III taste bud cells (TBCs) detect molecules described by humans as "sweet," "bitter," "umami," and "sour." TBCs that detect metallic ions, described by humans as "salty," are undefined. Historically, type I glial-like TBCs have been thought to play a supportive role in the taste bud, but little research has been done to explore their role in taste transduction. Some evidence implies that type I cells may detect sodium (Na+) via an amiloride-sensitive mechanism, suggesting they play a role in Na+ taste transduction. We used an optogenetic approach to study type I TBCs by driving the expression of the light-sensitive channelrhodopsin-2 (ChR2) in type I GAD65+ TBCs of male and female mice. Optogenetic stimulation of GAD65+ TBCs increased chorda tympani nerve activity and activated gustatory neurons in the rostral nucleus tractus solitarius. "N neurons," whose NaCl responses were blocked by the amiloride analog benzamil, responded robustly to light stimulation of GAD65+ TBCs on the anterior tongue. Two-bottle preference tests were conducted under Na+-replete and Na+-deplete conditions to assess the behavioral impact of optogenetic stimulation of GAD65+ TBCs. Under Na+-deplete conditions GAD65-ChR2-EYFP mice displayed a robust preference for H2O illuminated with 470 nm light versus nonilluminated H2O, suggesting that type I glial-like TBCs are sufficient for driving a behavior that resembles Na+ appetite.SIGNIFICANCE STATEMENT This is the first investigation on the role of type I GAD65+ taste bud cells (TBCs) in taste-mediated physiology and behavior via optogenetics. It details the first definitive evidence that selective optogenetic stimulation of glial-like GAD65+ TBCs evokes neural activity and modulates behavior. Optogenetic stimulation of GAD65+ TBCs on the anterior tongue had the strongest effect on gustatory neurons that responded best to NaCl stimulation through a benzamil-sensitive mechanism. Na+-depleted mice showed robust preferences to "light taste" (H2O illuminated with 470 nm light vs nonilluminated H2O), suggesting that the activation of GAD65+ cells may generate a salt-taste sensation in the brain. Together, our results shed new light on the role of GAD65+ TBCs in gustatory transduction and taste-mediated behavior.
Asunto(s)
Apetito/fisiología , Preferencias Alimentarias/fisiología , Glutamato Descarboxilasa/fisiología , Optogenética/métodos , Células Receptoras Sensoriales/fisiología , Sodio/deficiencia , Papilas Gustativas/fisiología , Amilorida/farmacología , Animales , Apetito/efectos de los fármacos , Channelrhodopsins , Nervios Craneales/fisiología , Diuréticos/farmacología , Femenino , Preferencias Alimentarias/efectos de los fármacos , Glutamato Descarboxilasa/efectos de los fármacos , Masculino , Ratones , Células Receptoras Sensoriales/efectos de los fármacos , Cloruro de Sodio/farmacología , Papilas Gustativas/efectos de los fármacosRESUMEN
Previous studies using male rodents showed the adipocyte-derived hormone leptin acts in the brain to regulate cardiovascular function, energy balance, and glucose homeostasis. The importance of sex differences in cardiometabolic responses to leptin, however, is still unclear. We examined potential sex differences in leptin's chronic central nervous system (CNS)-mediated actions on blood pressure (BP), heart rate (HR), appetite, and glucose homeostasis in normal and type 1 diabetic rats. Female and male Sprague-Dawley (SD) rats were instrumented with intracerebroventricular cannulas for continuous 7-day leptin infusion (15 µg/day), and BP and HR were measured by telemetry 24 h/day. At baseline, females had lower mean arterial pressure (MAP) (96 ± 3 vs. 104 ± 4 mmHg, P < 0.05) but higher HR (375 ± 5 vs. 335 ± 5 beats/min, P < 0.05) compared with males. After leptin treatment, we observed similar increases in BP (â¼3 mmHg) and HR (â¼25 beats/min) in both sexes. Females had significantly lower body weight (BW, 283 ± 2 vs. 417 ± 7 g, P < 0.05) and caloric intake (162 ± 20 vs. 192 ± 9 kcal/kg of body wt, P < 0.05) compared with males, and leptin infusion reduced BW (-10%) and caloric intake (-62%) similarly in both sexes. In rats with streptozotocin-induced diabetes (n = 5/sex), intracerebroventricular leptin treatment for 7 days completely normalized glucose levels. The same dose of leptin administered intraperitoneally did not alter MAP, HR, glucose levels, or caloric intake in normal or diabetic rats. These results show that leptin's CNS effects on BP, HR, glucose regulation, and energy homeostasis are similar in male and female rats. Therefore, our results provide no evidence for sex differences in leptin's brain-mediated cardiovascular or metabolic actions.
Asunto(s)
Apetito/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Glucosa/metabolismo , Frecuencia Cardíaca/efectos de los fármacos , Homeostasis/efectos de los fármacos , Leptina/farmacología , Animales , Diabetes Mellitus Experimental , Femenino , Inyecciones Intraventriculares , Leptina/administración & dosificación , Masculino , Ratas , Ratas Sprague-Dawley , Factores SexualesRESUMEN
BACKGROUND: A low-protein diet can induce compensatory intake of excess energy. This must be better evaluated to anticipate the obesogenic risk that may result from the dietary recommendations for reducing animal protein consumption. OBJECTIVES: We aimed to further characterize the behavioral and physiological responses to a reduction in dietary protein and to identify the determinants of protein appetite. METHODS: Thirty-two male Wistar rats [4 wk old, (mean ± SEM) 135 ± 32 g body weight] were fed a low-protein (LP; 6% energy value) or normal-protein (NP; 20%) diet for 8 wk. Food intake and body mass were measured during the entire intervention. During self-selection sessions after 4 wk of experimental diets, we evaluated rat food preference between LP, NP, or high-protein (HP; 55%) pellets. At the end of the experiment, we assessed their hedonic response [ultrasonic vocalizations (USVs)] and c-Fos neuronal activation in the olfactory tubercle and nucleus accumbens (NAcc) associated with an LP or HP meal. RESULTS: Rats fed an LP diet had greater food intake (24%), body weight (5%), and visceral adiposity (30%) than NP rats. All LP rats and half of the NP rats showed a nearly exclusive preference for HP pellets during self-selection sessions, whereas the other half of the NP rats showed no preference. This suggests that the appetite for proteins is driven not only by a low protein status but also by individual traits in NP rats. LP or HP meal induced similar USV emission and similar neuronal activation in the NAcc in feed-deprived LP and NP rats, showing no specific response linked to protein appetite. CONCLUSIONS: Protein appetite in rats is driven by low protein status or individual preferences in rats receiving adequate protein amounts. This must be considered and further analyzed, in the context of current recommendations for protein intake reduction.
Asunto(s)
Apetito/efectos de los fármacos , Dieta con Restricción de Proteínas , Proteínas en la Dieta/farmacología , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Energía/efectos de los fármacos , Preferencias Alimentarias/efectos de los fármacos , Fenotipo , Adiposidad , Animales , Peso Corporal , Proteínas en la Dieta/administración & dosificación , Grasa Intraabdominal , Masculino , Carne , Núcleo Accumbens , Obesidad , Tubérculo Olfatorio , Ratas WistarRESUMEN
The purpose of the present study was to compare next-morning responses of RMR and appetite to pre-sleep consumption of casein protein (CP) in pre- and postmenopausal women. The study was a randomised, crossover, double-blind, placebo-controlled trial. Seven sedentary premenopausal (age: 19·9 (sd 1·2) years; BMI: 23·1 (sd 2·6) kg/m2) and seven sedentary postmenopausal (age: 56·4 (sd 4·9) years; BMI: 26·3 (sd 3·5) kg/m2) women participated. During visit one, anthropometrics and body composition were measured. Following visit one, subjects consumed either CP (25 g) or placebo (PL) ≥2 h after their last meal and ≤30 min prior to sleep on the night before visits two and three. Visits two and three occurred ≥1 week after visit one and were 48 h apart. During visits two and three, RMR (VO2), RER and appetite were measured via indirect calorimetry and visual analogue scale, respectively. Anthropometrics and body composition were analysed by one-way ANOVA. RMR and measures of appetite were analysed using a 2 × 2 (menopause status × CP/PL) repeated-measures ANOVA. Significance was accepted at P ≤ 0·05. RMR was significantly lower in postmenopausal compared with premenopausal women under both conditions (P = 0·003). When consumed pre-sleep CP did not alter RMR, RER or appetite compared with PL when assessed next morning in pre- and postmenopausal women. These data contribute to growing evidence that pre-sleep consumption of protein is not harmful to next-morning metabolism or appetite. In addition, these data demonstrate that menopause may not alter next-morning RMR, RER or appetite after pre-sleep consumption of CP.
Asunto(s)
Apetito/efectos de los fármacos , Metabolismo Basal/efectos de los fármacos , Caseínas/administración & dosificación , Posmenopausia/metabolismo , Premenopausia/metabolismo , Adolescente , Antropometría , Composición Corporal , Índice de Masa Corporal , Calorimetría Indirecta , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Persona de Mediana Edad , Conducta Sedentaria , Sueño , Factores de TiempoRESUMEN
Stimulation of gastrointestinal taste receptors affects eating behaviour. Intraduodenal infusion of tastants leads to increased satiation and reduced food intake, whereas intraileal infusion of tastants does not affect eating behaviour. Currently, it is unknown whether oral- or intragastric administration of tastants induces a larger effect on eating behaviour. This study investigated the effects of oral- and/or intragastric administration of quinine on food intake, appetite sensations and heart rate variability (HRV). In a blinded randomised crossover trial, thirty-two healthy volunteers participated in four interventions with a 1-week washout: oral placebo and intragastric placebo (OPGP), oral quinine and intragastric placebo (OQGP), oral placebo and intragastric quinine (OPGQ) and oral quinine and intragastric quinine (OQGQ). On test days, 150 min after a standardised breakfast, subjects ingested a capsule containing quinine or placebo and were sham-fed a mixture of quinine or placebo orally. At 50 min after intervention, subjects received an ad libitum meal to measure food intake. Visual analogue scales for appetite sensations were collected, and HRV measurements were performed at regular intervals. Oral and/or intragastric delivery of the bitter tastant quinine did not affect food intake (OPGP: 3273·6 (sem 131·8) kJ, OQGP: 3072·7 (sem 132·2) kJ, OPGQ: 3289·0 (sem 132·6) kJ and OQGQ: 3204·1 (sem 133·1) kJ, P = 0·069). Desire to eat and hunger decreased after OQGP and OPGQ compared with OPGP (P < 0·001 and P < 0·05, respectively), whereas satiation, fullness and HRV did not differ between interventions. In conclusion, sole oral sham feeding with and sole intragastric delivery of quinine decreased desire to eat and hunger, without affecting food intake, satiation, fullness or HRV.