RESUMEN
The inositol pyrophosphate IP7 (5-diphosphoinositolpentakisphosphate), formed by a family of three inositol hexakisphosphate kinases (IP6Ks), modulates diverse cellular activities. We now report that IP7 is a physiologic inhibitor of Akt, a serine/threonine kinase that regulates glucose homeostasis and protein translation, respectively, via the GSK3ß and mTOR pathways. Thus, Akt and mTOR signaling are dramatically augmented and GSK3ß signaling reduced in skeletal muscle, white adipose tissue, and liver of mice with targeted deletion of IP6K1. IP7 affects this pathway by potently inhibiting the PDK1 phosphorylation of Akt, preventing its activation and thereby affecting insulin signaling. IP6K1 knockout mice manifest insulin sensitivity and are resistant to obesity elicited by high-fat diet or aging. Inhibition of IP6K1 may afford a therapeutic approach to obesity and diabetes.
Asunto(s)
Fosfatos de Inositol/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Aumento de Peso , Adipogénesis , Envejecimiento/metabolismo , Animales , Técnicas de Cultivo de Célula , Dieta , Difosfatos/metabolismo , Inositol/metabolismo , Insulina/metabolismo , Resistencia a la Insulina , Ratones , Obesidad/metabolismo , Fosforilación , Fosfotransferasas (Aceptor del Grupo Fosfato)/genéticaRESUMEN
Nutritional status has clinical relevance and is a target of guidance to parents of children with cystic fibrosis (CF). Growth is routinely monitored in CF clinics but there is no standardized way of assessing appetitive behaviors or parents' perceptions of their children's appetite. Greater understanding of these factors could improve clinical guidance regarding parent feeding behaviors. We therefore aimed to assess parent perceptions of child weight, and parent reports of child appetite using the Baby Eating Behavior Questionnaire (BEBQ), in a sample of infants and toddlers with CF, compared with a community sample. We additionally assessed relationships of parent perceptions of child weight with parent feeding behaviors in the sample with CF. Anthropometric and questionnaire data were collected for 32 infants and toddlers with CF, as well as 193 infants and toddlers drawn from RESONANCE, a community cohort study. Parents perceived children with CF to be lower in weight than their actual weight, to a greater extent than was evident in the community sample. Parents who perceived their children with CF to be underweight vs. right weight reported greater slowness in eating on the BEBQ. Parents perceived children with CF to have greater slowness in eating and lower enjoyment of food, compared to parents of children in the community sample, independent of sample differences in child weight, age, and sex. Our results demonstrate the potential utility of the BEBQ in a clinical sample and suggest it may be helpful for clinicians to assess parents' perceptions of their child's weight and appetite to promote a fuller understanding of the child's nutritional status, facilitate appropriate feeding behaviors and alleviate unnecessary concerns.
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Apetito , Peso Corporal , Fibrosis Quística , Conducta Alimentaria , Padres , Humanos , Fibrosis Quística/psicología , Masculino , Femenino , Lactante , Padres/psicología , Conducta Alimentaria/psicología , Encuestas y Cuestionarios , Preescolar , Estado Nutricional , Percepción , Delgadez/psicología , Estudios de CohortesRESUMEN
Expression of synphilin-1 in neurons induces hyperphagia and obesity in a Drosophila model. However, the molecular pathways underlying synphilin-1-linked obesity remain unclear. Here, Drosophila models and genetic tools were used to study the synphilin-1-linked pathways in energy balance by combining molecular biology and pharmacological approaches. We found that expression of human synphilin-1 in flies increased AMP-activated kinase (AMPK) phosphorylation at Thr172 compared with that in non-transgenic flies. Knockdown of AMPK reduced AMPK phosphorylation and food intake in non-transgenic flies, and further suppressed synphilin-1-induced AMPK phosphorylation, hyperphagia, fat storage and body weight gain in transgenic flies. Expression of constitutively activated AMPK significantly increased food intake and body weight gain in non-transgenic flies, but it did not alter food intake in the synphilin-1 transgenic flies. In contrast, expression of dominant-negative AMPK reduced food intake in both non-transgenic and synphilin-1 transgenic flies. Treatment with STO-609 also suppressed synphilin-1-induced AMPK phosphorylation, hyperphagia and body weight gain. These results demonstrate that the AMPK signaling pathway plays a critical role in synphilin-1-induced hyperphagia and obesity. These findings provide new insights into the mechanisms of synphilin-1-controlled energy homeostasis.
Asunto(s)
Proteínas Quinasas Activadas por AMP , Proteínas Portadoras/genética , Drosophila , Hiperfagia , Proteínas del Tejido Nervioso/genética , Obesidad , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Animales Modificados Genéticamente , Drosophila/genética , Drosophila/metabolismo , Humanos , Hiperfagia/genética , Obesidad/genética , Transducción de Señal/genéticaRESUMEN
BACKGROUND: Previously, we reported short-term improvements in auditory attention, oromotor processing speed, and executive function during the active weight loss phase following bariatric surgery that persisted out to 3 months. In this study, our aims were to investigate the relationship between weight loss and cognitive performance in these patients 1 year following vertical sleeve gastrectomy (VSG) and Roux-en Y gastric bypass (RYGB) surgery and to determine whether preoperative cognitive performance predicted weight loss. METHODS: Adult women ages 18-55 approved for bariatric surgery completed a cognitive battery prior to and at 2, 12, 24, and 52 weeks following VSG (N = 17) or RYGB (N = 18). Scores from each task were assigned to one of the following cognitive domains: auditory attention, processing speed, memory, and executive functioning. Weight loss and cognitive scores for each domain were calculated and compared between cohorts. RESULTS: RYGB surgery resulted in greater weight loss at 1-year follow-up relative to VSG. Both VSG and RYGB procedures resulted in improved performance on different measures of auditory attention and both surgery groups improved across all processing speed tasks. Within the executive function domain, both groups showed improvements, but only the RYGB procedure resulted in improved performance in the Trail Making Test. Baseline auditory attention and memory performance predicted weight loss at 1 year following RYGB but not VSG surgery. Controlling for baseline cognitive performance, percent total weight loss predicted auditory attention at 1 year following RYGB but not VSG surgery. CONCLUSIONS: Bariatric surgery type may result in selective improvements in cognition during the first year following surgery. Presurgical cognitive performance as well as surgery type appears to influence weight loss outcomes.
Asunto(s)
Cirugía Bariátrica , Derivación Gástrica , Obesidad Mórbida , Adulto , Humanos , Femenino , Adolescente , Adulto Joven , Persona de Mediana Edad , Pérdida de Peso , Derivación Gástrica/métodos , Gastrectomía/métodos , Cognición , Obesidad Mórbida/cirugía , Obesidad Mórbida/psicologíaRESUMEN
BACKGROUND: Alterations in gut hormone secretion and reported changes in taste preferences have been suggested to contribute to the weight-reducing effects of bariatric surgery. However, a link between changes in gut hormone secretion and taste preferences following bariatric surgery has yet to be elucidated. METHODS: Here we examined the potential relationships between gut hormone responses (GLP-1 and PYY3-36 peak, ghrelin trough) to a test meal of Ensure and liking ratings for taste mixtures varying in sugar and fat content before and following bariatric surgery (vertical sleeve gastrectomy (VSG): N = 4; Roux-en Y gastric bypass (RYGB): N = 8). RESULTS: Significant increases in GLP-1 and PYY3-36 peak and a significant drop in ghrelin trough were observed following surgery. Pre- and postoperation, patients with higher postprandial GLP-1 or PYY3-36 peaks gave lower liking ratings for mixtures containing a combination of fat and sugar (half and half + 20% added sugar) whereas, for the combined surgery analyses, no relationships were found with solutions comprised of high fat (half and half + 0% sugar), predominantly high sugar (skim milk + 20% added sugar), or low fat and low sugar (skim milk + 0% added sugar). Within the RYGB patients, patients with the greatest increase in postprandial GLP-1 peak from preoperation to postoperation also demonstrated the greatest decrease in liking for half & half + 20% added sugar and skim milk + 20% added sugar, but not the unsweetened version of each solution. No pre- or postoperative relationship between ghrelin and liking ratings were observed. CONCLUSION: Gut hormone responses following bariatric surgery may contribute to taste processing of sugar+fat mixtures and together influence weight loss.
Asunto(s)
Cirugía Bariátrica , Derivación Gástrica , Obesidad Mórbida , Humanos , Ghrelina , Proyectos Piloto , Gusto , Gastrectomía , Pérdida de Peso , Péptido 1 Similar al Glucagón , Azúcares , Obesidad Mórbida/cirugíaRESUMEN
Administration of cholecystokinin (CCK) or the glucagon-like peptide 1 (GLP-1) receptor agonist Exendin-4 (Ex-4) reduces food intake. Findings in the literature suggest CCK reduces intake primarily as a satiety signal whereas GLP-1 may play a role in both satiety and reward-related feeding signals. Compounds that humans describe as âsweetâ and âfattyâ are palatable yet are signaled via separate transduction pathways. Here, unconditioned lick responses to sucrose and intralipid were measured in a brief-access lick procedure in food-restricted male rats in response to i.p. administration of Ex-4 (3 h before test), CCK (30 min before test), or a combination of both. The current experimental design measures lick responses to water and varying concentrations of both sucrose (0.03, 0.1, and 0.5 M) and intralipid (0.2%, 2%, and 20%) during 10-s trials across a 30-min single test session. This design minimized postingestive influences. Compared with saline-injected controls, CCK (1.0, 3.0, or 6.0 µg/kg) did not change lick responses to sucrose or intralipid. Number of trials initiated and lick responses to both sucrose and intralipid were reduced in rats injected with 3.0 µg/kg, but not 1.0 µg/kg Ex-4. The supplement of CCK did not alter lick responses or trials initiated compared with Ex-4 administration alone. These findings support a role for GLP-1 but not CCK in the oral responsiveness to palatable stimuli. Furthermore, Ex-4-induced reductions were observed for both sucrose and intralipid, compounds representing âsweetâ and âfat,â respectively.
Asunto(s)
Colecistoquinina , Sacarosa , Animales , Colecistoquinina/farmacología , Ingestión de Alimentos , Emulsiones , Exenatida/farmacología , Péptido 1 Similar al Glucagón/farmacología , Masculino , Fosfolípidos , Ratas , Aceite de Soja , Sacarosa/farmacologíaRESUMEN
OBJECTIVE: As patients with anorexia nervosa tend to "like" palatable tastants less than controls, we set out to model this preclinically by using the taste reactivity test (TRT) to assess hedonic state in rats following weight restoration from a bout of activity-based anorexia (ABA). METHOD: Female rats (n = 31) were surgically implanted with an intraoral catheter, which allowed experimenters to assess baseline TRT to six tastants. Following baseline TRT, animals were either exposed to the activity-based anorexia condition (ABA; 1.5HR chow/ad lib wheel until 25% weight loss), kept sedentary (SED; ad lib chow/locked wheel), given access to running wheels with ad lib chow access (RW; ad lib chow/wheel), or were body weight matched to the ABA group (BWM; restricted chow/locked wheel). Following 25% weight loss, wheels were locked and food returned to ABA rats. Paired RW groups had their wheels locked and paired BWM rats were given ad lib access to food. Animals were given 10 days to recover prior to a second TRT. Videos were analyzed for liking (tongue protrusions) and disliking (gape) behaviors. RESULTS: The ABA group displayed a significant within-subject reduction in cumulative lick responses to water and 1 M sucrose. Additionally, we found the SED and ABA group displayed a significant within-subject reduction in cumulative lick responses to .1 M sucrose. Positive hedonic responses did not decline in either the BWM or the RW groups. DISCUSSION: The data show a novel phenomenon that a history of ABA results in an anhedonia phenotype that mirrors aspects of AN. SIGNIFICANCE STATEMENT: Patients recovered from anorexia nervosa report anhedonia, or the lack of pleasure in consuming palatable foods. Unfortunately, the biological mechanism underpinning anhedonia in anorexia nervosa is not well understood. The current study assessed hedonic state in adolescent female rats prior to and 10 days recovered following the activity-based anorexia paradigm. Age-matched, running wheel-matched and body weight-matched control groups were also tested at the same time points.
Asunto(s)
Anorexia Nerviosa , Anorexia , Anhedonia , Animales , Anorexia/etiología , Modelos Animales de Enfermedad , Ingestión de Alimentos/fisiología , Femenino , Humanos , Actividad Motora/fisiología , Ratas , Sacarosa , Pérdida de PesoRESUMEN
OBJECTIVE: Anhedonia, which in part involves the lack of pleasure in consuming palatable food, is a long-lasting symptom observed in patients both when acutely ill and when long term recovered from Anorexia Nervosa. The neurocircuitry underlying this phenomenon is not well understood. Here we use the preclinical activity-based anorexia (ABA) model in adolescent female rats to assess the impact of excessive exercise, limited food intake and acute weight loss, on adolescent female rat orofacial responding to intraoral sucrose, as measured by the taste reactivity test (TRT). Animals were identified as either prone or resistant to this paradigm based on a weight loss criterion. Measures of food intake, running wheel activity, taste reactivity and medial prefrontal cortex astrocyte expression were compared across groups. METHODS: Adolescent female rats implanted with an intraoral catheter were given a TRT using 1 M (M) sucrose at baseline, max weight loss (25% weight loss from start of ABA or 7 full days on the paradigm) or 10 days recovered from the ABA paradigm. Animals were sacrificed after the final TRT and astrocyte density was measured via immunohistochemistry. RESULTS: Animals resistant to the ABA paradigm ran less than prone animals during the ABA period. Additionally, we found that resistant animals displayed more cumulative 'liking' responses to sucrose compared to prone animals at maximum weight loss. Finally, we found prone animals 10-days recovered from ABA had reduced medial prefrontal cortex astrocyte density compared to levels in resistant animals. DISCUSSION: Rats presented with the physiological challenge of the ABA paradigm either adapt their behavior to stabilize their body weight (i.e. resistant), or rapidly lose weight (i.e. prone). Furthermore, we found that prone animals have reduced orofacial responding to 1 M sucrose at maximum weight loss compared to responses in resistant animals, and this anhedonia-like behavior may be a result of reduced astrocyte density that affects cortical function.
Asunto(s)
Anorexia Nerviosa , Anorexia , Animales , Astrocitos , Modelos Animales de Enfermedad , Femenino , Humanos , Ratas , Pérdida de PesoRESUMEN
The antidepressant medication fluoxetine (FLX) is frequently prescribed for the management of mood-related illnesses in the adolescent population-yet its long-term neurobehavioral consequences are not understood. To investigate how juvenile FLX exposure influences feeding behavior in adulthood, we conducted two experiments. In Experiment 1, adolescent male and female Sprague-Dawley rats were administered with 20 mg/kg/day FLX (postnatal day [PND] 35-49) and exposed to a binge access paradigm in adulthood (PND72+) to evaluate potential alterations for sweetened-fat preference. No long-term FLX-induced differences in preference for sweetened fat versus chow, nor total caloric intake, were noted; however, females displayed higher preference for sweetened fat compared to males. In Experiment 2, PND35 male rats received FLX (PND35-49) and were exposed to chronic variable stress (CVS) in adulthood (PND74-88). During treatment, FLX decreased body weight and intake (meal size), but not total meal number. Also, no differences in meal pattern parameters were observed after FLX completion. Likewise, no differences in meal pattern parameters to a palatable diet (45% fat, 17% sucrose) presented from PND74 to PND88, even after CVS, were observed. Our findings indicate that juvenile FLX reduces body weight gain acutely via reduced meal size intake; however, no long-term changes in ad libitum feeding behavior or binge access to a palatable stimulus are evident.
Asunto(s)
Conducta Alimentaria , Fluoxetina , Ratas , Masculino , Femenino , Animales , Fluoxetina/farmacología , Ratas Sprague-Dawley , Dieta , Peso CorporalRESUMEN
Mania is a serious neuropsychiatric condition associated with significant morbidity and mortality. Previous studies have suggested that environmental exposures can contribute to mania pathogenesis. We measured dietary exposures in a cohort of individuals with mania and other psychiatric disorders as well as in control individuals without a psychiatric disorder. We found that a history of eating nitrated dry cured meat but not other meat or fish products was strongly and independently associated with current mania (adjusted odds ratio 3.49, 95% confidence interval (CI) 2.24-5.45, p < 8.97 × 10-8). Lower odds of association were found between eating nitrated dry cured meat and other psychiatric disorders. We further found that the feeding of meat preparations with added nitrate to rats resulted in hyperactivity reminiscent of human mania, alterations in brain pathways that have been implicated in human bipolar disorder, and changes in intestinal microbiota. These findings may lead to new methods for preventing mania and for developing novel therapeutic interventions.
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Manía/fisiopatología , Productos de la Carne/efectos adversos , Nitratos/efectos adversos , Adulto , Animales , Trastorno Bipolar/etiología , Trastorno Bipolar/metabolismo , Trastorno Bipolar/fisiopatología , Encéfalo/fisiopatología , Femenino , Humanos , Hipercinesia/metabolismo , Masculino , Manía/etiología , Manía/metabolismo , Productos de la Carne/análisis , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: Patients with Anorexia Nervosa (AN) display increased levels of oxidative stress that correlates with disease severity. Unfortunately, the biological ramifications of AN-induced oxidative stress on the brain are largely unknown. Our lab uses the preclinical activity-based anorexia (ABA) paradigm to model symptoms of AN. The goal of the present study was to determine how ABA experience affects oxidative state and its consequences in adolescent female rats. METHOD: We compared systemic glutathione and cysteine plasma concentrations and medial prefrontal cortex (mPFC) mitochondrial fission in ABA animals at maximum weight loss or following 10-days of weight recovery to levels in age-matched sedentary (SED) control rats. RESULTS: ABA animals at maximum weight loss had significantly lower plasma levels of cysteine and glutathione compared to SED controls. Additionally, ABA animals at max weight loss have significantly more mPFC mitochondrial fission. There were no significant differences in plasma analyte levels or mitochondrial fission between weight recovered ABA animals and SED controls. DISCUSSION: These data suggest that ABA experience results in oxidative stress that is remedied after weight restoration. The long-lasting ramifications of transient periods of increased oxidative stress are unknown and can lead to significant consequences on brain function and behavior.
Asunto(s)
Anorexia Nerviosa , Anorexia , Animales , Modelos Animales de Enfermedad , Femenino , Humanos , Dinámicas Mitocondriales , Estrés Oxidativo , Ratas , Pérdida de PesoRESUMEN
BACKGROUND: Cognitive deficits are observed in individuals with obesity. While bariatric surgery can reverse these deficits, it remains unclear whether surgery type differentially influences cognitive outcome. We compared the extent to which vertical sleeve gastrectomy (VSG) and Roux-en Y gastric bypass (RYGB) ameliorated cognitive impairments associated with obesity. METHODS: Female participants approved for VSG (N = 18) or RYGB (N = 18) were administered cognitive measures spanning the domains of attention [Hopkins Verbal Learning Test (HVLT) Trial 1 and Letter Number Sequencing], processing speed [Stroop Color Trial, Symbol Digit Modalities Test, and Trail Making Part A], memory [HVLT Retained and HVLT Discrimination Index], and executive functioning (Stroop Color Word Trials and Trail Making Part B-A) prior to surgery and at 2 weeks and 3 months following surgery. Scores for each cognitive domain were calculated and compared between surgical cohorts using repeated measures analyses of variance. RESULTS: Significant weight loss was observed 2 weeks and 3 months following RYGB and VSG and was accompanied by improvements in processing speed and executive functioning. Patients who received RYGB also experienced improved attention as early as 2 weeks, which persisted at 3 months. This was not observed in individuals who underwent VSG. No changes in memory were observed from baseline measures in either group. CONCLUSIONS: This is the first report of cognitive improvements following VSG and the first direct comparison of cognitive improvements following RYGB and VSG. Short-term improvements in specific domains of cognitive function are observed at the beginning of the active weight loss phase following bariatric surgery that persisted to 3 months. The anatomical distinction between the two surgeries and resulting differential metabolic profiles may be responsible for the improvements in attention observed following RYGB but not following VSG.
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Cognición , Gastrectomía/métodos , Derivación Gástrica/métodos , Obesidad/psicología , Obesidad/cirugía , Adulto , Cirugía Bariátrica/métodos , Índice de Masa Corporal , Función Ejecutiva/fisiología , Femenino , Humanos , Masculino , Periodo Posoperatorio , Pérdida de PesoRESUMEN
BACKGROUND: While bariatric surgery is well established as a means of inducing sustained weight loss, the rate of weight loss typically declines after a year, and weight regain has been observed. Preoperative taste preferences have been suspected to play a role in weight regain, possibly by influencing post-operative dietary practices. We sought to investigate the association between preoperative taste preferences and weight regain following bariatric surgery. METHODS: Patients who underwent bariatric surgery with at least 2 years of follow-up were included. Demographics and weight were collected in follow-up visits; while patient recall of preoperative taste preference was assessed, using a multiple-choice question in the study survey administered at least 6 months post-surgery. Weight regain was calculated as weight at 2 years minus weight at 1 year post-surgery, with weight regain denoted by positive values and weight loss by negative. Linear regression models were utilized to study associations between weight regain and preoperative taste preferences with and without adjusting for demographic factors and surgery type. RESULTS: Patients undergoing RYGB had less weight regain (- 4.5 kg, p = 0.033) compared to patients undergoing VSG. Compared to patients with no preferences, patients with sweet food or salty food preferences had 5.5 kg (p = 0.038) and 6.1 kg (p = 0.048) weight regain, respectively, at 2 years post-surgery. After adjustment, patients with salty food preference had 6.8 kg (p = 0.027) weight regain compared to patients with no preferences. CONCLUSIONS: Preoperative salty taste preference was associated with weight regain at 2 years post-surgery in patients undergoing bariatric surgery. Findings of this project might have implications for predicting long-term weight loss maintenance for patients with known preoperative taste preferences. Our study suggests that patients with preoperative salty taste preference may need further post-operative psychosocial support and resources to prevent weight regain and to ensure healthy and sufficient weight loss.
Asunto(s)
Cirugía Bariátrica/métodos , Preferencias Alimentarias/psicología , Gusto/fisiología , Aumento de Peso/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Encuestas y CuestionariosRESUMEN
A role for the cytoplasmic protein synphilin-1 in regulating energy balance has been demonstrated recently. Expression of synphilin-1 increases ATP levels in cultured cells. However, the mechanism by which synphilin-1 alters cellular energy status is unknown. Here, we used cell models and biochemical approaches to investigate the cellular functions of synphilin-1 on the AMP-activated protein kinase (AMPK) signaling pathway, which may affect energy balance. Overexpression of synphilin-1 increased AMPK phosphorylation (activation). Moreover, synphilin-1 interacted with AMPK by co-immunoprecipitation and GST (glutathione S-transferase) pull-down assays. Knockdown of synphilin-1 reduced AMPK phosphorylation. Overexpression of synphilin-1 also altered AMPK downstream signaling, i.e., a decrease in acetyl CoA carboxylase (ACC) phosphorylation, and an increase in p70S6K phosphorylation. Treatment of compound C (an AMPK inhibitor) reduced synphilin-1 binding with AMPK. In addition, compound C diminished synphilin-1-induced AMPK phosphorylation, and the increase in cellular ATP (adenosine triphosphate) levels. Our results demonstrated that synphilin-1 couples with AMPK, and they exert mutual effects on each other to regulate cellular energy status. These findings not only identify novel cellular actions of synphilin-1, but also provide new insights into the roles of synphilin-1 in regulating energy currency, ATP.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Adenosina Trifosfato/metabolismo , Proteínas Portadoras/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Acetil-CoA Carboxilasa/metabolismo , Células HEK293 , Humanos , Fosforilación , Unión Proteica , Pirazoles/farmacología , Pirimidinas/farmacología , Transducción de Señal/efectos de los fármacosRESUMEN
Background Bariatric embolization is a new endovascular procedure to treat patients with obesity. However, the safety and efficacy of bariatric embolization are unknown. Purpose To evaluate the safety and efficacy of bariatric embolization in severely obese adults at up to 12 months after the procedure. Materials and Methods For this prospective study (NCT0216512 on ClinicalTrials.gov ), 20 participants (16 women) aged 27-68 years (mean ± standard deviation, 44 years ± 11) with mean body mass index of 45 ± 4.1 were enrolled at two institutions from June 2014 to February 2018. Transarterial embolization of the gastric fundus was performed using 300- to 500-µm embolic microspheres. Primary end points were 30-day adverse events and weight loss at up to 12 months. Secondary end points at up to 12 months included technical feasibility, health-related quality of life (Short Form-36 Health Survey ([SF-36]), impact of weight on quality of life (IWQOL-Lite), and hunger or appetite using a visual assessment scale. Analysis of outcomes was performed by using one-sample t tests and other exploratory statistics. Results Bariatric embolization was performed successfully for all participants with no major adverse events. Eight participants had a total of 11 minor adverse events. Mean excess weight loss was 8.2% (95% confidence interval [CI]: 6.3%, 10%; P < .001) at 1 month, 11.5% (95% CI: 8.7%, 14%; P < .001) at 3 months, 12.8% (95% CI: 8.3%, 17%; P < .001) at 6 months, and 11.5% (95% CI: 6.8%, 16%; P < .001) at 12 months. From baseline to 12 months, mean SF-36 scores increased (mental component summary, from 46 ± 11 to 50 ± 10, P = .44; physical component summary, from 46 ± 8.0 to 50 ± 9.3, P = .15) and mean IWQOL-Lite scores increased from 57 ± 18 to 77 ± 18 (P < .001). Hunger or appetite decreased for 4 weeks after embolization and increased thereafter, without reaching pre-embolization levels. Conclusion Bariatric embolization is well tolerated in severely obese adults, inducing appetite suppression and weight loss for up to 12 months. Published under a CC BY-NC-ND 4.0 license. Online supplemental material is available for this article.
Asunto(s)
Cirugía Bariátrica , Embolización Terapéutica , Obesidad/cirugía , Adulto , Anciano , Cirugía Bariátrica/efectos adversos , Cirugía Bariátrica/métodos , Cirugía Bariátrica/estadística & datos numéricos , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/métodos , Embolización Terapéutica/estadística & datos numéricos , Endoscopía Gastrointestinal , Femenino , Fundus Gástrico/irrigación sanguínea , Fundus Gástrico/diagnóstico por imagen , Fundus Gástrico/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Pérdida de Peso/fisiologíaRESUMEN
BACKGROUND: Pre-treatment with the corticotropin-releasing factor antagonist α-helical CRF9-41 prevents inhibition of gastric emptying by cocaine-and amphetamine-regulated transcript peptide at a dorsal hindbrain level, but its inhibition of sucrose intake is not affected. This is suggestive of separable underlying mechanisms of action in the caudal brainstem for cocaine-and amphetamine-regulated transcript peptide with regard to food intake and gastrointestinal functions. Here we further examine cocaine-and amphetamine-regulated transcript peptide-corticotropin-releasing factor receptor interactions in caudal brainstem controls of solid food intake. Injections of combinations of vehicle, cocaine-and amphetamine-regulated transcript peptide (0.5 µg or 1 µg) or α-helical CRF9-41 were given into the fourth cerebral ventricle of rats. Nocturnal solid food intake was recorded over 22 h. RESULTS: Pre-treatment with α-helical CRF9-41 into the fourth ventricle significantly increased the responsivity to cocaine-and amphetamine-regulated transcript peptide on hypophagia. In a separate control experiment, α-helical CRF9-41 pre-treatment blocked CRF-induced food intake inhibition indicative of its antagonistic effectiveness. CONCLUSIONS: We conclude that an endogenous Corticotropin-releasing factor agonist may modulate suppression of food intake caused by cocaine-and amphetamine-regulated transcript peptide at a dorsal hindbrain level in the absence of stress. A potential caudal brainstem mechanism whereby cocaine-and amphetamine-regulated transcript peptide effects on food intake is attenuated via corticotropin-releasing factor receptor activity causing tonic inhibition, is suggested.
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Fármacos del Sistema Nervioso Central/farmacología , Hormona Liberadora de Corticotropina/antagonistas & inhibidores , Ingestión de Alimentos/efectos de los fármacos , Proteínas del Tejido Nervioso/farmacología , Fragmentos de Péptidos/farmacología , Rombencéfalo/efectos de los fármacos , Animales , Hormona Liberadora de Corticotropina/metabolismo , Hormona Liberadora de Corticotropina/farmacología , Ingestión de Alimentos/fisiología , Cuarto Ventrículo , Inyecciones Intraventriculares , Masculino , Proteínas del Tejido Nervioso/metabolismo , Fragmentos de Péptidos/metabolismo , Ratas Sprague-Dawley , Rombencéfalo/metabolismoRESUMEN
BACKGROUND: Appetitive characteristics are an important factor in the nutritional status of children with cystic fibrosis (CF). We administered a brief parent-report eating behavior questionnaire, validated in healthy children, to determine the relationship between appetitive characteristics and body weight in children with CF. METHODS: Parents of children attending the Johns Hopkins Pediatric CF Clinic completed the Child Eating Behavior Questionnaire (CEBQ) at a routine clinic visit. Responses were correlated with anthropometric and other clinical data. RESULTS: Parents of 64 children with CF aged 7.74⯱â¯3.17 years (mean⯱â¯SD) completed the CEBQ. The CEBQ subscales demonstrated good internal consistency (Cronbach's αâ¯=â¯0.76-0.94). Higher scores on food avoidance subscales (Slowness in Eating) were associated with lower body mass index (BMI) z-scores, and higher scores on food approach subscales (Food Responsiveness, Enjoyment of Food, Emotional Overeating) with higher BMI z-scores. Children with feeding aids (i.e. gastric tube or appetite-stimulating medications) demonstrated greater food avoidance (Slowness in Eating) and lesser food approach (Enjoyment of Food) when compared to those without feeding aids. Children with pancreatic insufficiency also demonstrated greater food avoidance (Slowness in Eating). CONCLUSIONS: The CEBQ can be used in a clinical setting to identify children with CF with appetitive characteristics associated with difficulty gaining weight. These children could potentially benefit from earlier interventions to aid in weight gain. Characterization of appetite using the CEBQ could aid investigation of the biological etiology of low appetite, and optimization of clinical and parental approaches to achieving a healthy nutritional status.
Asunto(s)
Fibrosis Quística/psicología , Conducta Alimentaria/psicología , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Evaluación Nutricional , Encuestas y Cuestionarios/normas , Adulto , Apetito , Índice de Masa Corporal , Niño , Conducta Infantil , Preescolar , Fibrosis Quística/fisiopatología , Trastornos de Alimentación y de la Ingestión de Alimentos/etiología , Femenino , Humanos , Masculino , Estado Nutricional , Padres/psicología , Reproducibilidad de los ResultadosRESUMEN
Easy access to high-energy food has been linked to high rates of obesity in the world. Understanding the way that access to palatable (high fat or high calorie) food can lead to overconsumption is essential for both preventing and treating obesity. Although the body of studies focused on the effects of high-energy diets is growing, our understanding of how different factors contribute to food choices is not complete. In this study, we present a mathematical model that can predict rat calorie intake to a high-energy diet based on their ingestive behavior to a standard chow diet. Specifically, we propose an equation that describes the relation between the body weight ( W), energy density ( E), time elapsed from the start of diet ( T), and daily calorie intake ( C). We tested our model on two independent data sets. Our results show that the suggested model can predict the calorie intake patterns with high accuracy. Additionally, the only free parameter of our proposed equation (ρ), which is unique to each animal, has a strong correlation with their calorie intake.
Asunto(s)
Conducta Animal , Ingestión de Energía , Metabolismo Energético , Conducta Alimentaria , Modelos Biológicos , Valor Nutritivo , Alimentación Animal , Animales , Peso Corporal , Preferencias Alimentarias , Masculino , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Besides its well-known action to stimulate thyroid hormone release, thyrotropin mRNA is expressed within the brain, and thyrotropin and its receptor have been shown to be present in brain areas that control feeding and gastrointestinal function. Here, the hypothesis that thyrotropin acts on receptors in the hindbrain to alter food intake and/or gastric function was tested. Fourth ventricular injections of thyrotropin (0.06, 0.60, and 6.00 µg) were given to rats with chronic intracerebroventricular cannulas aimed at the fourth ventricle. Thyrotropin produced an acute reduction of sucrose intake (30 min). The highest dose of thyrotropin caused inhibition of overnight solid food intake (22 h). In contrast, subcutaneous administration of corresponding thyrotropin doses had no effect on nutrient intake. The highest effective dose of fourth ventricular thyrotropin (6 µg) did not produce a conditioned flavor avoidance in a standardized two-bottle test, nor did it affect water intake or gastric emptying of glucose. Thyrotropin injected in the fourth ventricle produced a small but significant increase in rectal temperature and lowered plasma levels of tri-iodothyronin but did not affect plasma levels of thyroxine. In addition, there was a tendency toward a reduction in blood glucose 2 h after fourth ventricular thyrotropin injection ( P = 0.056). In conclusion, fourth ventricular thyrotropin specifically inhibits food intake, increases core temperature, and lowers plasma levels of tri-iodothyronin but does not affect gastromotor function.
Asunto(s)
Regulación de la Temperatura Corporal/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Rombencéfalo/efectos de los fármacos , Respuesta de Saciedad/efectos de los fármacos , Tirotropina/administración & dosificación , Animales , Biomarcadores/sangre , Glucemia/metabolismo , Relación Dosis-Respuesta a Droga , Inyecciones Intraventriculares , Masculino , Ratas Sprague-Dawley , Receptores de Tirotropina/agonistas , Receptores de Tirotropina/metabolismo , Rombencéfalo/metabolismo , Factores de Tiempo , Triyodotironina/sangreRESUMEN
The orosensory characteristics of a diet play a role in its acceptance and rejection. The current study was designed to investigate the gustatory components that contribute to the intake of a palatable, high-energy diet (HE; 45% calories from fat, 17% calories from sucrose). Here, rats were conditioned to avoid HE diet by pairings with i.p. injections of LiCl to induce visceral malaise. Subsequently, the degree of generalization was tested to an array of taste compounds using a brief-access lick procedure (10-s trials, 30-min sessions). Compared to NaCl-injected controls, LiCl-injected rats suppressed licking response to 100% linoleic acid and 20% intralipid, and to a lesser extent 17% sucrose. There was more variability in the lick responses to sucrose among the LiCl-injected rats. Rats that tended to suppress licking responses to sucrose generalized this response to glucose, fructose and Na-saccharin but not to Polycose. In contrast, LiCl-injected rats did not significantly suppress lick responses to water, NaCl, citric acid, or quinine compared to controls rats. The brief access feature of this procedure, allows for behavioral measures when postingestive factors are minimized. These findings support a role for gustatory cues in the detection of high fat/high sugar diets. Furthermore, it appears that the fat component is a more salient orosensory feature of the HE diet.