The aim of this thesis was to characterize the expression of the peptides ghrelin and obestatin, as well as other neuroendocrine markers in human normal tissues, in invasive breast cancer and a wide panel of neuroendocrine tumors (NETs). In normal tissues the expression of ghrelin and obestatin was mainly localized to the gastric mucosa, and in lesser extent in the remaining gastrointestinal tract, endocrine pancreas and mammary glands. Double immunofluorescence studies demonstrated that ghrelin and obestatin were co-localized in the same cells displaying the same cytoplasmic distribution. In normal breast tissue, ghrelin, obestatin, adrenomedullin, apelin and vesicular monoamine transporter 2 were specifically demonstrated in the luminal epithelial cells. Consecutive sections indicated that mammary epithelial cells could express several of these peptides. Secretogranin II and III were also detected in breast tissue, but their presence was restricted to the outer layer of myoepithelial cells, whereas chromogranin B immunoreactivity was found in both the epithelial and myoepithelial cells. Ghrelin and obestatin immunoreactivity was seen in invasive breast cancer, where the expression could be correlated to factors associated with prognosis. Furthermore, multivariate analysis indicated that ghrelin expression was a possible independent prognostic factor for prolonged recurrence-free and breast cancer-specific survival. In a panel of NETs and endocrine-related disorders it was revealed that ghrelin and obestatin immunoreactivity was primarily found in tumors originating from the respective normal tissues. The two proteins were detected in only a few cases and only occasional tumor cells were immunoreactive. In conclusion, ghrelin and obestatin are localized in the gastrointestinal tract, endocrine pancreas and mammary glands. This thesis has contributed to our understanding of the distribution of ghrelin and obestatin in both normal tissue and tumor cells. A potential role of ghrelin as a prognostic factor in invasive breast cancer has been identified and should be further explored.

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Feeding behavior is a complex phenomenon involving homeostatic signals, and non-homeostatic inputs such as visual cues. In primates, exposure to food-related sensory cues has been shown to elicit cephalic phase responses as well as trigger central appetitive processing, in a motivationally-dependent manner. Neural structures consistently implicated in such responses and/or in the regulation of ingestive behavior in general, in both monkeys and in humans, include the amygdala, insula, striatum, hypothalamus, and frontal and occipital cortices. In humans however, the cerebral response to visual food stimulation remains minimally explored. / Functional Magnetic Resonance Imaging (fMRI) provides information about state-dependent changes in local neuronal activity in vivo. Using fMRI, the present dissertation examined changes in human brain activity to food and nonfood pictures following the pharmacological induction of hunger with the orexigenic hormone ghrelin (Study 1), and following manipulation of the cognitive state of food expectation (Study 2). / Our data reinforce the involvement of a distributed frontal-limbic-paralimbic circuit in the central processing of food imagery, under both experimental conditions. The first study revealed that intravenous ghrelin administration potently modulated food-associated neural responses III areas involved in reward, motivation, memory, and attention (amygdala, insula, orbitofrontal cortex, striatum, hippocampus, midbrain, visual areas). This suggests that metabolic signals such as ghrelin may promote food consumption by enhancing the appetitive response to food cues via engagement of the hedonic network. / The second study revealed that brain regions activated in the 'expectant' state (i.e. when subjects were anticipating food reward) were at least partially dissociable from those in the 'not expectant' state. In particular, recruitment of the dorsolateral prefrontal cortex, a principal component in the cognitive control network, exclusively in the 'not expectant' condition, may signal an attempt to suppress appetite in the absence of food expectation. Areas of convergence were observed in the amygdala and insula. / Obesity is rapidly becoming the major cause of excess mortality worldwide; therefore, understanding how the central nervous system controls appetite and nutrient consumption is of considerable interest. The projects in this thesis offer significant insights regarding the effects two select factors (one intrinsic and the other extrinsic) on the neural reaction to visual food stimuli, in healthy male participants.

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Thesis (Ph.D. in Cell & Developmental Biology) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 144-158). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

Τα επίπεδα της γκρελίνης και του PYY μετά από χειρουργείο χολοπαγκρεατικής εκτροπής και Roux-en-Y γαστρικού bypass και μετά από χειρουργείο κολεκτομής: προοπτική συγκριτική μελέτη Οι ορμόνες του γαστρεντερικού γκρελίνη και PYY έχει αποδειχθεί ότι παίζουν κάποιο ρόλο στη ρύθμιση του μεταβολισμού και της όρεξης. Μελετάμε την επίδραση του χειρουργείου της χολοπαγκρεατικής εκτροπής και RYGBP (BPD-RYGBP) στα κυκλοφορούντα επίπεδα της γκρελίνης και του PYY άμεσα μετεγχειρητικά και τα συγκρίνουμε με την αντίστοιχη επίδραση μιας άλλης χειρουργικής επέμβασης της ίδιας βαρύτητας, την κολεκτομή. Μέθοδος. Μελετάμε τα επίπεδα νηστείας της γκρελίνης και του PYY σε 20 παχύσαρκους ασθενείς (super-obese) που υποβλήθηκαν σε BPDRYGBP και σε 13 ασθενείς που υποβλήθηκαν σε κολεκτομή για καρκίνο παχέος εντέρου. Οι μετρήσεις έγιναν προεγχειρητικά, και τις μετεγχειρητικές ημέρες 1,3,7,30 και 90 και στις δύο ομάδες, καθώς και στον 1 χρόνο στην ομάδα των παχυσάρκων. Αποτελέσματα. Προεγχειρητικά, τα επίπεδα και της γκρελίνης και του PYY ήταν χαμηλότερα στην ομάδα των παχυσάρκων. Μια προσωρινή μείωση των τιμών της γκρελίνης παρατηρήθηκε και στις δύο ομάδες άμεσα μετεγχειρητικά με σταδιακή επάνοδο στα προεγχειρητικά επίπεδα έως τον 3ο μήνα. Επιπλέον τα επίπεδα της γκρελίνης αυξήθηκαν 40%, σε σύγκριση με τα προεγχειρητικά, στην ομάδα των παχυσάρκων στον 1ο χρόνο παρακολούθησης. Τα επίπεδα του PYY στην ομάδα των κολεκτομών μειώθηκαν τις πρώτες 3 μετεγχειρητικές ημέρες και έπειτα επέστρεψαν στα προεγχειρητικά. Σε αντίθεση, τα επίπεδα του PYY στην ομάδα των παχυσάρκων δεν άλλαξαν άμεσα μετεγχειρητικά αλλά αυξήθηκαν σε επίπεδα 50% υψηλότερα στον 3ο μήνα και 170% υψηλότερα στον 1ο χρόνο, σε σύγκριση με τα προεγχειρητικά. Συμπεράσματα. Η μεγάλη μετεγχειρητική αύξηση των επιπέδων της ανορεξιογόνου ορμόνης PYY μετά από BPD-RYGBP μπορεί να παίζει ρόλο στην μειωμένη όρεξη που παρατηρείται μετά από αυτό τον τύπο βαριατρικής επέμβασης. Οι αλλαγές της γκρελίνης μετεγχειρητικά κάνουν τη συμμετοχή της ορμόνης αυτής στη μείωση της όρεξης λιγότερο πιθανή. / Ghrelin and Peptide YY levels anfter a variant of biliopancreatic diversion with Roux-en-Y gastric bypass versus after colectomy: A prospective comparative study Background. The gastrointestinal peptide hormones ghrelin and PYY, have been shown to play a role in the regulation of metabolism and apetite. We investigate the effect of the biliopancreatic diversion with Roux-en-Y gastric bypass (BPD-RYGBP) procedure on the circulating levels of ghrelin and PYY during the first 3 months postoperatively as compared to the effects of colectomy, an abdominal operation of similar severity. Methods. We determined the fasting plasma levels of ghrelin and PYY in 20 morbidly super obese patients that underwent BPD-RYGBP and in 13 subjects that underwent a colectomy because of large bowel cancer. Fasting plasma ghrelin and PYY levels were measured preoperatively and during the postoperative period on days 1,3,7,30 and 90 in all patients of both groups and at the 1 year for the patients who had attained 1-year follow up. Results. Preoperatively, both plasma ghrelin and PYY levels were lower in the BPD-RYGBP group of patients. A temporary decrease in plasma ghrelin levels was observed in both groups of patients during the immediate postoperative period with a gradual return to preoperative levels by the third month. In addition, ghrelin concentrations increased at one year to levels 40% higher than those in baseline, in ten of the BPD-RYGBP patients who had completed the one-year follow up (p=0.004). Plasma PYY levels in the colectomy group decreased the first three postoperative days and then returned to baseline. In contrast, PYY levels in the BPD-RYGBP group did not change during the early postopera¬tive period but increased to levels 50% higher at 3 months (p<0.001) and 170% higher at one year (p<0.001) than the baseline. Conclusions. The great postoperative increase of the levels of the anorexigenic peptide PYY following BPD-RYGBP may contribute to the reduced appetite observed after this type of bariatric surgery. The changes in ghrelin levels postoperatively make its contribution to the appetite suppression less likely.

Objetivos: Leptina e grelina são hormonios relacionados a regulação da ingestão alimentar e consequentemente o controle de peso. Como tem sido descrito até agora, os valores normais desses hormônios estão sujeitos a grande variabilidade. Devido a falta de estudos que contemplem os valores totais de grelina total, grelina acilada, leptina, insulina e glicose em crianças, esse estudo tem o objetivo de avaliar esses hormônios e comparar com as variáveis antropométricas em crianças eutróficas de 4 meses a 10 anos. Pacientes e métodos: É um estudo transversal que avaliou 111 crianças de 4 meses a 10 anos de idade. Foram consideradas eutróficas crianças de até 5 anos com valores de IMC para idade entre -2,0 e +2,0 escores-z, e crianças maiores de 5 anos com valores entre -2,0 e +1,0 escores-z, de acordo com a OMS 2009. Os participantes foram selecionados de uma população saudável com pequeno procedimento cirúrgico ou revisão de saúde programada. As crianças foram categorizadas em três grupos: V 24 meses (n = 10); 25-60 meses (n = 22); > 60 meses (n = 27). As amostras de sangue foram coletadas com um jejum mínimo de 3 horas e máximo de 14 horas. As concentrações de grelina total, grelina acilada e leptina foram dosadas pelo kit commercial ELISA (Linco Research, St Charles-MI, US). A concentração de Insulina foi testada com o kit ELISA (Diagnostics System Laboratories, INC Webster-TX, USA) e a de Glicose com o kit comercial GlicosePAP liquiform® (Labtest Diagnóstica – Lagoa Santa-MG, Brasil). Variáveis que apresentaram distribuição normal foram comparadas com o teste t de Student e analizadas com ANOVA, e as que apresentaram distribuição assimétrica foram comparadas pelo teste de Kruskal-Wallis e analizadas pelo teste de Mann-Whitney. As correlações foram testadas pelos coeficientes de Pearson ou Spearman. O nível de significância utilizado foi 0,05. Resultados: A média de idade foi 60 meses (mín-máx 35-91 meses). A mediana (percentis 25-75) dos valores de grelina acilada, grelina total, grelina desacilada, leptina e insulina foram 1,374 pg/ml (949-1,875); 288 pg/ml (212-450); 1,086 pg/ml (711-1,393); 1,53 ng/ml (1,11-2,77) e 15,5 ^U/ml (12,1-23,5), respectivamente. A média ± DP da glicose foi 88,6 ± 13,1. A média do escore-z do IMC/I encontrada foi -0,16 ± 0,78 para meninos e -0,04 ± 0,83 para meninas. Foi encontrada uma correlação inversa da grelina total, acilada e desacilada com a idade [rs= -0,455 (P < 0,001); rs= -0,313 (P = 0,001); rs= -0,484 (P < 0,001)], respectivamente. Ocorreu uma relação direta da leptina com IMC/I e com a idade [(rs = 0,190 (P = 0,046); rs = 0,429 (P < 0,001)], respectivamente. Conclusões: Os resultados observados nas dosagens e as correlações encontradas de grelina com faixa etária e leptina com sexo feminino e parâmetros antropométricos podem ser úteis para comparação com crianças que são portadoras de alterações de apetite. / Objective: Leptin and ghrelin are hormones related to regulation of food intake and consequently body weight control. Normal values of these hormones are subject to a great variability as has been described so far. Due to the lack of studies regarding plasma levels of total and acylated ghrelin and serum levels of leptin, insulin and glucose in young children, this study aimed to assess these hormones and compare with body mass index (BMI) in healthy well-nourish children aged 4 months -10 years old. Methods: Cross-sectional study evaluated 118 children aged 4-129 months old with BMI-for-age values were within -2.0 and +2.0 SD z-scores for children under 5 years and within -2.0 and +1.0 SD for children over five years, according to WHO 2009. Subjects were enrolled from a population referred to minimal surgeries and routine medical check up. All subjects were categorized into 3 groups: d 24 months (n = 10); 25-60 months (n = 22); > 60 months (n = 27). Blood samples were collected following a minimum of 3-hour and a maximum of 14 hours fasting period. Total and acylated ghrelin and leptin concentrations were assessed by ELISA commercial kit (Linco Research, St Charles-MI, US). Insulin was assessed by ELISA commercial kit (Diagnostics System Laboratories, INC Webster-TX, USA) and glucose by ELISA commercial kit GlicosePAP liquiform® (Labtest Diagnóstica – Lagoa Santa-MG, Brazil). Variables with normal distribution were compared by Student´s t test and analysis of variance (ANOVA). Variables with asymmetric distribution were analyzed by Kruskal-Wallis and Mann-Whitney U tests. Correlation between continuous variables was assessed by Pearson or Spearman correlation coefficient test. The level of significance used was 0.05. Results: Total and acyl ghrelin, leptin and glucose were detected in all samples with a median (P 25-75) concentration in the whole group of 1.374 (949-1.875) pg/mL, 288 (212-450) pg/mL, 1.53 (1.11-2.77) ng/mL and 15.5 (12.1-23.5) ^U/mL, respectively. Glucose media ± SD concentration was 88.6 ± 13.1 mg/dL.Conclusions: Ghrelin showed an inverse correlation between and age and leptin a direct correlation between anthropometric parameters and gender in healthy wellnourished children. Insulin and glucose didn’t correlate with any variable.

Introdução e objetivo: Anorexia e desnutrição são causas importantes de desnutrição nas crianças e adolescentes com cirrose. A grelina e a leptina são hormônios envolvidos na homeostase energética, possuem efeitos antagônicos e estão associadas com anorexia em cirróticos. O objetivo deste estudo é avaliar as concentrações de grelina, leptina, insulina e glicose, e o estado nutricional entre crianças e adolescentes cirróticos e hígidos. Métodos: Estudo transversal prospectivo, realizado com 39 crianças e adolescentes com cirrose (66,7% atresia biliar) idade entre 2,5 e 188 meses, sendo 51,3% do sexo feminino e 51,3% eram Child-Pugh A; 41%, B e 7,7%, C respectivamente, e 39 controles hígidos pareados por sexo e idade. As concentrações de grelina, leptina, insulina e glicose foram dosadas pelo método de ELISA. Amostras de sangue foram coletadas pelo menos após 3 horas de jejum. A gravidade da doença hepática foi avaliada pela classificação de Child-Pugh e pelo escore PELD e/ou MELD. A avaliação antropométrica foi realizada pelos índices de estatura para idade, prega cutânea tricipital e a classificação foi determinada de acordo com os padrões WHO 2009 e Frisancho 2008. Resultados: A grelina apresentou correlação inversa com a idade. Os valores medianos (percentil 25-75) de grelina acilada foram significativamente menores nos cirróticos do que nos controles [140,3 (93,9-269,7) pg/ml versus 277,8 (209,9-557,8) pg/ml, P=0,003]. Os valores medianos da grelina total e desacilada dos cirróticos foram 913,4 pg/ml (760,8- 1443,7) e 1397,8 pg/ml (815,27-2.047) respectivamente. Os valores medianos da leptina, insulina e glicose não foram significativamente diferentes entre os cirróticos e os controles (P=0,421; P=0,908; P=0,851). A grelina acilada foi associada com a gravidade e classificação de Child-Pugh, e a grelina desacilada com o escore PELD `15. A leptina apresentou correlação positiva com os parâmetros antropométicos, hematócrito e hemoglobina. Os cirróticos desnutridos apresentaram níveis diminuídos de leptina quando comparados aos cirróticos bem nutridos (P=0,023). Conclusões: A concentração diminuída de grelina acilada e aumentada de grelina total e desacilada relacionaram-se com a gravidade da doença hepática, enquanto os níveis séricos de leptina com desnutrição em crianças e adolescentes cirróticos. A insulina e a glicose não apresentaram associação com as variáveis estudadas. / Introduction and Objective: Anorexia and undernutrition state are a problem of paramount importance in children and adolescents with cirrhosis. Ghrelin and leptin are the main hormones involved in the control of food intake and body weigth, having antagonic effects and being associated with anorexia in cirrhotic patients. This study aimed to investigate the relationship between fasting ghrelin, leptin, insulin and glucose concentrations; and the nutritional status in pediatric cirrhotic patients, comparing with sex- and age-matched healthy controls. Methods: Cross-sectional study evaluated 39 children with cirrhosis (biliary atresia as etiology in 66.7%) aged between 2.5 and 188 months, 51.3% female were evaluated, 51.3% were Child-Pugh A; 41%, B and 7.7%, C. Other 39 healthy children matched for sex and age, taken as controls, were also evaluated. Blood samples were collected at least after 3-hours fasting. Fasting total ghrelin, acyl grelin, leptin, insulin and glucose levels were measured using a commercial ELISA kit. Severity of liver disease was assessed by Child-Pugh classification, and PELD or MELD score. Antropometric papameters including, body fat mass and height for age were determined and classified according to WHO 2009 and Frisancho 2008 standard reference. Results: Plasma ghrelin levels showed an inverse correlation with age. Median values (25-75 centile) of acylated ghrelin were significantly lower in cirrhotics than in healthy controls [142 (93-278) pg/ml vs 275 (208-481) pg/ml, P=0.001]. Median values of leptin, insulin and glucose were not significantly different between cirrhotics and controls (P=0.421; P=0.908; P=0.851). Ghrelin levels were associated with the severity of Child-Pugh classification and PELD or MELD scores `15. Ghrelin levels did not associate with gender and causes of cirrhosis. Leptin levels were correlated positively with anthropometric parameters, hematocrit and hemoglobin. Undernourished cirrhotic patients had lower leptin levels than wellnourished (P=0.023). Conclusion: Plasma acyl ghrelin concentration are lower and total and desacyl ghrelin were higher and associated with cirrhosis severity, whereas leptin was associated with undernourishment in children and adolescents with cirrhosis. Insulin and glucosis werent associated with any variable.

INTRODUÇÃO: A doença de Gaucher (DG) é um erro inato do metabolismo causado pela atividade deficiente da enzima glicocerebrosidase e subdivide-se em três tipos: tipo I (DG tipo I), que é o mais frequente e não apresenta comprometimento do sistema nervoso central; o II (DG tipo II), agudo e neuronopático; e o III (DG tipo III), subagudo e neuropático. Todos os tipos caracterizam-se pela heterogeneidade clínica, com manifestações de intensidade distintas, tais como: hepatoesplenomegalia, alterações hematológicas e dores ósseas. Alterações no metabolismo energético também são descritas. A terapia de escolha para a DG é a reposição enzimática (TRE). OBJETIVO PRINCIPAL: Avaliar o estado nutricional e a homeostase de energia em pacientes com DG em TRE. MÉTODOS: A presente tese contemplou 4 etapas: Etapa 1) Elaboração de revisão sistemática da literatura sobre aspectos nutricionais da DG tipo I. Etapa 2) Avaliação da coorte de pacientes acompanhados no Centro de Referência para DG do Rio Grande do Sul (CRDG/RS; n= 38; DG tipo I=35; DG tipo III= 3) quanto a dados relativos ao estado nutricional. Etapa 3) Avaliação do gasto energético basal por calorimetria indireta dos pacientes com DG tipo III do CRDG/RS. Etapa 4) Avaliação, por meio de estudo transversal controlado, dos níveis de grelina, leptina e adiponectina de pacientes com DG tipo I do CRDG/RS, com idade superior a 18 anos e em TRE há mais de 6 meses (n=15); os pacientes foram pareado por sexo, idade e IMC com controles hígidos. RESULTADOS: Etapa 1) Foram localizados 175 estudos, dos quais 28 preencheram os critérios de inclusão. Etapa 2) Avaliação da coorte de pacientes acompanhados no Centro de Referência para DG do Rio Grande do Sul (CRDG/RS; n= 38; DG tipo I=35; DG tipo III= 3) quanto a dados relativos ao estado nutricional. Etapa 2) Os dados antropométricos dos pacientes adultos com DG tipo I (n=31) revelaram que quatorze apresentavam sobrepeso ou obesidade grau I e todos os pacientes com idade inferior a 18 anos estavam com peso e estatura adequados. A idade dos pacientes apresentou alta correlação com o IMC e com o nível de ferritina. O IMC apresentou correlação com a ferritina e esta com o colesterol total e com o LDL-colesterol. O colesterol total apresentou correlação com o HDL, com o LDL e uma correlação negativa com a quitotriosidase. O subgrupo que iniciou o tratamento com idade superior a 18 anos (n=16) teve um aumento significativo de IMC após a TRE (p=0,001) e o que iniciou o tratamento antes de 16 anos (n=10) teve um aumento significativo no escore-z para estatura e IMC (p=0,004 e p= 0,032, respectivamente). Etapa 3) Os pacientes com DG tipo III apresentaram hipermetabolismo e dois deles estavam desnutridos. Etapa 4) A mediana dos níveis de grelina, leptina e adiponectina dos pacientes não diferiu da dos controles. Os níveis de grelina e adiponectina apresentaram correlação positiva entre si e com o HDL-colesterol; e inversa com o IMC, circunferência de cintura e triglicerídeos. Os níveis de leptina apresentaram correlação inversa com o LDL-colesterol e direta com o IMC, circunferência da cintura, dose de enzima, triglicerídeos, insulina e HOMA-IR. Oito pacientes preenchiam os critérios para síndrome metabólica, quatro dos quais estavam com resistência à insulina pelo índice HOMA-IR. CONCLUSÕES: Os dados da revisão sistemática indicaram que o tratamento com imiglucerase melhora os índices de crescimento de crianças e adolescentes com DG tipo I o que está em consonância com os dados encontrados nesta coorte. Em relação aos pacientes avaliados, o estado nutricional classificado pelo IMC mostrou que quase metade dos pacientes com DG tipo I estava com excesso de peso e que a TRE parece contribuir para esse achado. O hipermetabolismo em pacientes com DG tipo III parece constituir-se num biomarcador da gravidade da doença. A leptina apresentou alta associação com a insulina e com o índice HOMA-IR, podendo tornar-se um biomarcador para avaliar indícios precoces de resistência à insulina em pacientes com DG. Aumento de peso, síndrome metabólica e resistência à insulina parecem ser frequentes em pacientes com DG tipo I. Estudos adicionais são necessários para investigar as associações encontradas. / INTRODUCTION: Gaucher disease (GD) is an inborn error of metabolism, caused by the deficient activity of the glucocerebrosidase enzyme and is divided into three types: type I, which is the most frequent and does not present neurological compromise; type II, which is acute and neuronopathic; and type III, which is subacute and neuronopathic. All types are characterized by clinical heterogeneity and symptomatic manifestations of varied intensity, such as hepatosplenomegaly, hematologic dysfunction, bone pain; energy homeostasis dysfunction is also present. The choice therapy for GD is enzyme replacement therapy (ERT). OBJECTIVE.To assess the nutritional status and the energy homeostasis in patients affected by Gaucher Disease under enzyme replacement therapy. METHODS.This present study is composed of 4 stages. Stage 1) Systematic literature review on GD type I nutritional aspects. Stage 2) Assessment of data revolving around nutritional status of the patients cohort followed at the GD Reference Center in Rio Grande do Sul(CRDG/RS; n= 38; GD type I=35; GD type III= 3. Stage 3) Assessment of basal energetic expenditure by indirect calorimetry in GD type III patients at CRDG/RS. Stage 4) Assessment, by means of controlled transversal study, of ghrelin, leptin and adiponectin levels in GD- I patients, age over 18 yo and under ERT for at least 6 months (n=15); the patients were pair matched with healthy controls for sex, age and BMI. RESULTS: Stage 1) 175 studies were found, of which 28 met the inclusion criteria. These studies have shown ERT is associated to: growth normalization in children and teenagers with delayed development; partial correction of hypermetabolism and glycemic profile dysfunctions; and increase in weight as well as insulin resistance and development of Diabetes mellitus type 2 in adults. Stage 2) The anthropometric data of adult patients with GD type I (n=31) pointed out fourteen showed overweight or obesity level 1, and all patients aged under 18yo showed adequate weight and height. The patient’s age showed high correlation with BMI and ferritin levels. BMI presented correlation with ferritin and the latter with total cholesterol and LDL- cholesterol. Total cholesterol showed correlation with HDL, with LDL and negative correlation with chitotriosidase. The subgroup comprising those who were over 18 years of age (n=16) at the beginning of treatment had a significant increase in BMI after ERT (p=0,001) and those beginning treatment under the age of 16 showed (n=10) significant increase in the z-score for height and BMI (p=0,004 and p= 0,032, respectively). Stage 3) GD type III patients showed hypermetabolism and two of them (2/3) were malnourished. Stage 4) The median of ghrelin, leptin and adiponectin levels of patients did not differ from that of the controls. The ghrelin and adiponectin levels presented positive correlation between themselves, with HDL-cholesterol, and inverse correlation with BMI, waist circumference, and triglycerides. The leptin levels presented inverse correlation with LDL-cholesterol and direct correlation with BMI, waist circumference, enzyme dose, triglycerides, insulin, and HOMA-IR. Eight patients (n=15) met the criteria for metabolic syndrome, four of which had insulin resistance, as measured by the HOMA-IR index. DISCUSSION AND CONCLUSIONS: Data from the systematic review showed the treatment with imiglucerase improves growth in children and adolescents with GD type I, this meets the findings in this cohort. In relation to the patients assessed, the nutritional status measured by BMI showed that almost half of the GD type I patients were overweight and that ERT seems to contribute to this finding. Hypermetabolism in GD type III patients seems to be a biomarker of the severity of this disease. Leptin presented high association with insulin and with the HOMA-IR index, and may eventually become a biomarker to evaluate early evidence of insulin resistance in GD patients. Weight increase, metabolic syndrome and insulin resistance seem to be frequent in GD type I patients. Further research is necessary to investigate the findings herein researched.

A obesidade é caracterizada como uma doença crônica na qual há excesso de massa corporal na forma de gordura, resultando em um grande risco de comorbidades. A saúde humana depende da regulação do metabolismo energético, isto é, a relação entre o consumo alimentar e o gasto energético, processo este de integração entre o Sistema Nervoso Central (SNC) e os órgãos periféricos. Alguns estímulos parecem provocar alterações nas concentrações de Nesfatin-1 (NES1) e Grelina Acilada (GRE), peptídeos envolvidos na homeostase energética, como a obesidade, dieta/refeição hiperlipídica e exercício físico. Assim, o objetivo principal do estudo foi verificar e comparar o efeito agudo do exercício aeróbio sobre o apetite e as concentrações plasmáticas de Grelina Acilada e Nesfatin-1 em homens eutróficos e obesos. Na revisão da literatura, os métodos empregados foram pesquisa bibliográfica, culminado com um artigo de hipótese sobre o tema. No estudo original, onze indivíduos eutróficos (EUT) e dez obesos (OB), sedentários, participaram de 2 protocolos: Controle (Con) e Exercício (Ex). No Ex, os participantes pedalaram durante 45 minutos a 50% do VO2max e, logo após, receberam uma refeição hiperlipídica e permaneceram em repouso por mais 120 minutos. No Con, os participantes ficaram em repouso durante todo o período. Cinco coletas sanguíneas foram realizadas, em cada protocolo. Os níveis de GRE, NES1, triglicerídeos (TG), colesterol total (CT), HDL, LDL e glicose foram mensurados. O apetite (sensação de fome) foi avaliado por meio de uma escala visual. O exercício foi capaz de suprimir os níveis de GRE e apetite nos EUT, mas não nos OB, logo após a sessão. Não houve alteração de NES1 ao longo dos protocolos. Houve uma correlação inversa entre as concentrações plasmáticas em jejum de GRE e NES1 (somente nos EUT) e associação positiva de NES1 com IMC (para ambos os grupos). Este estudo mostrou que o exercício aeróbio agudo induziu supressão de GRE e do apetite em EUT, o que não ocorre em OB. Deste modo, refeições contendo grandes quantidades de gorduras devem ser desencorajadas nesta população. / Obesity is characterized as a chronic disease which there is an excess of body mass as fat, resulting in a greater risk of comorbidities. Human health depends on the regulation of energy metabolism, i.e. the relationship between food intake and energy expenditure, an integration process between the Central Nervous System (CNS) and peripheral organs. Some stimuli, such as obesity, high fat meal/diet, exercise, cause changes in concentrations of peptides involved in energy homeostasis, such as Nesfatin-1 (NES1) and Acylated Ghrelin (GRE). Thus, the main objective of the study was to determine and compare the acute effect of aerobic exercise on appetite and plasma concentrations of acylated ghrelin and nesfatin-1 in normal weight and obese men. In the literature review, the methods employed were bibliographic research, culminating in a hypothesis article about the topic. In the original study, eleven normal weight (EUT) and ten obese (OB), sedentary, participated in two protocols: control (Con) and exercise (Ex). In Ex, they cycled for 45 minutes at 50% VO2max, and soon after, received a high-fat meal and remained resting for over 120 minutes. In Con, the participants were at rest throughout the whole period. Five blood samples were taken in each protocol. The levels of GRE, NES1, triglycerides (TG), total cholesterol (TC), HDL-cholesterol, LDL-cholesterol and glucose were determined. Appetite (hunger sensation) was assessed using a visual scale. The exercise induced suppression of GRE and appetite levels in EUT but not in OB after the session. There was no change in NES1 over protocols. There was an negative correlation between fasting plasma concentrations of NES1 and GRE (only in EUT) and a positive association with BMI and NES1 (for both groups). This study showed that acute aerobic exercise induced suppression of appetite and GRE in EUT, which does not occur in OB. Thus, meals containing high amounts of fats in this population should be discouraged.