Current treatments for obesity have been unsuccessful. It is essential that a patient-centred approach for obesity management is developed and for this to be successful other diet and lifestyle approaches need to be considered. A systematic review comparing low carbohydrate vs. low fat diets for the treatment of obesity was carried out. It found that low carbohydrate/high protein diets are as effective as, if not better, for treating obesity and cardiovascular disease risk factors. A randomised controlled trial investigating dietary approaches for the treatment of obesity and its co morbidities was carried out. Variables including weight and body composition, cardiovascular risk factors, adipokines, liver and kidney function, and health and lifestyle factors were measured. Those with metabolic syndrome were also examined. It was hypothesised that there are alternative ways of treating obese subjects depending on their phenotype. Those with a higher BMI tend to have a higher carbohydrate intake rather that a higher fat intake so may be better suited to a low carbohydrate/high protein diet rather than the conventional low fat/energy reduced diet. Subjects were initially treated with the standard dietary approach for obesity (health eating, HE) and if not successful after 3 months were randomised to either a very low calorie diet (Lighterlife, LL) or a protein sparing modified fast (PSMF). All three groups showed a significant weight loss and reduced risk for CVD at 12 months. Significant improvements were seen for plasminogen-activated receptor-1, adiponectin, leptin and IL-6 on HE and LL, but only adiponectin significantly improved on the PSMF. Neither diet showed any detrimental effects for those with a healthy liver and kidney function. Quality of life and levels of depression improved at 12 months. Of the 54 subjects with metabolic syndrome at baseline, 12 remained on HE and 32 were randomised to LL and PSMF. This indicates that most subjects did not suit a low fat dietary approach. They were successful at losing weight on LL and PSMF and showed improvement in MS risk factors, and adipokine levels at 12 months. In conclusion, the study demonstrates that a low fat diet may not necessarily be the first line of approach to treat obese subjects with a BMI over 35 kg/m2, including those with MS. A very low calorie diet such as LL or a PSMF may be better suited to the subject.

Abstract available through http://www.fasebj.org/doi/abs/10.1096/fasebj.31.1_supplement.1037.5.

<p>The timing of cell differentiation is important for development and renewal of well functioning organs and tissues. One protein involved in this process is Preadipocyte factor 1 (Pref-1). Most likely, the role of this protein is to maintain cells in an undifferentiated state. </p><p>The work presented in this thesis, has employed the rat as an animal model for the studies of Pref-1. Rat models of obesity (Zucker, ZO) and type II diabetes (Goto-Kakizaki, GK) were used to determine metabolic influence on Pref-1 and adipokine mRNA expression in adipose tissues.</p><p>The Pref-1 cleavage product was purified from rat amniotic fluid and physicochemically characterised. Concentration of Pref-1 in serum, amniotic fluid and urine was determined by ELISA. Soluble Pref-1 and the compartmentalisation of the protein were highly similar to what had previously been demonstrated in mice and humans.</p><p>Immunohistochemistry studies displayed similar staining patterns of Pref-1 in adrenal glands, ovaries and pituitary glands of non-pregnant and pregnant rats. This suggests that pregnancy do not influence the protein expression of Pref-1 in these organs.</p><p>In the GK rats, Pref-1 mRNA was altered and a decrease in the visceral compared to subcutaneous adipose depots was demonstrated, in contrast to the ZO rats. Additionally, adiponectin, leptin, IL-6 and TNF-α mRNA levels were altered in the diabetic strain, indicating that this animal model expresses many of the typical features of type II diabetes.</p><p>In conclusion, the rat is an appropriate model for studies of FA1/Pref-1/dlk. Pref-1 is highly elevated in fetal and maternal serum during pregnancy. However, the expression of Pref-1 in some endocrine tissues did not alter due to pregnancy. The mRNA expression of Pref-1 was altered between adipose depots and demonstrated to be affected by metabolic disturbances in the animals.</p>

There is an increased risk for cardiovascular (CV) comorbidity among patients with rheumatoid arthritis (RA), with premature atherosclerosis, and a higher incidence of CV events, compared with the general population. Disease related factors add to the CV risk, and interact with the traditional CV risk factors. The underlying mechanism for this is not completely understood. In active RA there is a loss of muscle mass and an increase in body fat content. Production of cytokines, i.e., adipokines, in the adipose tissue could link the inflammation with the CV system. Control of the inflammation has been suggested to modify the CV risk in RA, and the recently introduced biological drugs, such as the tumor necrosis factor inhibitors (TNFi), have opened up new treatment opportunities. The aim of this thesis was to evaluate aspects of the interaction between inflammation and CV comorbidity in RA using biochemical and epidemiological methods. Methods In the first two studies, patients with established RA were examined for clinical disease activity, and blood samples were analysed for cytokines and adipokines using ELISAs and multiplex technology. In Study I (n RA=23) anthropometric measurements were assessed and in Study II (n RA=51) measurements of intima-media thickness (IMT), and endothelial function (FMD). From a subgroup of patients (Study II, n RA=13) samples of abdominal subcutaneous adipose tissue (SAT) were analysed for content of adipokines. In study III and IV associations between treatment with TNFi and acute coronary syndromes (ACS) were analysed using data from the Swedish Rheumatology Register; in Study III regarding early RA (n TNFi exposed=1,271, n bionaïve RA=4,729), and in Study IV comprising patients with RA of all stages (n TNFi exposed=7,213, n bionaïve RA=17,769) and with a matched general population comparator cohort (n=32,161). Associations between response to TNFi therapy and risk for ACS in the early RA cohort were evaluated in a nested case-control design (cases n=24, controls n=81). Results Serum levels of the cytokines/adipokines interleukin-1 receptor antagonist (IL-1Ra), IL-6, osteopontin, visfatin and TNF were increased in patients compared with controls (p≤0.001-0.036). The amount of TNF receptor II extracted from SAT was greater in patients (p=0.006). The serum (s-) levels of IL-1Ra correlated with s-leptin (r=0.71, p≤0.001) and s-haptoglobin in RA patients (r=0.56, p≤0.01). The result from a factor analysis indicated IL-1Ra to be associated with both adipose tissue and inflammation. Levels of s-visfatin (p=0.019) and s-IL-1Ra (p=0.023), respectively, were positively associated with IMT independently of inflammatory activity and CV risk factors. PAI-1 and MCP-1 extracted from SAT showed inverse associations with IMT. Patients with RA, whether exposed to TNFi or bio-naïve, had a doubled risk for ACS compared with the general population; HR 2.09 (95%CI 1.58-2.76) and 1.80 (1.49-2.17), respectively. No significant associations between risk for ACS and TNFi exposure were detected after adjustments; HR 0.80 (0.52-1.24) in early RA and HR 1.08 (0.82-1.41) in RA of any duration. Furthermore, no association between the risk for ACS and response to TNFi treatment in patients with early RA was observed, OR 1.5 (0.3-6.9). Conclusions The results indicate that cytokines/adipokines may have a role in the development of atherosclerosis in RA patients. A continuing increase in the risk of ACS in RA compared with the general population, despite modern therapeutic strategies, was noted. Neither exposure nor response to treatment with TNFi was associated with any modification of the risk for ACS.

Les omégas trois ont un bénéfice prouvé dans la prévention de maladie cardiovasculaire et l'inflammation. Un apport optimal peut être réalisé avec des modifications diététiques simples permettant d'avoir un enrichissement des membranes cellulaires et un effet métabolique. Le tissu adipeux de part son rôle important dans la genèse du syndrome métabolique semble être une cible importante du traitement par oméga trois. Les patients avec une maladie rénale chronique (MRC) ont un risque cardiovasculaire accru et cumulent les perturbations métaboliques comme le syndrome métabolique et un état micro inflammatoire. Des doses supra physiologiques d'oméga trois ont été utilisés dans le passé dans des études de prévention rénale ou traitement de dyslipidémie. Or l'effet métabolique en fonction de la dose d'oméga 3 n'est pas connu. En accord, avec les études chez le sujet sain, en fonction de la dose administrée, les omégas 3 ont un impact différent métabolique et sur l'expression génique. Des études complémentaires sont nécessaires pour vérifier la faisabilité et l'impact métabolique d'une modification de régime afin de diminuer le rapport n-6/n-3, ainsi que l'effet à long terme des omégas trois chez ces patients. Par ailleurs, les mécanismes impliqués dans les différences de dose réponse devront être caractérisés sur un modèle animal

Οι λιποκίνες αποτελούν πρωτεϊνικά προϊόντα του λιπώδους ιστού με αυτοκρινείς, παρακρινείς και ενδοκρινείς δράσεις που εμπλέκονται στην παθογένεια της καρδιαγγειακής νόσου. Η τοπική παραγωγή λιποκινών, ειδικά από τον περιαγγειακό λιπώδη ιστό, μπορεί να επηρεάσει τη φυσιολογία και την παθολογία των αγγείων. Το ενδοκανναβινοειδές σύστημα σχετίζεται με τη ρύθμιση της ενδοκρινούς λειτουργίας του λιπώδους ιστού, αλλά και με την παθογένεια της αθηροσκλήρωσης. Μελετήσαμε την έκφραση της αντιπονεκτίνης, της βισφατίνης, της λεπτίνης και των νεότερων λιποκινών χεμερίνης και βασπίνης, καθώς και του υποδοχέα ενδοκανναβινοειδών CB1 σε ανθρώπινο περιαορτικό και επικαρδιακό λιπώδη ιστό, καθώς και τη συσχέτισή τους με την αορτική και τη στεφανιαία αθηροσκλήρωση. Εφαρμόστηκε ανοσοϊστοχημική χρώση για τις λιποκίνες και τον CB1 σε δείγματα ανθρώπινου περιαορτικού, περιστεφανιαίου και επικαρδιακού λίπους της κορυφής της καρδιάς. Οι αθηροσκληρωτικές βλάβες στο παρακείμενο αγγειακό τοίχωμα αξιολογήθηκαν με βάση την κατάταξη του AHA. Οι λιποκίνες εκφράστηκαν στον περιαγγειακό και επικαρδιακό λιπώδη ιστό της κορυφής και – με εξαίρεση την αντιπονεκτίνη – στα αγγειακά λεία μυικά κύτταρα και στα αφρώδη κύτταρα των αθηροσκληρωτικών βλαβών. Ο CB1 εκφράστηκε στον περιαορτικό και επικαρδιακό λιπώδη ιστό, καθώς και στα αορτικά και στεφανιαία αγγειακά λεία μυικά κύτταρα. Η αορτική αθηροσκλήρωση συσχετίστηκε θετικά με την έκφραση της χεμερίνης, της βασπίνης, της βισφατίνης και της λεπτίνης στο περιαορτικό λίπος. Η στεφανιαία αθηροσκλήρωση συσχετίστηκε θετικά με την έκφραση της χεμερίνης και της βασπίνης στο περιστεφανιαίο λίπος. Η έκφραση της αντιπονεκτίνης στο λιπώδη ιστό συσχετίστηκε αρνητικά τόσο με την αορτική όσο και με τη στεφανιαία αθηροσκλήρωση. Η έκφραση λιποκινών στον επικαρδιακό λιπώδη ιστό της κορυφής δε συσχετίστηκε με την αθηροσκλήρωση. Επίσης, η έκφραση του CB1 δε συσχετίστηκε με την αορτική ή με τη στεφανιαία αθηροσκλήρωση. Συμπερασματικά, παρατηρήθηκε: α) διαφορετικό προφίλ έκφρασης της αντιπονεκτίνης, βισφατίνης, λεπτίνης, χεμερίνης, βασπίνης και του CB1 στον περιαορτικό, περιστεφανιαίο και επικαρδιακό λιπώδη ιστό της κορυφής, β) συσχέτιση των λιποκινών, αλλά όχι του CB1, με την αορτική ή και με τη στεφανιαία αθηροσκλήρωση, με χαρακτηριστικό τρόπο για κάθε λιποκίνη. Η τοπική παραγωγή λιποκινών ενδεχομένως επηρεάζει ποικιλοτρόπως την αθηροσκληρωτική διαδικασία σε διαφορετικές θέσεις. / Adipokines are protein products of adipose tissue with autocrine, paracrine and endocrine actions, which have been implicated in the pathogenesis of cardiovascular disease. Locally produced adipokines, especially by periadventitial adipose tissue, may affect vascular physiology and pathology. The endocannabinoid system has also been implicated in the pathogenesis of atherosclerosis and in adipose tissue endocrine function regulation. We investigated the expression of adiponectin, visfatin, leptin and novel adipokines chemerin and vaspin, as well as CB1 endocannabinoid receptor, in human periaortic and epicardial adipose tissue, as well as their correlation to aortic and coronary atherosclerosis. Standard immunohistochemical staining for the adipokines and CB1 was performed on samples of human periaortic, pericoronary and apical epicardial adipose tissue. Atherosclerotic lesions of the adjacent vascular wall were assessed using the AHA classification. Adipokines were expressed in periadventitial and apical epicardial adipose tissue and - except for adiponectin - in vascular smooth muscle cells and foam cells in atherosclerotic lesions. CB1 was expressed in periaortic and epicardial adipose tissue, as well as in aortic and coronary vascular smooth muscle cells. Aortic atherosclerosis was positively correlated with chemerin, vaspin, visfatin and leptin periaortic fat expression. Coronary atherosclerosis was positively correlated with chemerin and visfatin pericoronary fat expression. Adipose tissue adiponectin expression was negatively correlated to atherosclerosis in both locations. Expression of adipokines in apical epicardial fat was not associated to atherosclerosis. CB1 expression was not correlated with either aortic or coronary atherosclerosis. Our results show: a) a different expression pattern of adiponectin, visfatin, leptin, chemerin, vaspin and CB1 in periaortic, pericoronary and apical epicardial adipose tissue, b) a correlation of these adipokines - but not CB1 - with either aortic or coronary atherosclerosis or both in a pattern characteristic for each adipokine and suggest that locally produced adipokines might differently affect the atherosclerotic process in different locations.

Orientador: Aulus Cavalieri Carciofi / Banca: Eduardo Ferriolli / Banca: Silvia Regina Ricci Lucas / Banca: Mirela Tinucci Costa / Banca: Elisabeth Criscuolo Urbinati / Resumo: O aumento dos depósitos corporais de gordura está relacionado com profundas alterações de algumas funções fisiológicas que podem resultar em redução da tolerância à glicose e resistência insulínica. O presente estudo objetivou avaliar os efeitos da perda de peso sobre parâmetros bioquímicos, metabólicos, hormonais e de composição corporal em cães naturalmente obesos, em fase estática a pelo menos 12 meses e após a perda de 20% de peso corporal em comparação com um grupo de cães em condição corporal ideal. O grupo 1 (G1) foi composto por 10 cães obesos com escore de condição corporal igual ou superior a 9 e com porcentagem de gordura corporal média igual a 45,72 ± 1,51%. O grupo 2 (G2) foi composto pelos cães do G1 após a perda de 20% do peso inicial, que passou a apresentar 33,53 ± 1,92% de massa gorda (p<0,001). No grupo 3 (G3), foram incluídos 10 cães da raça beagle, com escore de condição corporal entre 4 e 5, com porcentagem de gordura corporal média igual a 18,36 ± 1,38% (p<0,01). A tolerância à glicose e a sensibilidade insulínica foram avaliados através do teste intravenoso de tolerância à glicose (TIVTG) e pelo teste pós-prandial de glicose e insulina (TPPGI) nos três grupos experimentais. A interação entre tempo e tratamento (grupo experimental) foi significativa para a glicemia (p<0,05), sendo diferentes os grupos G1 x G3 e G2 apresentou valores de glicemia intermediários nos dois testes. No TIVTG, o pico da glicemia nos três grupos experimentais foi observado logo no primeiro minuto após a infusão da glicose. Nos tempos 1,0; 2,5 e 5,0 minutos os valores de glicemia foram estatisticamente menores para G3 em relação à G1. No TPPGI os G1 e G2 apresentaram secreção tardia de insulina, evidenciado por maior área abaixo da curva da insulina no intervalo de 60-360 minutos. Os animais obesos (G1) apresentaram maiores concentrações... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The increase of fat corporal deposits is related with deep alterations of some physiologic functions, which can result in reduction of glucose tolerance and insulin resistance. The present study intended to evaluate the effects of weight loss over different biochemical, metabolic, hormonal and corporal composition parameters in dogs naturally obese, in static phase for at least 12 months, and to compare them after loss of 20% of corporal weight with a group of dogs in ideal corporal condition. The group 1 (G1) was composed by 10 obese dogs with body condition score equal or superior to 9 and with mean corporal fat percentage equal to 45.72 ± 1.51%. Group 2 (G2) was composed by the dogs of G1 after loss of 20% of initial weight, presenting at this moment 33.53 ± 1.92% of corporal fat (p<0.001). In group 3 (G3), 10 beagle dogs were included, with body condition score between 4 and 5, mean percentage of corporal fat equal to 18.36 ± 1.38% (p<0.01). Glucose tolerance and insulin sensibility were measured in the three groups through intravenous glucose tolerance test (TIVTG) and glucose and insulin postprandial test (TPPGI). The interaction between time and treatment (experimental group) was significant for the glycemia (p <0.05), being different the groups G1 x G3 and G2 presented intermediate glycemia values in both tests. In TIVTG, the glycemic peak in the three experimental groups was observed in the first minute after the infusion of glucose. In moments 1.0; 2.5 and 5.0 minutes glycemia values were statistically lower to G3 in comparison to G1. In TPPGI the G1 and G2 groups presented later secretion of insulin, demonstrated for bigger insulin under the curve area from times 60-360 minutes. Obese animals (G1) presented higher serum concentrations of circulating adipokines, leptin, TNF- α and IL-6 than G3 and these values were significantly reduced after weight loss / Doutor

Submitted by isabela.moljf@hotmail.com (isabela.moljf@hotmail.com) on 2017-08-23T11:01:10Z No. of bitstreams: 1 vanessasequeirafontes.pdf: 1540312 bytes, checksum: c76246923c7be32165ca4108f4d08b58 (MD5) / Rejected by Adriana Oliveira (adriana.oliveira@ufjf.edu.br), reason: on 2017-08-24T11:37:33Z (GMT) / Submitted by isabela.moljf@hotmail.com (isabela.moljf@hotmail.com) on 2017-08-24T14:14:43Z No. of bitstreams: 0 / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-08-30T12:41:36Z (GMT) No. of bitstreams: 0 / Made available in DSpace on 2017-08-30T12:41:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-03-10 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / As elevadas prevalências das doenças cardiovasculares (DCV) e seus fatores de risco constituem um desafio aos sistemas de saúde, tornando-se mais relevante na medida em que tais alterações têm aparecido em idades cada vez mais precoces. A inflamação vem sendo reconhecida como um importante elo de ligação entre as DCV, a obesidade e as comorbidades associadas, destacando-se o papel das adipocinas, como a quemerina, substâncias biologicamente ativas secretadas pelo tecido adiposo e que contribuem para a disfunção endotelial. No Brasil, não existem estudos que investiguem tal adipocina na população infanto-juvenil, portanto os objetivos desse trabalho são determinar as concentrações séricas da quemerina em crianças e adolescentes e avaliar sua relação com os fatores de risco para DCV. Foi realizado um estudo epidemiológico transversal com estudantes do ensino fundamental no município de Juiz de Fora/MG. O estudo foi dividido em duas etapas. Na primeira, realizou-se avaliação antropométrica, bioquímica e clínica e, na segunda, selecionou-se aleatoriamente uma subamostra nas quais foram analisados os níveis séricos da quemerina. A participação dos alunos foi voluntária, concedida após a assinatura do Termo de Consentimento Livre e Esclarecido pelos responsáveis e ambas as etapas foram aprovadas pelo Comitê de Ética em Pesquisa com Seres Humanos da Universidade Federal de Juiz de Fora. As análises estatísticas compreenderam os testes T-Student ou Mann-Whitney e qui-quadrado de Pearson. Ao final, calculou-se um modelo de regressão logística. Para a análise dos dados foram utilizados os softwares SPSS® versão 21.0 e STATA® versão 10.1, admitindo-se nível de significância de 5%. A amostra do estudo foi composta por 236 jovens, com média de idade de 10,52 ± 2,05 anos. Dentre os estudantes, 57% apresentavam eutrofia e os níveis séricos de quemerina exibiram média de 218,5 ± 111,35 ng/mL, estando elevado em 14,4% da amostra. As concentrações da adipocina associaram-se com o perímetro de cintura (PC), a insulina e com o índice HOMA-IR. Após a regressão logística, apenas a hiperinsulinemia continuou associada as concentrações elevadas da quemerina. Deste modo, conclui-se que mesmo em uma população jovem e sem complicações metabólicas, os níveis de insulina se mostraram associados as concentrações séricas da quemerina, explicando sua variação. Sabe-se que a hiperinsulinemia é uma das primeiras etapas para o desenvolvimento do diabetes mellitus, logo torna-se importante uma melhor compreensão da atuação da quemerina no desenvolvimento tanto da resistência à insulina quanto de outros fatores relacionados ao risco cardiovascular em crianças e adolescentes e elucidar os mecanismos responsáveis por tais alterações. / The high prevalence of cardiovascular disease (CVD) and its risk factors are a challenge to health systems, becoming more relevant acording as it have appeared at an earlier age. Inflammation has been recognized as an important link between CVD, obesity and associated comorbidities, with emphasis on the role of adipokines, such as chemerin, biologically active substances secreted by adipose tissue and contributing to endothelial dysfunction. In Brazil, there are no studies investigating such adipokine in the child and adolescent population, so the objectives of this study are to determine serum concentrations of chemerin in children and adolescents and to evaluate their relationship with risk factors for CVD. A cross-sectional epidemiological study was realized with primary school students in the city of Juiz de Fora / MG. The study was divided into two stages. In the first, an anthropometric, biochemical and clinical evaluation was performed, and in the second, a sub-sample was selected randomly in which the serum levels of the chemerin were analyzed. The participation of the students was voluntary, granted after the signing of the Term of Free and Informed Consent by those responsible and both stages were approved by the Ethics Committee in Research with Human Beings of the Federal University of Juiz de Fora. Statistical analyzes comprised the Student-T or Mann-Whitney and chi-square tests of Pearson. At the end, a logistic regression model was calculated. Data analysis was performed using software SPSS® version 21.0 and STATA® version 10.1, with a significance level of 5%. The study sample consisted of 236 youngs, with a mean age of 10.52 ± 2.05 years. Among the students, 57% presented eutrophy and the serum levels of chemerin showed a mean of 218.5 ± 111.35 ng / mL, being elevated in 14.4% of the sample. Adipokine concentrations were associated with waist circumference (WC), insulin and the HOMA-IR index. After logistic regression, only hyperinsulinemia continued to be associated with high concentrations of chemerin. Thus, it was concluded that even in a young population with no metabolic complications, insulin levels were shown to be associated with serum concentrations of chemerin, explaining its variation. It is known that hyperinsulinemia is one of the first steps in the development of diabetes mellitus, so is important a better understanding of the role of quemerin in the development of both insulin resistance and other cardiovascular risk factors in children and adolescents and to elucidate the mechanisms responsible for such changes.

The timing of cell differentiation is important for development and renewal of well functioning organs and tissues. One protein involved in this process is Preadipocyte factor 1 (Pref-1). Most likely, the role of this protein is to maintain cells in an undifferentiated state. The work presented in this thesis, has employed the rat as an animal model for the studies of Pref-1. Rat models of obesity (Zucker, ZO) and type II diabetes (Goto-Kakizaki, GK) were used to determine metabolic influence on Pref-1 and adipokine mRNA expression in adipose tissues. The Pref-1 cleavage product was purified from rat amniotic fluid and physicochemically characterised. Concentration of Pref-1 in serum, amniotic fluid and urine was determined by ELISA. Soluble Pref-1 and the compartmentalisation of the protein were highly similar to what had previously been demonstrated in mice and humans. Immunohistochemistry studies displayed similar staining patterns of Pref-1 in adrenal glands, ovaries and pituitary glands of non-pregnant and pregnant rats. This suggests that pregnancy do not influence the protein expression of Pref-1 in these organs. In the GK rats, Pref-1 mRNA was altered and a decrease in the visceral compared to subcutaneous adipose depots was demonstrated, in contrast to the ZO rats. Additionally, adiponectin, leptin, IL-6 and TNF-α mRNA levels were altered in the diabetic strain, indicating that this animal model expresses many of the typical features of type II diabetes. In conclusion, the rat is an appropriate model for studies of FA1/Pref-1/dlk. Pref-1 is highly elevated in fetal and maternal serum during pregnancy. However, the expression of Pref-1 in some endocrine tissues did not alter due to pregnancy. The mRNA expression of Pref-1 was altered between adipose depots and demonstrated to be affected by metabolic disturbances in the animals.

The aim of this study was to assess the dissociation between the presence of cardiovascular risk factors, and the lack of premature atherosclerosis and left venticular hipertrophy (LVH) in isolated GH deficiency (IGHD) due to a mutation in the GH releasing hormone receptor gene. A two step protocol was performed. In the first experiment, serum adiponectin and leptin, and urinary albumin excretion (UAE) were studied in 20 IGHD individuals (7 M/ 13 F; 50,8 ± 14,6 years) and 22 control subjects (C) (8 M/ 14 F; 49,9 ± 11.5 years). IGHD subjects in comparison to C presents high adiponectin levels (p= 0,041) whereas leptin and UAE were similar. In the second experiment, oral glucose tolerance test (1,75 g/Kg in IGHD and 75 g in C) with glucose and insulin mesuarements at 0, 30, 60, 90, 120 e 180 minutes was performed in 24 IGHD subjects (12 M/ 12 F; 39,25 ± 11,73 years) and 25 C subjects (14 M/ 11 F; 39,96 ± 12,49 years). Insulin sensitivity (IS) was assessed by HOMAir, lower values, higher IS; QUICKI, OGIS 2 and OGIS, higher values, higher IS (for the three parameters). Beta cell function was assayed by HOMA-beta, insulinogenic index and area under the curve of the relation between insulin and glucose (AUC I/G). ANOVA indicated glucose response was higher (p<0,0001) and insulin response presented a trend of reduction (p=0,08) in the IGHD gruop. The number of pacients with glucose intolerance was higher (p= 0,001) in the IGHD group. HOMAir was lower (p= 0,041), QUICKI and OGIS 2 showed a trend of elevation (p= 0,066 and p= 0,09, respectively) in the IGHD subjects, whereas OGIS 3 showed no difference between both groups. IGDH presented reduction in HOMA-beta (p= 0,015), insulinogenic index (p<0,0001) and AUC I/G (p=0,02). These different adipokine profile with high adiponectin and normal leptin levels, linked to normal insulin sentitivity may delay vascular damage, LVH and lesions of the renal endothelium (normal UAE). Normal IS and reduced beta cell function featured this IGDH model. / O objetivo deste trabalho foi aprofundar a avaliação da dissociação entre a presença de marcadores de risco cardiovascular (CV) e a ausência de doença CV (DCV) na deficiência isolada do GH (DIGH) por mutação no gene do receptor do hormônio liberador do GH. Foi realizado um protocolo com duas etapas. No primeiro experimento, foram avaliados os níveis séricos de adiponectina e leptina e a excreção urinária de albumina (EUA) em 20 indivíduos com DIGH (7 M/ 13 F; 50,8 ± 14,6 anos) e 22 controles (C) (8 M/ 14 F; 49,9 ± 11.5 anos). Os indivíduos com DIGH em comparação a C apresentaram adiponectina mais elevada (p= 0,041) sem alteração nos níveis de leptina e EUA. No segundo experimento, foi realizado teste de tolerância à glicose oral de glicose (1,75 g/kg no DIGH e 75 g no C) com dosagens de glicose e insulina nos tempos 0, 30, 60, 90, 120 e 180 minutos em 24 indivíduos DIGH (12 M/ 12 F; 39,25 ± 11,73 anos) e 25 C (14 M/ 11 F; 39,96 ± 12,49 anos). A sensibilidade à insulina (SI) foi avaliada pelo HOMAir, onde menores valores, indicam maior SI; e pelos QUICKI, OGIS 2 e OGIS 3, onde maiores valores, indicam maior SI. A função da célula beta foi avaliada pelo HOMA-beta, índice insulinogênico e área sobre a curva da razão insulina/ glicose (ASC I/G). ANOVA indicou que a resposta glicêmica (p< 0,0001) foi maior e a insulinêmica apresentou uma tendência de redução (p= 0,08) no grupo DIGH. O número de pacientes com intolerância à glicose foi maior (p= 0,001) no grupo DIGH. HOMAir foi mais baixo (p= 0,031), e QUICK e OGIS 2 apresentaram uma tendência de elevação (p= 0,066 e p= 0,09, respectivamente) no grupo DIGH, enquanto o OGIS 3 foi semelhante nos dois grupos. DIGH apresentou HOMA-beta (p= 0,015), índice insulinogênico (p< 0,0001) e ASC I/G (p= 0,02) menores. O perfil de adipocinas caracterizado por adiponectina elevada e leptina normal, associado à SI normal pode retardar DCV e disfunção endotelial (EUA normal). SI normal e menor função da célula beta caracterizam este modelo de DIGH.