Introdução: A obesidade infanto juvenil é considerada um grave problema de saúde pública nos países desenvolvidos e em desenvolvimento associando-se a fatores de risco cardiovascular incluindo deposição de gordura abdominal, resistência à insulina (RI), dislipidemia e hipertensão. O tecido adiposo não é mais considerado apenas como um regulador de temperatura corporal ou um protetor mecânico, mas um órgão endócrino que libera adipocinas de ação pró- inflamatória, formando um elo entre adiposidade, síndrome metabólica e doenças cardiovasculares e a inflamação é um estado conseqüente à obesidade. O objetivo deste trabalho foi demonstrar a evolução de adipocinas e do PCRus, ao longo de 12 meses, em crianças obesas usuárias do AmO. Metodologia: Foram acompanhadas crianças e adolescentes em tratamento clínico para obesidade ao longo de 12 meses, avaliados quanto à antropometria, pressão arterial, circunferência de cintura, perfil lipídico, glicemia e insulina jejum, IL6, TNF- α, adiponectina e PCRus em 2 momentos: inclusão e após 12 meses de acompanhamento no AmO. Resultados: Foram avaliadas 27 crianças e adolescentes com mediana de idade de 10,3 anos. Os valores médios do escore-z do IMC baixaram no período (p<0,01), o HDL-c aumentou seus níveis neste período (p= 0,025). As medianas das adipocinas não variaram ao longo de 12 meses: IL-6 (p=0,470), TNF- α (p= 0,753) e adiponectina (p=0,943). 45% da amostra aumentaram seus valores de adiponectina, sendo maior este aumento no sexo feminino. O PCRus baixou ao longo do período (inclusão: 1,67mg/L(IQ:0,53-3,99mg/L); 12 meses: 0,97mg/L(IQ:0,18-2,03mg/L), porém sem diferença estatisticamente significativa p=0,083. Conclusão: As crianças e adolescentes em tratamento clínico para obesidade, após um ano de seguimento, não melhoraram seu perfil de adipocinas, mas baixaram seus valores de mediana de PCRus, embora sem diferença estatisticamente significativa. / Introduction: Obesity in children and adolescents is considered a serious public health problem in developed and developing countries and is associated with cardiovascular risk factors including abdominal fat deposition, insulin resistance (IR), dyslipidemia, and hypertension. Adipose tissue is no longer considered only as a regulator of body temperature or shield mechanic, but an endocrine organ that releases pro-inflammatory adipokines action, forming a link between adiposity, metabolic syndrome and cardiovascular diseases and inflammation is a consequence of the obesity. The objective of this study was to demonstrate the evolution of adipokines and hsCRP over 12 months in obese children users of the AmO (Clinic for Obese Children and Adolescents). Methods: Children and adolescents in clinical treatment for obesity were followed for over 12 months and assessed for anthropometry, blood pressure, waist circumference, lipid profile, fasting glucose and insulin, IL6, TNFalpha, adiponectin, and hsCRP at 2 different times: at inclusion and after a 12-month followup in the AmO. Results: A total of 27 children and adolescents with a median age of 10.3 years old were evaluated. Mean values of BMI z-scores decreased in the period (p <0.01) and HDL-C levels increased during this period (p = 0.025). The median adipokines did not change over 12 months: IL-6 (p= 0.470), TNF-α (p= 0.753), and adiponectin (p = 0.943). 45% of the sample had their adiponectin values increased, being this increase higher in females. The hs CRP lowered over the period (inclusion: 1.67 mg/L (IQ:0.53-3.99m/L) and 12 months: 0.97 mg/L (IQ:0.18-2.03mg/L) but not statistically significant p = 0.083. Conclusion: After a one year follow-up period, children and adolescents in clinical treatment for obesity did not improve their adipokine profile, but lowered their median hsCRP values although there was no statistically significant difference.

Introdução: A obesidade infanto juvenil é considerada um grave problema de saúde pública nos países desenvolvidos e em desenvolvimento associando-se a fatores de risco cardiovascular incluindo deposição de gordura abdominal, resistência à insulina (RI), dislipidemia e hipertensão. O tecido adiposo não é mais considerado apenas como um regulador de temperatura corporal ou um protetor mecânico, mas um órgão endócrino que libera adipocinas de ação pró- inflamatória, formando um elo entre adiposidade, síndrome metabólica e doenças cardiovasculares e a inflamação é um estado conseqüente à obesidade. O objetivo deste trabalho foi demonstrar a evolução de adipocinas e do PCRus, ao longo de 12 meses, em crianças obesas usuárias do AmO. Metodologia: Foram acompanhadas crianças e adolescentes em tratamento clínico para obesidade ao longo de 12 meses, avaliados quanto à antropometria, pressão arterial, circunferência de cintura, perfil lipídico, glicemia e insulina jejum, IL6, TNF- α, adiponectina e PCRus em 2 momentos: inclusão e após 12 meses de acompanhamento no AmO. Resultados: Foram avaliadas 27 crianças e adolescentes com mediana de idade de 10,3 anos. Os valores médios do escore-z do IMC baixaram no período (p<0,01), o HDL-c aumentou seus níveis neste período (p= 0,025). As medianas das adipocinas não variaram ao longo de 12 meses: IL-6 (p=0,470), TNF- α (p= 0,753) e adiponectina (p=0,943). 45% da amostra aumentaram seus valores de adiponectina, sendo maior este aumento no sexo feminino. O PCRus baixou ao longo do período (inclusão: 1,67mg/L(IQ:0,53-3,99mg/L); 12 meses: 0,97mg/L(IQ:0,18-2,03mg/L), porém sem diferença estatisticamente significativa p=0,083. Conclusão: As crianças e adolescentes em tratamento clínico para obesidade, após um ano de seguimento, não melhoraram seu perfil de adipocinas, mas baixaram seus valores de mediana de PCRus, embora sem diferença estatisticamente significativa. / Introduction: Obesity in children and adolescents is considered a serious public health problem in developed and developing countries and is associated with cardiovascular risk factors including abdominal fat deposition, insulin resistance (IR), dyslipidemia, and hypertension. Adipose tissue is no longer considered only as a regulator of body temperature or shield mechanic, but an endocrine organ that releases pro-inflammatory adipokines action, forming a link between adiposity, metabolic syndrome and cardiovascular diseases and inflammation is a consequence of the obesity. The objective of this study was to demonstrate the evolution of adipokines and hsCRP over 12 months in obese children users of the AmO (Clinic for Obese Children and Adolescents). Methods: Children and adolescents in clinical treatment for obesity were followed for over 12 months and assessed for anthropometry, blood pressure, waist circumference, lipid profile, fasting glucose and insulin, IL6, TNFalpha, adiponectin, and hsCRP at 2 different times: at inclusion and after a 12-month followup in the AmO. Results: A total of 27 children and adolescents with a median age of 10.3 years old were evaluated. Mean values of BMI z-scores decreased in the period (p <0.01) and HDL-C levels increased during this period (p = 0.025). The median adipokines did not change over 12 months: IL-6 (p= 0.470), TNF-α (p= 0.753), and adiponectin (p = 0.943). 45% of the sample had their adiponectin values increased, being this increase higher in females. The hs CRP lowered over the period (inclusion: 1.67 mg/L (IQ:0.53-3.99m/L) and 12 months: 0.97 mg/L (IQ:0.18-2.03mg/L) but not statistically significant p = 0.083. Conclusion: After a one year follow-up period, children and adolescents in clinical treatment for obesity did not improve their adipokine profile, but lowered their median hsCRP values although there was no statistically significant difference.

Submitted by Rafael Santana (rafael.silvasantana@ufpe.br) on 2017-04-11T18:25:49Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO MESTRADO RICELLA SOUZA - VERSÃO VIRTUAL.pdf: 2804252 bytes, checksum: da5d4ca93155ec9c8899bcf86b40732a (MD5) / Made available in DSpace on 2017-04-11T18:25:49Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO MESTRADO RICELLA SOUZA - VERSÃO VIRTUAL.pdf: 2804252 bytes, checksum: da5d4ca93155ec9c8899bcf86b40732a (MD5) Previous issue date: 2016-07-04 / O coração humano contém quantidades variáveis de depósitos de gordura. A gordura fisiológica cardíaca ocorre predominantemente no ventrículo direito, estando presente em mais de 50% dos idosos saudáveis. O achado e a caracterização de tecido adiposo ao longo do ventrículo esquerdo têm sido raramente relatados e permanecem pouco conhecidos. Na última década, tem havido crescente evidência da presença de células de gordura no coração esquerdo. Neste intuito, o presente estudo, através do exame necroscópico, buscou: determinar a ocorrência de depósitos de gordura nos compartimentos epicárdico, pericoronariano e miocárdico do ventrículo esquerdo, traçar o perfil epidemiológico e as associações clínicas com esse achado. Dados epidemiológicos, morfológicos e amostras cardíacas foram coletados de 40 cadáveres submetidos a necropsia no Serviço de Verificação de Óbito de Recife, Pernambuco, Brasil. As amostras cardíacas foram fixadas, emblocadas em parafina e submetidas à coloração com hematoxilina–eosina para estudo microscópico. A média de idade dos cadáveres foi de 68,2 anos; 52,2% dos indivíduos tinham histórico de tabagismo; 20% de etilismo; 43,59% dos casos analisados apresentaram causa cardíaca como causa de óbito (o infarto agudo do miocárdio foi a causa imediata de óbito mais frequente) e 82,5% dos cadáveres apresentaram doença aterosclerótica na artéria aorta ascendente. A deposição adiposa no ventrículo esquerdo foi observada em 95% das amostras cardíacas e foi associada com etilismo (Teste de Fisher 0,04; odds ratio [OR] 0.161 [IC 95% 0,072–0,36]; p<0,05); tabagismo (Teste de Fisher 0,508; OR 0.581 [IC 95% 0,431–0,73]; p<0,05); presença do Sinal de Frank (Teste de Fisher 0,502; OR 0.567 [IC 95% 0,414–0,775]; p<0,05); doença aterosclerótica na artéria aorta ascendente (OR 0.774 [IC 95% 0,6405–0,936]; p<0,05); infarto agudo do miocárdio (OR 0.730 [IC 95% 0,600– 0,888]; p<0,05) e achado macroscópico de hipertrofia cardíaca (OR 0.700 [IC 95% 0,525– 0,933]; p<0,05). A deposição de gordura no ventrículo esquerdo cardíaco correlaciona-se com a espessura do coxim adiposo abdominal. Observou-se que a adiposidade epicárdica e a adiposidade pericoronariana constituem as topografias mais frequentes para acúmulo gorduroso na câmara cardíaca esquerda e que o depósito de gordura epicárdico está associado a adiposidade miocárdica (Teste de Fisher 0,019; OR 0.097 [IC 95% 0,033–0,284]; p<0,05). Dessa feita, a deposição adiposa no ventrículo esquerdo é frequente e está associada a fatores de risco de doença cardiovascular. Evidencia-se que a adiposidade cardíaca não pode ser considerada um achado necroscópico aleatório, necessitando de investigação diagnóstica e de mais estudos para averiguação das implicações clínicas. / The human heart contains varying amounts of fat deposits. Cardiac physiological fat occurs predominantly in the right ventricle and is present in over 50% of healthy elderly. The discovery and characterization of adipose tissue along the left ventricle have been reported rarely and remain little known. In the last decade, there has been growing evidence of the presence of fat cells in the left heart. This study, through the autopsy, aimed: to determine the occurrence of fatty deposits in epicardial compartments, pericoronay and myocardial the left ventricle, to trace the epidemiological profile and clinical associations with this finding. Data epidemiological, data morphological and heart samples were collected from 40 corpses autopsied in Death Verification Service of Recife, Pernambuco, Brazil. Cardiac samples were fixed, embedded in paraffin and subjected to hematoxylin-eosin for microscopic study. The mean age of cadavers was 68.2 years, 52.2% of subjects had a history of smoking, 20% alcohol consumption, 43.59% of the cases analyzed showed cardiac cause as a cause of death (acute myocardial infarction was the most frequent death immediate cause), 82.5% of the corpses showed atherosclerotic disease in the ascending aorta. The fat deposition was observed in the left ventricle in 95% of heart samples and was associated with alcoholism (Fisher test 0.04, odds ratio [OR] 0.161 [95% CI 0.072 to 0.36]; p <0.05) ; smoking (Fisher Test 0.508; OR 0581 [95% CI 0.431 to 0.73]; p <0.05), presence of Frank's sign (Fisher Test 0.502; OR 0.567 [95% CI 0.414 to 0.775]; p <0.05); atherosclerosis of the ascending aorta (0.774 OR [95% CI 0.6405 to 0.936]; p <0.05); acute myocardial infarction (OR 0.730 [95% CI 0.600 to 0.888]; p <0.05) and macroscopic finding of cardiac hypertrophy (OR 0.700 [95% CI 0.525 to 0.933]; p <0.05). It was observed that the epicardial fat and pericoronary adipose tissue are the most frequent topographies in fat accumulation in the left heart chamber and the epicardial fat deposition are associated with myocardial adiposity (Fisher test 0.019; 0.097 OR [95% CI 0.033 to 0.284 ]; p <0.05). Fat deposition in the cardiac left ventricle related with the thickness of the abdominal fat cushion. We conclude that the fat deposition in the left ventricle is common and is associated with cardiovascular disease risk factors. It is evident that cardiac adiposity can not be considered a random autopsy finding, requiring diagnostic research and more studies to investigate the clinical implications.

O uso crônico de altas doses de glicocorticoides (GC) aumenta tecidos adiposos (TA) centrais. Essa pesquisa visou verificar os efeitos do uso contínuo de GC em doses mais baixas sobre diferentes TAs. Ratos Wistar machos com 10 semanas de vida foram divididos em 2 grupos: controle (CON) e cortisol (CORT) e foram implantados com minibomba osmótica, pela qual o grupo CORT recebeu 0,6 mg/kg/d de cortisol e o grupo CON recebeu salina, por 6 semanas. Os resultados mostram um aumento da gordura subcutânea (SC) abdominal dos animais CORT, acompanhada de: aumento da atividade máxima das enzimas ATP-citrato-liase e glicose-6-fosfato desidrogenase; redução da expressão da enzima AMPK; aumento da expressão da enzima 11&#946;HSD1 e das triglicérides circulantes. Esses dados sugerem que a intervenção aumentou a SC abdominal devido maior atividade de enzimas lipogênicas e de um possível aumento da captação de lipídeos séricos por esse tecido, o que pode ter resultado do aumento da concentração local de GC provocado pela expressão aumentada da 11&#946;HSD1. / Chronic use of high doses of glucocorticoids (GC) increases central adipose tissue (AT). This research aimed to verify the effects of continuous use of lower doses of GC on different TAs. Male Wistar rats, 10 weeks old, were divided into 2 groups: control (CON) and Cortisol (CORT), and were implanted with osmotic minipump, whereby CORT group received 0.6 mg/kg/d of cortisol and CON group received saline, for 6 weeks. The results show an increase in abdominal subcutaneous fat (SC) of CORT animals accompanied by: increased maximum activity of ATP citrate lyase and glucose 6-phosphate dehydrogenase enzymes; reduced expression of AMPK enzyme; increased expression of 11&#946;HSD1 enzyme and circulating triglycerides. These data suggest that the intervention increased abdominal SC due to increased activity of lipogenic enzymes and a possible increase in the uptake of serum lipids through this tissue, which may have resulted from increased local GC concentration caused by increased expression of 11&#946;HSD1.

Background: Maternal obesity pre-programme offspring to develop obesity and associated cardiovascular disease later in life. In health, perivascular adipose tissue (PVAT) reduces vascular contractility, an effect lost in obesity and during pregnancy. However, neither the effect of obesity during pregnancy on PVAT function in the mothers nor the possible epigenetic effect in the offspring is known. This study sought to identify detrimental vascular changes in post-partum dams and their offspring resulting from maternal obesity. Methods: Six-eight week old female Sprague-Dawley rats were fed a 10% fat (control) or 45% fat diet (HFD) for 12 weeks before mating, throughout pregnancy and during lactation. Offspring received the control diet until sacrifice at 12 (12wo) or 24 (24wo) weeks of age. PVAT-denuded (with or without exogenous PVAT) and PVAT-intact mesenteric arteries from mothers and pups were mounted on a wire myograph and vascular contractility to thromboxane A2 agonist (U46619) and norepinephrine was assessed in the presence of pharmacological tools. Western blotting, immunoprecipitation and an AMPK activity assay were used to detect any changes in the PVAT environment. Results: Offspring of obese mothers were overweight, mildly hypertensive and insulin resistant. Contractions in PVAT-denuded arteries from HFD dams and their offspring were reduced by a mechanism involving increased protein O-GlcNAcylation. PVAT exerted an anti-contractile effect in vessels from control offspring and their mothers through the release of relaxant factors, which included nitric oxide (NO). The anti-contractile effect of PVAT was lost in HFD offspring due to reduced NO bioavailability and increased O-GlcNAcylation, which lead to decreased AMPK activity within PVAT. However, simultaneous AMPK activation within PVAT partially restored the anti-contractile capability in HFD offspring. Reduced NO bioavailability also lead to PVAT dysfunction in HFD mothers. Conclusions: Elevated insulin levels in the HFD offspring may lead to enhanced glucose uptake and increased protein O-GlcNAcylation, which contributes to the PVAT dysfunction in HFD offspring. The PVAT dysfunction, which is associated with reduced NO bioavailability in HFD mothers and their offspring may be the result of reduced AMPK phosphorylation of nitric oxide synthase within PVAT.

Philosophiae Doctor - PhD / Obesity is a complex metabolic disease of excessive fat accumulation. It is a worldwide epidemic affecting billions of people and its pharmacological management is hampered by drug toxicity and undesirable side effects. Therefore, a need still exists for the development of safe medication for treatment of obesity. Nanotechnology involves the use of small particles at atomic and molecular scale. It has application in medical diagnostics, drug delivery and molecular imaging. Various nanoparticles (NPs) functionalized with different biomolecules have been successfully used in many therapeutic and research applications due to their versatility, ease of chemical synthesis, low toxicity and unique properties. Examples of NPs used in this study are Gold nanoparticles (GNPs) and Quantum dots (QDs). GNPs and QDs are extensively used as drug delivery, labelling and imaging tools in biomedical research. Nanotechnology offers a new potential useful avenue for solving the problem of toxicity of anti-obesity drugs. This could be achieved through targeted drug delivery. In this study, rats were fed a high fed diet (HFD) to induce obesity. The streptavidin conjugated GNPs and QDs were functionalized with biotinylated adipose-homingpeptide (AHP) and/or anti-obesity drug (Gallic acid). Functionalization was characterized using agarose gel electrophoresis, UV-vis spectroscopy and transmission electron microscopy. The binding-specificity and targeting ability of AHP was evaluated in vitro and in vivo. The apoptotic effect of AHP functionalized-drug loaded GNPs (AHP-GA-GNPs) was tested in vitro using APOPercentage TM and Caspase-3 activation assays. The in vitro data indicated that the binding was specific to prohibitin (PHB) expressing cells (MCF-7 and Caco-2), and that the binding was temperature dependent. PHB was confirmed as a target for AHP after overlaying AHP-FITC and anti-prohibitin antibody staining. Cellular uptake was detected on the cells treated with AHP-functionalized NPs as compared to unfunctionalized NPs. The GA and AHP-GA-GNPs reduced cellular viability and induced apoptosis through activation of Caspase-3. The Ex-vivo studies using primary endothelial cells (ECs) isolated from the WAT of lean and obese Wistar rats showed that the binding of AHP was receptor mediated, and specific to receptors differentially expressed in ECs from obese WAT. The in vivo studies showed that, treatment of obese rats with AHP-functionalized NPs resulted in targeted delivery of the NPs to the WAT as compared to those treated with unfunctionalized NPs. Qualitative analysis using fluorescence microscopy and IVIS Luminar XR, live-imaging system showed that the unfunctionalized NPs accumulated mostly in the organs of the reticuloendothelial system, namely: liver, spleen, lungs and kidneys. In contrast, AHP-functionalized NPs accumulated mostly in the WATs as compared to the rest of the organs of the obese rats. Uptake and binding of the NPs to the tissues was quantitatively confirmed by the inductive coupled plasma-optical emission spectroscopy (ICP-OES). In conclusion, this study reports the 1) successful functionalization of GNPs and QDs with AHP, 2) use of AHP-functionalized GNPs and QDs as delivery and imaging agents to the WAT, and 3) potential use of AHP-functionalized drug-loaded GNPs in the treatment of obesity.

It has been shown that post-menarcheal girls are more likely to have increased their body weight and body mass index (BMI) than pre-menarcheal girls of the same age. In addition to the metabolic changes which occur during this interval, behavioural risk factors synergize to promote weight gain, putting adolescents at a much higher risk for excess weight gain and its associated health complications. Moreover, obesity during adolescence increase the risk of becoming an obese adult. A systematic review of English and French articles using MEDLINE, EMBASE, Cochrane, and CINAHL was conducted. Studies underwent a three level screening assessment by two independent assessors. Only studies with post-menarcheal weight change information were selected for data extraction and quality assessment, which was conducted by two independent reviewers. A meta-analysis was conducted for weight change and included 389 girls. Five studies discussed the effects of menarche on body weight change. Pooled results for three studies indicated a 10.39 kg increase from pre to post-menarche (95% CI, 9.16-11.62). The other two studies showed significant increases in body fat mass (p<0.05) and higher skinfolds measurements for post-menarcheal girls compared to pre-menarcheal girls. It is important to further explore the bio-psychosocial and environmental factors influencing the weight, especially the total fat mass and body fat distributions in young adolescent girls during the menarche transition in order to develop and evaluate preventive intervention strategies to prevent adolescent and adult obesity.

Adipose tissue plays a central role in the regulation of lipid storage and mobilization. A tight control between adipose tissue lipid storage and mobilization functions must be exerted to prevent an overload of lipids at other organs such as the heart, liver and skeletal muscles, and favor the risk of developing metabolic disorders, such as Type 2 diabetes and cardiovascular diseases (CVD). There is strong evidence from animal studies that low oxygen levels (hypoxia) are noted in adipose tissue as the mass of the organ excessively expands and, in turn, exacerbates some adipose tissue functions. Whether hypoxia exposure, which could be derived from reduced environmental oxygen availability, disease or a combination of both, affects adipose tissue lipid storage and mobilization functions in humans is not well known. Using in vitro and in vivo approaches, this thesis aimed at characterizing the effects of hypoxia on human adipose tissue lipid storage and lipid mobilization functions. Study I investigated how hypoxia can modulate human adipose functions such as lipid storage and lipid mobilization in vitro. Study II examined whether acute intermittent hypoxia, which simulates obstructive sleep apnea, affects adipose tissue lipid storage/mobilization functions and triglyceride levels in healthy young men in postprandial state. Study III tested the effect of an acute 6-hour continuous exposure to hypoxia (fraction of inspired oxygen (FIO2) = 0.12)) on plasma triglyceride levels in healthy young men in the fasting state. Study I indicates that both acute (24h) and chronic (14d) hypoxia (3%, and 10% O2) modulate human adipose tissue lipid storage and mobilization functions in a different manner. Study II demonstrates that acute exposure to intermittent hypoxia (6h) is sufficient to increase plasma non-esterified fatty acids (NEFA) levels, as well as insulin levels, but does not alter circulating triglyceride or subcutaneous adipose tissue lipid storage and/or mobilization capacity ex vivo in healthy men. Study III shows that acute exposure to normobaric hypoxia increases circulating NEFA and glycerol concentrations but did not translate in altering circulating triglycerides in fasting healthy men. In conclusion, our observations suggest that an exposure to reduced oxygen levels impairs human adipose tissue storage and/or mobilization functions, a phenomenon known in the development of metabolic disorders, such as Type 2 diabetes and CVD.

White adipocytes surround almost all blood vessels in the human body. It was thought previously that these cells merely provide mechanical support for the adjacent small vessels and are little more than fat storage units. Recent studies have identified these cells as metabolic and vasoactive engines that produce and secrete molecules that can affect the function of their adjacent small vessels. The adipocytes and a number of other cell types (including inflammatory cells) surrounding the vessels are collectively termed the PeriVascular Adipose Tissue (PVAT). Work from our group has shown previously that, in health, PVAT conveys a vasorelaxant effect on adjacent small arteries and that this effect is not observed in obesity thus the vessels must exist at an elevated level of basal tone. It is plausible that increased basal vessel constriction can explain the elevated blood pressure amongst the obese population and a better understanding of the obesity-induced PVAT damage may lead to clues to a new approach in the treatment of the condition which burdens its sufferers with a greater cardivascular risk profile. In this thesis we have studied individuals with morbid obesity at baseline and six months following surgery and observed that PVAT function following dramatic weight loss restores the PVAT vasorelaxant effect close to that observed in lean patients. Moreover, we have concluded that inflammation plays a significant role in this process and indeed using protocols with antioxidant enzymes we were able to restore the damaged PVAT function at baseline. We have have shown also that in health, PVAT vasorelaxant function is independent of the endothelium, and that obesity-induced PVAT damage and its reversal following weight loss and ex-vivo anti-oxidant treatment are both independent of the endothelium and at least in part due to nitric oxide bioavailability. Finally, we have observed that in sleep apnoea, which often coexists with morbid obesity and hypertension, there is a greater degree of PVAT inflammation.

京都大学 / 0048 / 新制・課程博士 / 博士(人間・環境学) / 甲第21862号 / 人博第891号 / 新制||人||213(附属図書館) / 2018||人博||891(吉田南総合図書館) / 京都大学大学院人間・環境学研究科共生人間学専攻 / (主査)教授 林 達也, 教授 石原 昭彦, 教授 久代 恵介 / 学位規則第4条第1項該当 / Doctor of Human and Environmental Studies / Kyoto University / DGAM