Search

Made available in DSpace on 2021-06-25T15:02:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-04-01 Mato Grosso Research Foundation (FAPEMAT), Brazil Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Background. Decreased cardiac contractility has been observed in cirrhosis, but the mechanisms that initiate and maintain cardiac dysfunction are not entirely understood. Aim of the study. We test the hypothesis that cirrhotic cardiomyopathy is related to deterioration of myocardial contractility due to alterations in calcium-handling proteins expression. In addition, we evaluated whether cardiac pro-inflammatory cytokine levels are associated with this process. Methods. Cirrhosis was induced by thioacetamide (TAA, 100 mg/kg/i.p., twice weekly for eight weeks). The myocardial performance was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic challenge. The cardiac calcium handling protein expression was detected by Western blotting. Cardiac TNF-alpha and IL-6 levels were measured by ELISA. Results. Thioacetamide induced liver cirrhosis, which was associated with cirrhotic cardiomyopathy characterized by in vivo left ventricular diastolic and systolic dysfunction as well as cardiac hypertrophy. In vitro baseline myocardial contractility was lower in cirrhosis. Also, myocardial responsiveness to post-rest contraction stimulus was declined. Protein expression for RYR2, SERCA2, NCX, pPBL Ser16 and L-type calcium channel was quantitatively unchanged; however, pPBL Thr17 was significantly lower while IL-6 was higher. Conclusions. Our study demonstrates that cirrhotic cardiomyopathy is associated with decreased cardiac contractility with alteration of phospholamban phosphorylation in association with higher cardiac pro-inflammatory IL-6 levels. These findings provided molecular and functional insights about the effects of liver cirrhosis on cardiac function. (C) 2020 IMSS. Published by Elsevier Inc. Fed Univ Mato Grosso UFMT, Inst Hlth Sci, Ave Alexandre Ferronato 1200, BR-78556267 Sinop, Mato Grosso, Brazil Sao Paulo State Univ, Botucatu Sch Med, Dept Internal Med, Botucatu, SP, Brazil Sao Paulo State Univ, Botucatu Sch Med, Dept Pathol, Botucatu, SP, Brazil Sao Paulo State Univ, Botucatu Sch Med, Dept Internal Med, Botucatu, SP, Brazil Sao Paulo State Univ, Botucatu Sch Med, Dept Pathol, Botucatu, SP, Brazil Mato Grosso Research Foundation (FAPEMAT), Brazil: 161294/2014 CNPq: 442979/2014-2

Made available in DSpace on 2020-12-12T02:14:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Background/Aims: Aortic stenosis-induced chronic pressure overload leads to cardiac dysfunction and congestive heart failure. The pathophysiological mechanisms of the myocardial impairment are multifactorial and include maladaptive β-adrenergic signaling. Exercise training (ET) has been used as a non-pharmacological therapy for heart failure management. The present study tested the hypothesis that exercise training attenuates diastolic dysfunction through β-adrenergic signaling preservation. Methods: Wistar rats were submitted to ascending aortic stenosis (AS) surgery, and after 18 weeks, a moderate aerobic exercise training protocol was performed for ten weeks. Results: ET attenuated diastolic dysfunction, evaluated by echocardiogram and isolated papillary muscle (IPM) assay. Also, ET reduced features of heart failure, cross-sectional cardiomyocyte area, and exercise intolerance, assessed by treadmill exercise testing. The β2 adrenergic receptor protein expression was increased in AS rats independently of exercise. Interestingly, ET restored the protein levels of phosphorylated phospholamban at Serine 16 and preserved the β-adrenergic receptor responsiveness as visualized by the lower myocardial compliance decline and time to 50% tension development and relaxation during β-adrenergic stimulation in the IPM than untrained rats. Additionally, AS rats presented higher levels of TNFα and iNOS, which were attenuated by ET. Conclusion: Moderate ET improves exercise tolerance, reduces heart failure features, and attenuates diastolic dysfunction. In the myocardium, ET decreases the cross-sectional area of the cardiomyocyte and preserves the β-adrenergic responsiveness, which reveals that the adjustments in β-adrenergic signaling contribute to the amelioration of cardiac dysfunction by mild exercise training in aortic stenosis rats. Department of Internal Medicine Botucatu Medical School São Paulo State University Department of Biostatistics Institute of Biosciences of Botucatu São Paulo State University Department of Pathology Botucatu Medical School São Paulo State University Institute of Health Science Federal University of Mato Grosso School of Physical Education and Sport University of São Paulo Department of Internal Medicine Botucatu Medical School São Paulo State University (UNESP) Department of Internal Medicine Botucatu Medical School São Paulo State University Department of Biostatistics Institute of Biosciences of Botucatu São Paulo State University Department of Pathology Botucatu Medical School São Paulo State University Department of Internal Medicine Botucatu Medical School São Paulo State University (UNESP) CAPES: 305399/2015-2 CAPES: 442822/2014-6

Made available in DSpace on 2020-12-12T02:02:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Cirrhotic cardiomyopathy is a condition where liver cirrhosis is associated with cardiac dysfunction. Triggers and blockers of cirrhotic cardiomyopathy are poorly understood, which might compromise the prognosis of chronic liver disease patients. We tested whether exercise training would reduce liver damage induced by thioacetamide and prevent liver cirrhosis-associated cardiomyopathy. Wistar rats were divided into three groups: control, thioacetamide (TAA), or TAA plus exercise. Thioacetamide increased liver weight and serum alanine aminotransferase and aspartate aminotransferase levels. Also, TAA treatment was involved with hepatic nodule formation, fibrotic septa, inflammatory infiltration, and hepatocyte necrosis. The exercise group presented with a reduction in liver injury status. We found that liver injury was associated with disordered cardiac hypertrophy as well as diastolic and systolic dysfunction. Exercise training attenuated cirrhosis-associated cardiac remodeling and diastolic dysfunction and prevented systolic impairment. These results provided insights that exercise training can mitigate cirrhotic cardiomyopathy phenotype. [Figure not available: see fulltext.]. Department of Internal Medicine Botucatu School of Medicine São Paulo State University (UNESP), Botucatu Institute of Health Sciences Federal University of Mato Grosso (UFMT), Avenida Alexandre Ferronato, n°1200, Setor Industrial Department of Morphology Institute of Biosciences Sao Paulo State University (UNESP) Department of Internal Medicine Botucatu School of Medicine São Paulo State University (UNESP), Botucatu Department of Morphology Institute of Biosciences Sao Paulo State University (UNESP)

Aims Liver cirrhosis is the main chronic liver disease and is considered a catabolic disease. Cirrhotic patients have a low energy intake and high energy expenditure at rest, leading to metabolic disorders. Malnutrition is associated with complications of cirrhosis and has been shown that a nutritional intervention with increase of energy intake improves the survival of cirrhotic patients. Therefore, our aim was to evaluate the effect of a high sucrose diet in the liver of animals with cirrhosis induced by thioacetamide and investigate the mechanism involved. Main methods Male Wistar rats were divided into three groups: Control; Thioacetamide; and Thioacetamide + high sucrose diet. The thioacetamide was administrated (100 mg kg−1) intraperitoneally and the sucrose was offered in drinking water (300 g L−1). Key findings The administration of thioacetamide was associated with fibrosis and inflammatory infiltrate in the liver and increased levels of transaminases enzymes. The high sucrose diet promoted a reduction of theses parameters in cirrhotic rats. The malnutrition observed in cirrhotic rats was attenuated by the high sucrose diet shown by the improvements in weight loss, subcutaneous fat, and caloric intake. The high sucrose diet also attenuated the oxidative stress present in the liver of animals with thioacetamide-induced cirrhosis. Significance The high sucrose diet had anti-inflammatory and anti-oxidant effects in the liver of animals with thioacetamide-induced cirrhosis. In addition, the high sucrose diet also improved malnutrition and catabolism present in cirrhosis. Thus, a high sucrose diet may be a therapeutic option for cirrhotic patients in a catabolic state.

Aims Obesity is associated with comorbidities such as diabetes and hepatic steatosis. β-Glucans have been described as effective in treating conditions including dyslipidaemia and diabetes. Thus, the objective of this study was to evaluate the effects of botryosphaeran [(1 → 3)(1 → 6)-β-D-glucan] on obesity and its comorbidities, and understand its mechanism of action. Main methods Obesity was induced in adult male Wistar rats by ingestion of a high-fat diet and water with sucrose (300 g/L) for 8 weeks. Control rats received standard diet. After six weeks, treatment commenced with botryosphaeran (12 mg/kg.b.w., via gavage, 15 days), respective controls received water. Rats were divided into 3 groups: control (C), obese (O), and obese + botryosphaeran (OB). In the 8th week, obesity was characterized. Feed-intake, glucose and lipid profiles, glucose tolerance, and concentrations of glycogen and lipids in liver were analyzed. Protein expression was determined by Western blotting. Key findings Obese rats showed significant increases in weight gain and adipose tissue, presented glucose intolerance, dyslipidaemia, and hepatic steatosis. Botryosphaeran significantly reduced feed intake, weight gain, periepididymal and mesenteric fat, and improved glucose tolerance. Botryosphaeran also reduced triglyceride and VLDL, and increased HDL levels. Furthermore, botryosphaeran increased glycogen and reduced total lipids, triglycerides and cholesterol in liver, and increased AMP-activated protein kinase(AMPK) activity and Forkhead transcription factor 3a(FOXO3a) protein expression in adipose tissue. Significance This study demonstrated that botryosphaeran was effective in reducing obesity, hepatic steatosis, dyslipidaemia insulin resistance and glucose intolerance in diet-induced obese rats, and these effects were, at least in part, associated with reduced feed intake, and AMPK and FOXO3a activities.

Liver cirrhosis is associated with a wide range of cardiovascular abnormalities including hyperdynamic circulation and cirrhotic cardiomyopathy. The pathogenic mechanisms of these cardiovascular changes are multifactorial and include vascular dysregulations. Aim The present study tested the hypothesis that the systemic vascular hyporesponsiveness in thioacetamide (TAA)-induced liver injury model is dependent on nitric oxide (NO) and cyclooxygenase (COX) derivatives. Main methods Wistar rats were treated with TAA for eight weeks to induce liver injury. Key findings The maximal contractile response in concentration-effect curves to phenylephrine was decreased in aorta from TAA-treated rats, but no differences were found in aorta without endothelium, suggesting an endothelium-dependent mechanism in decreased contractile response. There was no difference in the contractile response with and without L-NAME (N(ω)-nitro- l -arginine methyl ester) in rats with liver injury, showing that the TAA treatment impairs NO synthesis. Pre-incubation of the aorta with indomethacin, a COX-inhibitor, normalized the reduced contractile response to phenylephrine in arteries from TAA group. Also, COX-2 and iNOS (inducible nitric oxide syntase) protein expression was increased in aorta from TAA group compared to control group. Animals submitted to TAA treatment had a reduction in systolic blood pressure. Our findings demonstrated that liver injury induced by TAA caused a decrease in aortic contractile response by a COX-dependent mechanism but not by NO release. Also, it was demonstrated an inflammatory process in the aorta of TAA-treated rats by increased expression of COX-2 and iNOS. Significance Therefore, there is an essential contribution of COX-2 activation in extra-hepatic vascular dysfunction and inflammation present in cirrhosis induced by TAA.

Background: Different types of high-fat and/or high-energy diets have been used to induce obesity in rodents. However, few studies have reported on the effects observed at the initial stage of obesity induced by high-fat feeding on cardiac functional and structural remodelling. Objective: To characterize the initial moment of obesity and investigate both metabolic and cardiac parameters. In addition, the role of Ca2+ handling in short-term exposure to obesity was verified. Methods: Thirty-day-old male Wistar rats were randomized into two groups (n = 19 each): control (C; standard diet) and high-fat diet (HF, unsaturated high-fat diet). The initial moment of obesity was defined by weekly measurement of body weight (BW) complemented by adiposity index (AI). Cardiac remodelling was assessed by morphological, histological, echocardiographic and papillary muscle analysis. Ca2+ handling proteins were determined by Western Blot. Results: The initial moment of obesity occurred at the 3rd week. Compared with C rats, the HF rats had higher final BW (4%), body fat (20%), AI (14.5%), insulin levels (39.7%), leptin (62.4%) and low-density lipoprotein cholesterol (15.5%) but did not exhibit alterations in systolic blood pressure. Echocardiographic evaluation did not show alterations in cardiac parameters. In the HF group, muscles were observed to increase their +dT/dt (C: 52.6 ± 9.0 g/mm2/s and HF: 68.0 ± 17.0 g/mm2/s; p < 0.05). In addition, there was no changes in the cardiac expression of Ca2+ handling proteins. Conclusion: The initial moment of obesity promotes alterations to hormonal and lipid profiles without cardiac damage or changes in Ca2+ handling. Resumo Fundamentos: Diferentes tipos de dietas hiperlipídicas e/ou hipercalóricas têm sido usados para induzir obesidade em roedores. No entanto, poucos estudos relataram os efeitos da obesidade induzida por dieta hiperlipídica em sua fase inicial sobre a remodelação cardíaca funcional e estrutural. Objetivo: Caracterizar o momento inicial da obesidade e investigar parâmetros metabólicos e cardíacos. Além disso, analisar o papel do trânsito de Ca+2 em curtos períodos de exposição à obesidade. Métodos: Ratos Wistar com idade de 30 dias foram distribuídos aleatoriamente em dois grupos (n = 19 em cada grupo): controle (C, dieta padrão) e dieta hiperlipídica (HL, dieta rica em gordura insaturada). O momento inicial da obesidade foi definido por medidas semanais do peso corporal, complementadas pelo índice de adiposidade (IA). A remodelação cardíaca foi avaliada por análise morfológica, histológica, ecocardiográfica e funcional dos músculos papilares. Proteínas envolvidas no trânsito de Ca2+ foram determinadas por Western Blot. Resultados: O momento inicial da obesidade ocorreu na terceira semana. Em comparação aos ratos C, os animais HL apresentaram maior peso corporal final (4%), gordura corporal (20%), IA (14,5%), níveis de insulina (39,7%), leptina (62,4%) e lipoproteína de baixa densidade (15,5%), mas não apresentaram alterações na pressão sistólica. A avaliação ecocardiográfica não mostrou alterações nos parâmetros cardíacos. No grupo HL, observou-se um aumento no +dT/dt (C: 52,6 ± 9,0 g/mm2/s e HL: 68,0 ± 17,0 g/mm2/s; p < 0,05) muscular. Além disso, não houve alterações na expressão cardíaca de proteínas envolvidas no trânsito de Ca2+. Conclusão: O momento inicial da obesidade promove alterações nos perfis hormonais e lipídicos sem causar danos cardíacos ou mudanças no trânsito de Ca2+.

Obesity has been shown to impair myocardial performance. Nevertheless, the mechanisms underlying the participation of calcium (Ca(2+) ) handling on cardiac dysfunction in obesity models remain unknown. L-type Ca(2+) channels and sarcoplasmic reticulum (SR) Ca(2+) -ATPase (SERCA2a), may contribute to the cardiac dysfunction induced by obesity. The purpose of this study was to investigate whether myocardial dysfunction in obese rats is related to decreased activity and/or expression of L-type Ca(2+) channels and SERCA2a. Male 30-day-old Wistar rats were fed standard (C) and alternately four palatable high-fat diets (Ob) for 15 weeks. Obesity was determined by adiposity index and comorbidities were evaluated. Myocardial function was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic and lusitropic maneuvers. L-type Ca(2+) channels and SERCA2a activity were determined using specific blockers, while changes in the amount of channels were evaluated by Western blot analysis. Phospholamban (PLB) protein expression and the SERCA2a/PLB ratio were also determined. Compared with C rats, the Ob rats had increased body fat, adiposity index and several comorbidities. The Ob muscles developed similar baseline data, but myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca(2+) was compromised. The diltiazem promoted higher inhibition on developed tension in obese rats. In addition, there were no changes in the L-type Ca(2+) channel protein content and SERCA2a behavior (activity and expression). In conclusion, the myocardial dysfunction caused by obesity is related to L-type Ca(2+) channel activity impairment without significant changes in SERCA2a expression and function as well as L-type Ca(2+) protein levels.

Obesity has become a major public health problem, most commonly treated via dietary restriction to promote weight loss. Although leptin and thyroid hormones are involved in the regulation of energy balance, the role of these hormones after the stabilization of weight loss remains unclear. This study was designed to analyze the effect of thyroid hormone on sustained weight loss and leptin gene expression in obese animals after a loss of 5% to 10% of body weight. Thirty-day–old male Wistar rats were separated into 4 groups: control, obese, calorie restriction (CR), and calorie restriction with triiodothyronine administration (CRT). The obese group had increased weight and adiposity, leptin and insulin levels, and leptin gene expression. Dietary restriction in the CR group resulted in decreased body weight and adiposity, diminished leptin, and increased thyroid hormone receptor β expression. The CRT group, submitted to dietary restriction with concomitant administration of a physiologic triiodothyronine dose, had thyroid hormone receptor β expression at levels comparable with those observed in the control group and simultaneously increased leptin expression as compared with that in the CR group, suggesting that thyroid hormone modulates leptin expression under conditions of calorie restriction. Increased leptin expression in the CRT group did not result in increased circulating leptin or a statistically significant reduction in body weight during the treatment period. These data provide impetus for further study, as a longer treatment period may result in increased circulating leptin and, thus, further reduction in body weight during calorie restriction in an obesity model.

Introduction: Obesity is a disease in which inflammation is directly involved and can lead to impaired renal function. Objective: To evaluate the influence of short term exposure to cafeteria diet on kidney tissue inflammation and advanced glycation end products (AGEs) in the rat plasma. Methods: Male Wistar rats (10 weeks of age, weighing 350 g) were assigned to receive commercial chow diet (C; n = 8 animals/group, 5% of energy from fat) or cafeteria diet (CAF-D, n = 8 animals/group: 29% energy fat) and sucrose in drinking water (300 g/L) for 6 weeks. Results: adiposity index at six weeks was higher in CAF-D group compared to C. The same behavior was observed for plasma levels of glucose, triglycerides, leptin, insulin and AGEs. The gene expression of IL-6 and TNF-α in renal tissue was higher in CAF-D group and no significant difference in adipose tissue. There was no increase of these cytokines in plasma and kidney or histologically. There was a significant decrease of adiponectin in the CAF-D group. Conclusion: The short exposure CAF-D reflects changes in metabolism, increased plasma levels of AGEs, which may reflect the increased expression of inflammatory cytokines in the kidney.

Aim: To investigate whether lycopene can modulate adiponectin levels and SIRT1 and FoxO1 gene expression in the adipose tissue of diet-induced obese rats. Methods: Male Wistar rats were first fed with hypercaloric diet (HD, n = 12) for 6 weeks, and afterward, these rats were randomly assigned to receive HD ( n = 6) or HD with lycopene-rich tomato oleoresin (equivalent to lycopene 10 mg/kg body weight (BW)/day, HD + L, n = 6) by gavage for additional 6 weeks. Plasma lycopene and adiponectin levels were analyzed by high-performance liquid chromatography and immunoassay, respectively. The messenger RNA (mRNA) expressions of adiponectin, Sirtuin 1 (SIRT1), Forkhead box O 1 (FoxO1), fatty acid translocase/cluster of differentiation 36 (FAT/CD36), and PPARγ in adipose tissues were determined by quantitative polymerase chain reaction. Results: Lycopene was detected in the plasma of rats in HD + L group but not in the HD group. Although both BW and adiposity were not different between the two groups, there was a significant increase in both plasma concentration and mRNA expression of adiponectin in the adipose tissue of the HD + L group. In addition, the lycopene supplementation upregulated mRNA expressions of SIRT1, FoxO1, and FAT/CD36 but downregulated PPARγ in adipose tissue of obese rats. Conclusion: These data suggest that lycopene, in the concentration used, is not toxic and also its health benefits in adipose tissue may play a role against obesity-related complications.

Made available in DSpace on 2015-02-02T12:39:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-10-01Bitstream added on 2015-02-02T13:07:53Z : No. of bitstreams: 1 S0066-782X2014002200009.pdf: 347997 bytes, checksum: 4ef12e938c64c2cde2030bd1e978d534 (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundamento: A obesidade é definida por um acúmulo excessivo do tecido adiposo em relação a massa magra tecidual. Estudos realizados nos últimos anos sugerem que a função cardíaca em animais obesos pode se encontrar preservada, aumentada ou reduzida. Objetivo: Estudar o balanço energético do miocárdio com a hipótese de que o aumento na oxidação de ácidos graxos e redução de glicose levam à disfunção cardíaca na obesidade. Métodos: Ratos Wistar machos com 30 dias de idade foram alimentados com uma dieta padrão ou hipercalórica durante 30 semanas. A função e morfologia cardíacas foram analisadas. Neste trabalho foram estudadas as características gerais e comorbidades associadas com a obesidade. A estrutura cardíaca foi determinada pelo peso do coração e do ventrículo esquerdo (VE). A função do miocárdio foi avaliada pela análise de músculos papilares isolados do VE, na condição basal e depois de manobras inotrópicas e lusitrópicas: rigidez do miocárdio, contração pós-pausa, aumento da concentração extracelular de Ca2+, mudança na frequência de estímulos e inibição da via glicolítica. Resultados: Os ratos obesos tiveram um aumento de tecido adiposo e comorbidades associadas à obesidade em relação aos ratos do grupo controle. A análise funcional após o bloqueio pelo iodoacetato não mostrou diferença na regressão linear da tensão desenvolvida (TD), entretanto, a tensão de repouso (TR) apresentou uma diferença estatística significativa entre o grupo controle e o grupo obeso, mais notadamente na inclinação da curva no grupo C. Conclusão: O desequilíbrio energético na obesidade não promoveu disfunção cardíaca. Pelo contrário, a priorização na utilização de ácidos graxos promoveu uma proteção do músculo cardíaco durante a inibição da glicólise, sugerindo que esta via é menos utilizada pelo músculo cardíaco obeso. Background: Obesity is defined by excessive accumulation of body fat relative to lean tissue. Studies during the last few years indicate that cardiac function in obese animals may be preserved, increased or diminished. Objective: Study the energy balance of the myocardium with the hypothesis that the increase in fatty acid oxidation and reduced glucose leads to cardiac dysfunction in obesity. Methods: 30-day-old male Wistar rats were fed standard and hypercaloric diet for 30 weeks. Cardiac function and morphology were assessed. In this paper was viewed the general characteristics and comorbities associated to obesity. The structure cardiac was determined by weights of the heart and left ventricle (LV). Myocardial function was evaluated by studying isolated papillary muscles from the LV, under the baseline condition and after inotropic and lusitropic maneuvers: myocardial stiffness; postrest contraction; increase in extracellular Ca2+ concentration; change in heart rate and inhibitor of glycolytic pathway. Results: Compared with control group, the obese rats had increased body fat and co-morbities associated with obesity. Functional assessment after blocking iodoacetate shows no difference in the linear regression of DT, however, the RT showed a statistically significant difference in behavior between the control and the obese group, most notable being the slope in group C. Conclusion: The energy imbalance on obesity did not cause cardiac dysfunction. On the contrary, the prioritization of fatty acids utilization provides protection to cardiac muscle during the inhibition of glycolysis, suggesting that this pathway is fewer used by obese cardiac muscle. Universidade Estadual Paulista Faculdade de Medicina de Botucatu Departamento de Clínica Médica Universidade Federal do Espírito Santo Centro de Educação Física e Desportos Departamento de Esportes Universidade Federal do Mato Grosso Instituto de Ciências da Saúde Universidade Federal do Mato Grosso do Sul Escola de Fisioterapia Universidade Estadual Paulista Instituto de Ciências Biológicas Departamento de Bioestatística Universidade Estadual Paulista Faculdade de Medicina de Botucatu Departamento de Clínica Médica Universidade Estadual Paulista Instituto de Ciências Biológicas Departamento de Bioestatística

FUNDAMENTO: A obesidade e um fator de risco para muitas complicacoes medicas; a pesquisa medica demonstrou que as alteracoes hemodinâmicas, morfologicas e funcionais estao correlacionadas com a duracao e gravidade da obesidade. OBJETIVO: O presente estudo determinou a influencia do tempo de exposicao a obesidade induzida por dieta com alto teor de gordura no colagenos tipo I e III miocardico. METODOS: Ratos machos com trinta dias de idade, da raca Wistar, foram distribuidos aleatoriamente em dois grupos: um grupo de controle (C) alimentado com racao padrao e um grupo de ratos obesos (Ob) alternadamente alimentados com uma de quatro dietas palataveis ricas em gordura. Cada dieta foi mudada diariamente, e os ratos foram mantidos em suas respectivas dietas por 15 (C15 e Ob15) e 30 (C30 e Ob30) semanas consecutivas. A obesidade foi determinada pelo indice de adiposidade. RESULTADOS: O grupo Ob15 foi similar ao grupo C15 em relacao a expressao de colageno miocardico tipo I; contudo, a expressao no grupo Ob30 foi menor do que no grupo C30. O tempo de exposicao a obesidade foi associado com uma reducao de colageno do tipo I no grupo Ob30, quando comparado com o Ob15. A obesidade nao afetou a expressao do colageno tipo III. CONCLUSAO: Este estudo mostrou que o tempo de exposicao a obesidade por 30 semanas induzida por uma dieta rica em gordura insaturada causou uma reducao na expressao do colageno miocardico tipo I em ratos obesos. No entanto, nenhum efeito foi observado em relacao a expressao do colageno miocardico tipo III

BACKGROUND: Several authors have shown that deterioration of cardiac function is associated with the degree and duration of obesity. It is necessary to establish the gene expression patterns after prolonged periods of obesity. OBJECTIVE: This study tested the hypothesis that increased duration of exposure to obesity leads to a reduction in the mRNA levels of proteins involved in regulation of myocardial Ca2+ homeostasis. In addition, this study verified whether the decrease in mRNA expression was caused by a reduction in thyroid hormone. METHODS: Thirty-day-old male Wistar rats were distributed in two groups: control (C) and obese (Ob). The C group was fed a standard diet and the Ob was fed with high-fat diets for 15, 30 and 45 weeks. Obesity was defined by adiposity index. The gene expression was assessed by quantitative real-time PCR. RESULTS: The adiposity index was higher in the Ob compared to the C after all periods. While obesity at 15 and 45 weeks resulted in a reduction in mRNA of sarcoplasmic reticulum Ca2+- ATPase (SERCA2a), Na+/Ca2+ exchanger (NCX), and calsequestrin (CSQ), L-type Ca2+ channels, ryanodine receptor, SERCA2a, phospholamban (PLB), NCX, and CSQ expression were increased compared to the C after 30 weeks. There was no significant association between T3 levels and mRNA expression. CONCLUSIONS: Our data indicate that obesity over the short and long periods of time may promote alteration in gene expression of Ca2+ homeostasis regulatory proteins without influence by thyroid hormone.

The present study aimed to investigate the beneficial effects of swim training on the promotion–progression stages of rat liver carcinogenesis. Male Wistar rats were submitted to chemically induced liver carcinogenesis and allocated into 4 major groups, according their dietary regimen (16 weeks) and swim training of 5 days per week (8 weeks): 2 groups were fed low-fat diet (LFD, 6% fat) and trained or not trained and 2 groups were fed high-fat diet (HFD, 21% fat) and trained or not trained. At week 20, the animals were killed and liver samples were processed for histological analyses; immunohistochemical detection of persistent or remodeling preneoplastic lesions (pPNL and rPNL) expressing placental glutathione S-transferase (GST-P) enzyme; or proliferating cell nuclear antigen (PCNA), cleaved caspase-3, and bcl-2 protein levels by Western blotting or malonaldehyde (MDA) and total glutathione detection by HPLC. Overall analysis indicated that swim training reduced the body weight and body fat in both LFD and HFD groups, normalized total cholesterol levels in the HFD group while decreased the MDA levels, increased glutathione levels and both number of GST-P-positive pPNL and hepatocellular adenomas in LFD group. Also, a favorable balance in PCNA, cleaved caspase-3, and bcl-2 levels was detected in the liver from the LFD-trained group in relation to LFD-untrained group. The findings of this study indicate that the swim training protocol as a result of exercise postconditioning may attenuate liver carcinogenesis under an adequate dietary regimen with lowered fat intake.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:26:51Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:31:39Z : No. of bitstreams: 1 2-s2.0-84862333929.pdf: 1588872 bytes, checksum: d84eef3b9c43a00d6f4a6b79900182ab (MD5) Made available in DSpace on 2014-05-27T11:26:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-06-21 Aims. To analyze the influence of hyperthyroidism on the gene expression and serum concentration of leptin, resistin, and adiponectin in obese animals. Main Methods. Male Wistar rats were randomly divided into two groups: control (C)fed with commercial chow ad libitumand obese (OB)fed with a hypercaloric diet. After group characterization, the OB rats continued receiving a hypercaloric diet and were randomized into two groups: obese animals (OB) and obese with 25g triiodothyronine (T3)/100BW (OT). The T3 dose was administered every day for the last 2 weeks of the study. After 30 weeks the animals were euthanized. Samples of blood and adipose tissue were collected for biochemical and hormonal analyses as well as gene expression of leptin, resistin, and adiponectin. Results. T3 treatment was effective, increasing fT3 levels and decreasing fT4 and TSH serum concentration. Administration of T3 promotes weight loss, decreases all fat deposits, and diminishes serum levels of leptin, resistin, and adiponectin by reducing their gene expression. Conclusions. Our results suggest that T3 modulate serum and gene expression levels of leptin, resistin, and adiponectin in experimental model of obesity, providing new insights regarding the relationship between T3 and adipokines in obesity. Copyright © 2012 Renata de Azevedo Melo Luvizotto et al. Department of Internal Medicine Botucatu School of Medicine University of São Paulo State, 18618-000 Botucatu, SP Department of Sports Center of Physical Education and Sports Federal University of Espirito Santo (UFES), 29075-910 Vitória, ES

Background This study compared the influence of fasting/refeeding cycles and food restriction on rat myocardial performance and morphology. Methods Sixty-day-old male Wistar rats were submitted to food ad libitum (C), 50% food restriction (R50), and fasting/refeeding cycles (RF) for 12 weeks. Myocardial function was evaluated under baseline conditions and after progressive increase in calcium and isoproterenol. Myocardium ultrastructure was examined in the papillary muscle. Results Fasting/refeeding cycles maintained rat body weight and left ventricle weight between control and food-restricted rats. Under baseline conditions, the time to peak tension (TPT) was more prolonged in R50 than in RF and C rats. Furthermore, the maximum tension decline rate (−d T /d t ) increased less in R50 than in RF with calcium elevation. While the R50 group showed focal changes in many muscle fibers, such as the disorganization or loss of myofilaments, polymorphic mitochondria with disrupted cristae, and irregular appearance or infolding of the plasma membrane, the RF rats displayed few alterations such as loss or disorganization of myofibrils. Conclusion Food restriction promotes myocardial dysfunction, not observed in RF rats, and higher morphological damage than with fasting/refeeding. The increase in TPT may be attributed possibly to the disorganization and loss of myofibrils; however, the mechanisms responsible for the alteration in −d T /d t in R50 needs to be further clarified.

The mechanisms by which diet-induced obesity cause remodeling and cardiac dysfunction are still unknown. Interstitial collagen and myocardial ultrastructure are important in the development of left ventricular hypertrophy, and are essential to the adaptive and maladaptive changes associated with obesity. Thus, the accumulation of collagen and ultrastructural damage may contribute to cardiac dysfunction in obesity. The purpose of the present study was to investigate cardiac function in a rat model of diet-induced obesity and to test the hypothesis that cardiac dysfunction induced by obesity is related to myocardial collagen deposition and ultrastructural damage. Thirty-day-old male Wistar rats were fed standard (control [C]) and hypercaloric diets (obese [Ob]) for 15 weeks. Cardiac function was evaluated by echocardiogram and isolated left ventricle papillary muscle. Cardiac morphology was assessed by histology and electron microscopy. Compared with C rats, Ob rats had increased body fat, systolic blood pressure and area under the curve for glucose, leptin and insulin plasma concentrations. Echocardiographic indexes indicated that Ob rats had increased left ventricular mass, increased systolic stress and depressed systolic function. Analysis of the isolated papillary muscle was consistent with higher myocardial stiffness in Ob compared with C rats. The Ob rats had an increase in myocardial collagen and marked ultrastructural changes compared with C rats. Obesity promotes pathological cardiac remodeling with systolic dysfunction and an increase in myocardial stiffness, which, in turn, is probably related to afterload elevation and cardiac fibrosis. Obesity also causes damage to myocardial ultrastructure, but its effect on myocardial function needs to be further clarified.