RESUMO
Obesity is associated with other diseases such as diabetes and cancer. Botryosphaeran, a fungal (1â3)(1â6)-ß-d-glucan, is described to present antimutagenic, hypoglycemic, hypocholesterolemic, and antitumor activities when administered by gavage over 15 days in rats and mice. Thus, the present study aims to analyze the metabolic effects of Botryosphaeran (12 mg/kg body weight/day) treatment over 30 days in obese Wistar male rats. Obesity was induced in the rats by a high-fat/high-sugar diet for 8 weeks. Control rats received a standard diet. On the 5th week, Botryosphaeran treatment commenced. Groups: control, obese, and obese+Botryosphaeran 30 days. In the 8th week, obesity was characterized. Feed intake, glucose and lipid profiles, glucose tolerance, and insulin sensitivity were analyzed. Obese rats showed accumulation of visceral adipose tissue, reduction of muscle mass, glucose intolerance, insulin resistance, hyperglycemia, and dyslipidemia. Botryosphaeran effectively reduced weight gains and the accumulation of retroperitoneal adipose tissue, corrected the levels of glucose, triglycerides, and very low-density lipoprotein-cholestrol, and improved insulin sensitivity. Treatment for 30 days was effective in maintaining the beneficial effects demonstrated by this ß-glucan when administered for 15 days without promoting side effects. Treatment with (1â3)(1â6)-ß- d-glucan presented anti-obesogenic and beneficial metabolic effects in Wistar rats; important for the treatment of obesity and its comorbidities.
Assuntos
Resistência à Insulina , beta-Glucanas , Animais , Glicemia , Dieta Hiperlipídica , Glucanos/farmacologia , Glucose , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Insulina , Lipoproteínas LDL , Masculino , Camundongos , Obesidade/metabolismo , Ratos , Ratos Wistar , Açúcares , Triglicerídeos/metabolismo , beta-Glucanas/farmacologiaRESUMO
AIMS: Obesity is associated with comorbidities such as diabetes and hepatic steatosis. ß-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 [(1â¯ââ¯3)(1â¯ââ¯6)-ß-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 (300â¯g/L) for 8â¯weeks. Control rats received standard diet. After six weeks, treatment commenced with botryosphaeran (12â¯mg/kg.b.w., via gavage, 15â¯days), respective controls received water. Rats were divided into 3 groups: control (C), obese (O), and obeseâ¯+â¯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.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Dislipidemias/prevenção & controle , Fígado Gorduroso/prevenção & controle , Glucanos/farmacologia , Intolerância à Glucose/prevenção & controle , Resistência à Insulina , Obesidade/prevenção & controle , Animais , Glicemia/análise , Dislipidemias/etiologia , Dislipidemias/patologia , Fígado Gorduroso/etiologia , Fígado Gorduroso/patologia , Intolerância à Glucose/etiologia , Intolerância à Glucose/patologia , Masculino , Obesidade/etiologia , Obesidade/patologia , Ratos , Ratos WistarRESUMO
BACKGROUND: Oxidative stress plays a major role in diabetic cardiomyopathy pathogenesis. Anti-oxidant therapy has been investigated in preventing or treating several diabetic complications. However, anti-oxidant action on diabetic-induced cardiac remodeling is not completely clear. This study evaluated the effects of rutin, a flavonoid, on cardiac and myocardial function in diabetic rats. METHODS: Wistar rats were assigned into control (C, n = 14); control-rutin (C-R, n = 14); diabetes mellitus (DM, n = 16); and DM-rutin (DM-R, n = 16) groups. Seven days after inducing diabetes (streptozotocin, 60 mg/kg, i.p.), rutin was injected intraperitoneally once a week (50 mg/kg) for 7 weeks. Echocardiogram was performed and myocardial function assessed in left ventricular (LV) papillary muscles. Serum insulin concentration was measured by ELISA. STATISTICS: One-way ANOVA and Tukey's post hoc test. RESULTS: Glycemia was higher in DM than DM-R and C and in DM-R than C-R. Insulin concentration was lower in diabetic groups than controls (C 2.45 ± 0.67; C-R 2.09 ± 0.52; DM 0.59 ± 0.18; DM-R 0.82 ± 0.21 ng/mL). Echocardiogram showed no differences between C-R and C. DM had increased LV systolic diameter compared to C, and increased left atrium diameter/body weight (BW) ratio and LV mass/BW ratio compared to C and DM-R. Septal wall thickness, LV diastolic diameter/BW ratio, and relative wall thickness were lower in DM-R than DM. Fractional shortening and posterior wall shortening velocity were lower in DM than C and DM-R. In papillary muscle preparation, DM and DM-R presented higher time to peak tension and time from peak tension to 50% relaxation than controls; time to peak tension was lower in DM-R than DM. Under 0.625 and 1.25 mM extracellular calcium concentrations, DM had higher developed tension than C. CONCLUSION: Rutin attenuates cardiac remodeling and left ventricular and myocardial dysfunction caused by streptozotocin-induced diabetes mellitus.
Assuntos
Antioxidantes/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Contração Miocárdica/efeitos dos fármacos , Músculos Papilares/efeitos dos fármacos , Rutina/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Cálcio/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/complicações , Cardiomiopatias Diabéticas/sangue , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/fisiopatologia , Insulina/sangue , Masculino , Músculos Papilares/metabolismo , Músculos Papilares/fisiopatologia , Ratos Wistar , Remodelação Ventricular/efeitos dos fármacosRESUMO
Obesity is characterised by chronic low-grade inflammation, and lycopene has been reported to display anti-inflammatory effects. However, it is not clear whether lycopene supplementation modulates adipokine levels in vivo in obesity. To determine whether lycopene supplementation can regulate adipokine expression in obesity, male Wistar rats were randomly assigned to receive a control diet (C, n 6) ora hyperenergetic diet (DIO, n 12) for 6 weeks. After this period, the DIO animals were randomised into two groups: DIO (n 6) and DIO supplemented with lycopene (DIO + L, n 6). The animals received maize oil (C and DIO) or lycopene (DIO + L, 10 mg/kg body weight(BW) per d) by oral administration for a 6-week period. The animals were then killed by decapitation, and blood samples and epididymal adipose tissue were collected for hormonal determination and gene expression evaluation (IL-6, monocyte chemoattractant protein-1(MCP-1), TNF-α, leptin and resistin). There was no detectable lycopene in the plasma of the C and DIO groups. However, the mean lycopene plasma concentration was 24 nmol in the DIO + L group. Although lycopene supplementation did not affect BW or adiposity, it significantly decreased leptin, resistin and IL-6 gene expression in epididymal adipose tissue and plasma concentrations. Also, it significantly reduced the gene expression of MCP-1 in epididymal adipose tissue. Lycopene affects adipokines by reducing leptin, resistin and plasma IL-6 levels. These data suggest that lycopene may be an effective strategy in reducing inflammation in obesity.
Assuntos
Tecido Adiposo/metabolismo , Carotenoides/uso terapêutico , Inflamação/tratamento farmacológico , Interleucina-6/metabolismo , Leptina/metabolismo , Obesidade/tratamento farmacológico , Resistina/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Carotenoides/sangue , Carotenoides/farmacologia , Suplementos Nutricionais , Ingestão de Energia , Epididimo , Inflamação/etiologia , Inflamação/genética , Inflamação/metabolismo , Interleucina-6/genética , Leptina/genética , Licopeno , Masculino , Obesidade/complicações , Obesidade/genética , Obesidade/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Resistina/genéticaRESUMO
FUNDAMENTO: Vários mecanismos têm sido propostos contribuir para a disfunção cardíaca em modelos de obesidade, tais como alterações nas proteínas do trânsito de cálcio (Ca+2) e nos receptores beta-adrenérgicos. Todavia, o papel desses fatores no desenvolvimento da disfunção miocárdica induzida pela obesidade ainda não está claro. OBJETIVO: Este estudo pretende investigar se a obesidade induzida por um ciclo de dieta hipercalóricas resulta em disfunção cardíaca. Além disso, foi avaliado se essa alteração funcional em ratos obesos está relacionada com o prejuízo do trânsito de Ca+2 e do sistema beta-adrenérgico. MÉTODOS: Ratos Wistar machos, 30 dias de idade, foram alimentados com ração padrão (C) e um ciclo de cinco dietas hipercalóricas (Ob) por 15 semanas. A obesidade foi definida pelo aumento da porcentagem de gordura corporal dos ratos. A função cardíaca foi avaliada mediante análise isolada do músculo papilar do ventrículo esquerdo em condições basais e após manobras inotrópicas e lusitrópicas. RESULTADOS: Em comparação com o grupo controle, os ratos obesos apresentaram aumento da gordura corporal e intolerância a glicose. Os músculos dos ratos obesos desenvolveram valores basais semelhantes; entretanto, as respostas miocárdicas ao potencial pós-pausa e aumento de Ca+2 extracelular foram comprometidas. Não houve alterações na função cardíaca entre os grupos após a estimulação beta-adrenérgica. CONCLUSÃO: A obesidade promove disfunção cardíaca relacionada com alterações no trânsito de Ca+2 intracelular. Esse prejuízo funcional é provavelmente ocasionado pela redução da atividade da bomba de Ca+2 do retículo sarcoplasmático (SERCA2a) via Ca+2 calmodulina-quinase.
BACKGROUND: Several mechanisms have been proposed to contribute to cardiac dysfunction in obesity models, such as alterations in calcium (Ca2+) handling proteins and β-adrenergic receptors. Nevertheless, the role of these factors in the development of myocardial dysfunction induced by obesity is still not clear. OBJECTIVE: The purpose of this study was to investigate whether obesity induced by hypercaloric diets results in cardiac dysfunction. Furthermore, it was evaluated whether this functional abnormality in obese rats is related to abnormal Ca2+ handling and the β-adrenoceptor system. METHODS: Male 30-day-old Wistar rats were fed with standard food (C) and a cycle of five hypercaloric diets (Ob) for 15 weeks. Obesity was defined as increases in body fat percentage in rats. Cardiac function was evaluated by isolated analysis of the left ventricle papillary muscle under basal conditions and after inotropic and lusitropic maneuvers. RESULTS: Compared with the control group, the obese rats had increased body fat and glucose intolerance. The muscles of obese rats developed similar baseline data, but the myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca2+ were compromised. There were no changes in cardiac function between groups after β-adrenergic stimulation. CONCLUSION: Obesity promotes cardiac dysfunction related to changes in intracellular Ca2+ handling. This functional damage is probably caused by reduced cardiac sarcoplasmic reticulum Ca2+ ATPase (SERCA2) activation via Ca2+ calmodulin kinase.
Assuntos
Animais , Masculino , Ratos , Cálcio/metabolismo , Miocárdio/metabolismo , Obesidade/metabolismo , Receptores Adrenérgicos beta/metabolismo , Glicemia/análise , Modelos Animais de Doenças , Ingestão de Energia/fisiologia , Coração/fisiopatologia , Modelos Animais , Obesidade/complicações , Obesidade/fisiopatologia , Ratos WistarRESUMO
BACKGROUND: Several mechanisms have been proposed to contribute to cardiac dysfunction in obesity models, such as alterations in calcium (Ca²âº) handling proteins and ß-adrenergic receptors. Nevertheless, the role of these factors in the development of myocardial dysfunction induced by obesity is still not clear. OBJECTIVE: The purpose of this study was to investigate whether obesity induced by hypercaloric diets results in cardiac dysfunction. Furthermore, it was evaluated whether this functional abnormality in obese rats is related to abnormal Ca²âº handling and the ß-adrenoceptor system. METHODS: Male 30-day-old Wistar rats were fed with standard food (C) and a cycle of five hypercaloric diets (Ob) for 15 weeks. Obesity was defined as increases in body fat percentage in rats. Cardiac function was evaluated by isolated analysis of the left ventricle papillary muscle under basal conditions and after inotropic and lusitropic maneuvers. RESULTS: Compared with the control group, the obese rats had increased body fat and glucose intolerance. The muscles of obese rats developed similar baseline data, but the myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca²âº were compromised. There were no changes in cardiac function between groups after ß-adrenergic stimulation. CONCLUSION: Obesity promotes cardiac dysfunction related to changes in intracellular Ca²âº handling. This functional damage is probably caused by reduced cardiac sarcoplasmic reticulum Ca²âº ATPase (SERCA2) activation via Ca²âº calmodulin kinase.
Assuntos
Cálcio/metabolismo , Miocárdio/metabolismo , Obesidade/metabolismo , Receptores Adrenérgicos beta/metabolismo , Animais , Glicemia/análise , Modelos Animais de Doenças , Ingestão de Energia/fisiologia , Coração/fisiopatologia , Masculino , Modelos Animais , Obesidade/complicações , Obesidade/fisiopatologia , Ratos , Ratos WistarRESUMO
AIMS: Leptin resistance has been associated with cardiac lipotoxicity; however, whether leptin resistance is a risk factor associated with cardiac lipotoxicity at different time points in diet-induced obesity is unclear. The objective of this study was to evaluate this relationship. MAIN METHODS: Male Wistar rats were fed a normal chow diet (12% from fat) or a high-fat diet (49% from fat) for 15 and 45 weeks, respectively. The adiposity index, body weight and co-morbidities were evaluated. Heart lipotoxicity was assessed by analyzing cardiac function and morphological changes as well as cardiac triglyceride, ceramide and lipid hydroperoxide accumulations. Cardiac apoptosis was examined using the TUNEL method. Leptin function was determined by examining plasma leptin levels, cardiac leptin receptors (OB-R) and related phosphorylations of AMP-activated kinase protein (AMPK) and Acetyl CoA carboxylase (ACC). KEY FINDINGS: The diet-induced obesity was characterized by an elevated adiposity index, body weight and leptin levels at both 15 and 45 weeks. There was no difference between groups in the cardiac triglyceride or lipid hydroperoxide levels. Interestingly, ceramide levels decreased in obese animals in both experimental periods. The cardiac morphological and functional parameters were not altered. Although down-regulation of OB-R has occurred in chronic obesity, it did not adversely affect AMPK or ACC phosphorylation. SIGNIFICANCE: The development of obesity via long-term feeding of a high-fat diet to rats does not result in cardiac lipotoxicity but promotes the down-regulation of OB-R. However, this does not result in altered levels of AMPK or ACC phosphorylations in this animal model.
Assuntos
Gorduras na Dieta/toxicidade , Leptina/sangue , Obesidade/fisiopatologia , Receptores para Leptina/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Acetil-CoA Carboxilase/metabolismo , Adiposidade , Animais , Apoptose , Ceramidas/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Marcação In Situ das Extremidades Cortadas , Peróxidos Lipídicos/metabolismo , Masculino , Miocárdio/metabolismo , Fosforilação , Ratos , Ratos Wistar , Receptores para Leptina/genética , Fatores de Risco , Fatores de Tempo , Triglicerídeos/metabolismoRESUMO
BACKGROUND: Obesity is rapidly becoming a worldwide epidemic that affects children and adults. Some studies have shown a relationship between obesity and infertility, but until now it remains controversial. Thus, the aim of the present study was to investigate the effect of high-fat diet-induced obesity on male reproductive parameters. METHODS: In a first experiment, male Wistar rats were fed a high-fat diet (HFD) or standard chow (SD) for 15, 30 or 45 weeks, after which they were evaluated by adiposity index, serum leptin levels, reproductive organ weights and sperm counts. In a second experiment, rats received HFD or SD only for 15 weeks, long enough to cause obesity. Sexual hormones and sexual behavior were evaluated in these animals, as well as fertility after natural mating. Another group of rats was submitted to motility analysis and fertility evaluation after in utero insemination. RESULTS: After 15, 30 or 45 weeks, HFD-fed animals presented significant increases in obesity index and serum leptin levels. Reproductive organ weights and sperm counts in the testis and epididymis were similar between the two groups at all timepoints studied. Sexual behavior was not altered by the diet regimen, and HFD fertility after natural mating was also similar to SD-fed animals. Intergroup testosterone levels were also comparable, but estradiol levels were increased in HFD rats. Furthermore, sperm quality was reduced in HFD animals as evidenced by their decreased percentage of sperm with progressive movement. This altered motility parameter was followed by a trend toward reduction in fertility potential after artificial in utero insemination. CONCLUSIONS: The results reported herein showed that obesity can affect sperm quality, by reducing sperm motility, without affecting other sperm parameters. The low sperm quality caused a slight reduction in fertility potential, showing that obesity may lead to impairment in male fertility.
Assuntos
Gorduras na Dieta/administração & dosagem , Obesidade/fisiopatologia , Motilidade dos Espermatozoides , Animais , Estradiol/sangue , Infertilidade Masculina/etiologia , Leptina/sangue , Masculino , Obesidade/etiologia , Ratos , Ratos Wistar , Comportamento Sexual Animal , Testosterona/sangueRESUMO
BACKGROUND: This study tested whether rats with obesity induced by a hypercaloric diet (HD) present higher nutritional, endocrine, and cardiovascular disturbances compared with counterparts with obesity induced by overfeeding of a standard diet. An additional objective was to compare the isolated influence of HD on these parameters in lean and obese rats. MATERIAL/METHODS: Twenty Wistar-Kyoto rats were distributed into four groups: CD-lean, CD-obese, HD-lean, and HD-obese. CD (control diet) and HD groups received commercial standard chow and HD, respectively, for 20 weeks. The lean and obese groups included obesity-resistant and obesity-prone animals, respectively. Nutritional and metabolic evaluation involved measurement of calorie intake, dietary efficiency, body weight, adiposity, glycemia, triacylglycerol, insulin, and leptin. Cardiovascular evaluation included systolic blood pressure measurement, echocardiography, and analyses of myocardial morphology and myosin heavy-chain composition. RESULTS: In both diets, obesity was characterized by increased adiposity, hyperleptinemia, hypertriacylglycerolemia, hyperinsulinemia, and cardiomyocyte nuclear hypertrophy. HD promoted hyperleptinemia and cardiac remodeling, characterized by nuclear and ventricular hypertrophy, as well as improved systolic performance in both the obesity-prone and obesity-resistant biotypes. In contrast to HD-lean, HD-obese rats presented more accentuated endocrine responses, including hyperglycemia, lower glycemic tolerance, and hyperleptinemia as well as interstitial fibrosis compared with the CD-obese animals. CONCLUSIONS: This study confirmed the primary hypothesis that rats with HD-induced obesity present more accentuated nutritional and endocrine disturbances compared with their counterparts with obesity resulting from overfeeding. In addition, dietary effects were more important between the obese groups, supporting evidence of an interaction between diet and biotype.
Assuntos
Sistema Cardiovascular/metabolismo , Dieta , Sistema Endócrino/metabolismo , Ingestão de Energia/fisiologia , Fenômenos Fisiológicos da Nutrição/fisiologia , Obesidade/metabolismo , Animais , Pressão Sanguínea/fisiologia , Peso Corporal , Carboidratos/análise , Sistema Cardiovascular/diagnóstico por imagem , Suscetibilidade a Doenças , Ácidos Graxos/análise , Masculino , Miócitos Cardíacos/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Ratos , Ratos Wistar , Sístole/fisiologia , UltrassonografiaRESUMO
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 beta expression. The CRT group, submitted to dietary restriction with concomitant administration of a physiologic triiodothyronine dose, had thyroid hormone receptor beta 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.