Reparo periimplantar em ratos diabéticos tipo 2, tratados pela combinação da terapia fotodinâmica antimicrobiana e compostos polifenóis: caracterização biomecânica, histométrica, microtomográfica e molecular / Periimplant bone repair in type 2 diabetics rats treated with the combination of antimicrobial photodynamic therapy and polyphenol compounds: biomechanical, histometric, microtomographic and molecular characterization

Caracterizar as respostas reparacionais do tecido ósseo após a instalação de implantes em ratos diabéticos tipo 2 tratados sistemicamente com resveratrol e com o uso local da aPDT, por meio das análises biomecânica e molecular. Foram utilizados 128 ratos divididos em quatro grandes grupos: 1- NG: ratos normoglicêmicos; 2- NGrvt: ratos normoglicêmicos tratados com resveratrol oral; 3- T2D: ratos diabéticos tipo 2; e 4- T2Drvt: ratos diabéticos tipo 2 tratados com resveratrol oral. Dentro de cada grupo existem quatro subgrupos: ST- Sem terapia local (n=8), a loja cirúrgica não recebeu terapia local adicional; AM- Azul de metileno (n=8), aplicação tópica de azul de metileno por 60 segundos; FBM- fotobiomodulação (n=8), irradiação com laser em baixa intensidade por 60 segundos; aPDT- Terapia fotodinâmica antimicrobiana (n=8), associação da aplicação de azul de metileno com irradiação com laser em baixa intensidade. A indução do T2D foi feita pela associação de dieta de cafeteria com uma única aplicação de Estreptozotocina (35mg.kg). Após a comprovação do diabetes tipo 2, foi dado início ao tratamento com resveratrol e passadas duas semanas os animais foram submetidos à cirurgia de exodontia dos primeiros molares superiores e instalação dos implantes. Neste momento foram realizadas as terapias locais de acordo com os grupos. Passados 28 dias, foi realizada a eutanasiados animais e realizadas as análises biomecânica (torque de remoção) e molecular de RT-PCR (IBSP, OCN, TRAP OPG e RANK-L). Os dados quantitativos foram submetidos ao teste de normalidade Shapiro Wilk para confirmar a distribuição normal das amostras. Na sequência, foram aplicados os testes de ANOVA um fator ou dois fatores, seguidos de pós teste de Tukey, com nível de significância de 5%. Os resultados da análise biomecânica revelaram que em animais normoglicêmicos tratados ou não por resveratrol tiveram uma diminuição do torque de remoção dos implantes quando empregado o uso de terapias locais. A presença da interferência sistêmica e o uso de terapias locais auxiliaram no aumento nos valores de contra-torque, especialmente no grupo T2Drvt com o uso da aPDT. A análise molecular de RT-PCT aos 28 dias sugere que no grupo NG a expressão de IBSP foi semelhante com a presença ou não das terapias locais, entretanto houve uma diminuição dos genes de OCN e um aumento de TRAP com o uso das terapias. Em NGrvt, houve um aumento na expressão de IBSP na ausência de terapias locais, uma diminuição de OCN e TRAP quando utilizadas as terapias e um aumento expressivo de OPG com ausência de RANK-L com o uso sistêmico de resveratrol sem tratamentos locais. O grupo T2D expressou um aumento de IBSP com o uso da terapia de FBM e a terapia com aPDT elevou a expressão de OCN e diminuiu TRAP e RANK-L. O uso de resveratrol em T2Drvt e sua associação com a aPDT aumentaram a expressão de IBSP e OCN, e além disso diminuíram a expressão de TRAP e RANK-L. A análise conjunta dos resultados permite-nos concluir que o uso sistêmico de resveratrol e a sua associação com a aPDT promoveram uma melhora no reparo periimplantar de ratos diabéticos tipo 2, aumentando a expressão de genes relacionados a mineralização da matriz óssea e diminuindo a expressão de genes relacionados a reabsorção óssea que resultaram em uma melhora da biomecânica óssea(AU)

The aim of this study is to characterize bone tissue repair responses after the installation of implants in type 2 diabetic rats treated systemically with resveratrol and with local use of aPDT, through biomechanical and molecular analysis. One hundred and twenty-eight rats were used, divided into four groups: 1- NG: normoglycemic rats; 2- NGrvt: normoglycemic rats treated with oral resveratrol; 3- T2D: type 2 diabetic rats; and 4- T2Drvt: type 2 diabetic rats treated with oral resveratrol. Within each group, are four subgroups: ST- No local therapy (n=8), the surgical store received no additional local therapy; MB- Methylene blue (n=8), topical application of methylene blue for 60 seconds; FBM- Photobiomodulation (n=8), low intensity laser irradiation for 60 seconds; aPDT- Antimicrobial photodynamic therapy (n=8), association of methylene blue application with low intensity laser irradiation. T2D induction was made by the association of cafeteria diet with a single application of Streptozotocin (35mg.kg). After type 2 diabetes confirmation, resveratrol treatment was started and after two weeks the animals were submitted to upper first molars extraction and implants installation. At this moment the local therapies were performed according to the groups. After 28 days, the animals were euthanized and the biomechanical (removal torque) and molecular analysis of RT-PCR (IBSP, OCN, TRAP OPG and RANK-L) were performed. The quantitative data were submitted to the Shapiro Wilk normality test to confirm the normal distribution of the samples. In the sequence, the ANOVA tests were applied one or two factors, followed by Tukey's post-test, with a significance level of 5%. The results of biomechanical analysis showed that in normoglycemic animals treated or not by resveratrol had a decrease in the implants removal torque when local therapies were applied. The presence of systemic interference and the use of local therapies helped to increase biomechanical values, especially in the T2Drvt group with the use of aPDT. The molecular analysis of RT-PCT at 28 days suggests that in the NG group the expression of IBSP was similar with the presence or not of local therapies, however there was a decrease in OCN genes and an increase in TRAP with the use of therapies. In NGrvt, there was an increase in IBSP expression in the absence of local therapies, a decrease in OCN and TRAP when using therapies and a significant increase in OPG without RANK-L with the systemic use of resveratrol without local treatments. T2D group expressed an increase of IBSP with the use of PBM therapy, aPDT raised the expression of OCN and decreased TRAP and RANKL. The use of resveratrol on T2Drvt and its association with aPDT increased the expression of IBSP and OCN, and also decreased TRAP and RANK-L expression. The overall analysis of the results allows us to conclude that the systemic use of resveratrol and its association with aPDT promoted an improvement in periimplant repair of type 2 diabetic rats, increasing the expression of genes related to bone matrix mineralization and decreasing the expression of genes related to bone resorption that resulted in an improvement of bone biomechanics(AU)

Bloqueio de Receptores AT1 Melhora o Desempenho Funcional Miocárdico na Obesidade / AT1Receptor Blockade Improves Myocardial Functional Performance in Obesity

Resumo Fundamento A obesidade tem sido associada com ativação crônica do sistema renina-angiotensina-aldosterona e importantes alterações no desempenho cardíaco. Objetivo Avaliar a influência do bloqueio de receptores de angiotensina-II do tipo 1 (AT1) sobre a morfologia e desempenho cardíaco de ratos obesos por dieta Métodos Ratos Wistar (n=48) foram submetidos a dieta controle (2,9 kcal/g) ou hiperlipídica (3,6 kcal/g) durante 20 semanas. Após a 16ª semana, foram distribuídos em quatro grupos: Controle (CO), Obeso (OB), Controle Losartan (CL) e Obeso Losartan (OL). CL e OL receberam losartan (30 mg/kg/dia) na água durante quatro semanas. Posteriormente, foram analisadas composição corporal, pressão arterial sistólica (PAS) e ecocardiograma. A função de músculos papilares foi avaliada em situação basal com concentração de cálcio ([Ca2+]o) de 2,50 mM e após manobras inotrópicas: potencial pós-pausa (PPP), elevação da [Ca2+]o e durante estimulação beta-adrenérgica com isoproterenol. A análise dos resultados foi feita por meio de Two-Way ANOVA e teste de comparações apropriado. O nível de significância considerado foi de 5%. Resultados Embora a alteração da PAS não tenha se mantido ao final do experimento, a obesidade se associou com hipertrofia cardíaca e maior velocidade de encurtamento da parede posterior do ventrículo esquerdo.No estudo de músculos papilares em condição basal, CL mostrou menor velocidade máxima de variação negativa da tensão desenvolvida (-dT/dt) do que CO. O PPP de 60s promoveu menor -dT/dt e pico de tensão desenvolvida (TD) em OB e CL, comparados ao CO, e maior variação relativa de TD e velocidade máxima de variação positiva (+dT/dt) no OL em relação a CL e OB. Sob 1,5, 2,0 e 2,5mM de [Ca2+]o, o grupo OL exibiu maior -dT/dt do que CL. Conclusão Losartan melhora a função miocárdica de ratos com obesidade induzida por dieta. (Arq Bras Cardiol. 2020; 115(1):17-28)

Abstract Background Obesity has been associated with chronic activation of the renin-angiotensin-aldosterone system and with significant changes in cardiac performance. Objective To assess the impact of a blockade of angiotensin-II receptor type 1 (AT1receptor) on morphology and on myocardial functional performance in rats with high-fat diet- induced obesity. Methods Wistar rats (n=48) were submitted to control (2.9 kcal/g) or high-fat (3.6 kcal/g) diet for 20 weeks. After the 16thweek they were divided into four groups: Control (CO), Obese (OB), Control Losartan (CL) and Obese Losartan (OL). CL and OL received losartan (30 mg/kg/day) in drinking water for four weeks. Subsequently, body composition, systolic blood pressure (SBP) and echocardiographic variables were analyzed. Papillary muscle function was assessed at baseline with 2.50 mM calcium concentration ([Ca2+]o) and after inotropic maneuvers: post-pause potentiation (PPP), [Ca2+]oelevation, and during beta-adrenergic stimulation with isoproterenol. Analysis of the results was performed by the Two-Way ANOVA and by the appropriate comparison test. The level of significance was set at 5%. Results Although SBP change had been not maintained at the end of the experiment, obesity was associated with cardiac hypertrophy and with increased left ventricle posterior wall shortening velocity. In the study of papillary muscles in basal condition, CL showed lower developed tension maximum negative variation velocity (-dT/dt) than CO. The 60s PPP promoted lower -dT/dt and maximum developed tension (DT) in OB and CL compared with CO, and higher relative DT variation and maximum positive variation velocity (+dT/dt) in OL compared with CL and OB. Under 1.5, 2.0, and 2.5mM [Ca2+]o, the OL group showed higher -dT/dt than CL. Conclusion Losartan improves myocardial function in high-fat diet-induced obesity. (Arq Bras Cardiol. 2020;115(1):17-28)

Establishment of high-fat diet-induced obesity and insulin resistance model in rats / 北京大学学报(医学版)

OBJECTIVE@#To investigate the appropriate conditions and duration for establishing a high-fat diet-induced obesity and insulin resistance model in rats.@*METHODS@#Forty-five 6-week-old male Sprague-Dawley (SD) rats were randomly assigned into 2 groups: (1) control group (CON), (2) high-fat diet group (HFD). HFD was fed with a high-fat diet (45% kcal from fat) while CON with chow diet. After four-weeks of high-fat diet feeding, the rats of obesity resistance (OR) were eliminated according to body weight sorting, whereas obese (OB) rats were continued feeding a high-fat diet until 12 weeks. Body weight and food intake were recorded weekly. Glucose tolerance was evaluated by oral glucose tolerance test (OGTT) in 4 weeks, 8 weeks and 12 weeks. At the end of 12 weeks, insulin releasing test and visceral fat mass were measured and HE staining of the liver, adipose tissue and pancreatic tissue were conducted.@*RESULTS@#After 4 weeks of a high-fat diet, the body weight of HFD was 17.8% higher than that of CON (P=0.001), and the rate of obesity was 67.6%-78.4%. Glucose tolerance of OB rats was impaired with a higher blood glucose concentration at 120 min (P<0.001) and a higher area under the curve (AUC, P=0.037) in OGTT compared with CON. The rate of obesity and insulin-resistance rats was 79.3%. After 8 weeks of feeding, the body weight in OB was 30.4% higher than CON (P<0.001). In OGTT, blood glucose levels at 60 min and 120 min were 35.6% and 36.4% higher than those in CON (both P<0.001), and AUC was 21.7% (P<0.001) higher than that of CON. The rate of obesity and insulin-resistance rats was 100.0%. After 12 weeks of feeding, the body weight in OB was 36.9% higher than that in CON (P<0.001). In OGTT, the blood glucose levels at 60 min and 120 min were 24.8% (P=0.001) and 34.6% (P<0.001) higher than those in CON, and AUC was 16.1% (P=0.019) higher than that of CON. The rate of obesity and insulin-resistance rats was 93.3%. The insulin releasing test showed that serum insulin concentration at each time point (0, 30, 60, 120 min) was higher than that in CON, with a 6.3-times higher than that in CON at 120 min (P=0.008). Pathological changes were observed in islets and liver in the OB rats.@*CONCLUSION@#After 4 weeks of a high-fat diet (45% kcal from fat) feeding in six-weeks SD rats, the rats of OR were eliminated. Impaired glucose tolerance was found in OB rats after 4 weeks of feeding, and the rate was higher after 8-12 weeks of high-fat diet feeding.

Effects of restraint stress and high-fat diet on osseointegration of titanium implants: an experimental study

Abstract This study aimed to investigate the effects of chronic restraint stress (RS) and a high-fat diet (HFD) on the osseointegration of titanium implants in a rat model. After the surgical insertion of titanium implants into the metaphysis of the tibial bone, the rats were randomly divided into four equal groups (n = 8 each): control (CNT), restraint stress (RS), high-fat diet (HFD), and restraint stress plus high fat diet (RS-HFD). CNT: Rats received no further treatment during the 92-day experimental period. RS: Stress was applied to the rats beginning from two days after the implant surgery for one hour per day for the first 30 days, two hours per day for the next 30 days, and three hours per day for the last 30 days. HFD: Rats were fed a HFD for the following 90 days starting two days after surgery. RS-HFD: Rats were fed a HFD and RS was applied to rats for the following 90 days, starting two days after surgery. At the end of the experimental period, the rats were euthanized, and the implants and surrounding bone tissues were removed for histological analysis. Statistical analysis was performed by one way ANOVA and Bonferrroni tests. There were no significant differences in the bone-implant connection levels between the groups (p > 0.05), but in the HFD and RS-HFD groups, the bone filling ratios were found to be lower compared with the controls (p < 0.05) The data analyzed in this study suggest that an HFD with or without chronic RS adversely affected bone tissue in the rats during the 90-day osseointegration period.

Sericin as treatment of obesity: morphophysiological effects in obese mice fed with high-fat diet / Sericina como tratamento da obesidade: efeitos morfofisiológicos de camundongos obesos por dieta hiperlipídica

ABSTRACT Objective To investigate the effects of sericin extracted from silkworm Bombyx mori cocoon on morphophysiological parameters in mice with obesity induced by high-fat diet. Methods Male C57Bl6 mice aged 9 weeks were allocated to one of two groups - Control and Obese, and fed a standard or high-fat diet for 10 weeks, respectively. Mice were then further subdivided into four groups with seven mice each, as follows: Control, Control-Sericin, Obese, and Obese-Sericin. The standard or high fat diet was given for 4 more weeks; sericin (1,000mg/kg body weight) was given orally to mice in the Control-Sericin and Obese-Sericin Groups during this period. Weight gain, food intake, fecal weight, fecal lipid content, gut motility and glucose tolerance were monitored. At the end of experimental period, plasma was collected for biochemical analysis. Samples of white adipose tissue, liver and jejunum were collected and processed for light microscopy analysis; liver fragments were used for lipid content determination. Results Obese mice experienced significantly greater weight gain and fat accumulation and had higher total cholesterol and glucose levels compared to controls. Retroperitoneal and periepididymal adipocyte hypertrophy, development of hepatic steatosis, increased cholesterol and triglyceride levels and morphometric changes in the jejunal wall were observed. Conclusion Physiological changes induced by obesity were not fully reverted by sericin; however, sericin treatment restored jejunal morphometry and increased lipid excretion in feces in obese mice, suggesting potential anti-obesity effects.

RESUMO Objetivo Investigar os efeitos da sericina extraída de casulos de Bombyx mori na morfofisiologia de camundongos com obesidade induzida por dieta hiperlipídica. Métodos Camundongos machos C57Bl6, com 9 semanas de idade, foram distribuídos em Grupos Controle e Obeso, que receberam ração padrão para roedores ou dieta hiperlipídica por 10 semanas, respectivamente. Posteriormente, os animais foram redistribuídos em quatro grupos, com sete animais cada: Controle, Controle-Sericina, Obeso e Obeso-Sericina. Os animais permaneceram recebendo ração padrão ou hiperlipídica por 4 semanas, período no qual a sericina foi administrada oralmente na dose de 1.000mg/kg de massa corporal aos Grupos Controle-Sericina e Obeso-Sericina. Parâmetros fisiológicos, como ganho de peso, consumo alimentar, peso das fezes em análise de lipídios fecais, motilidade intestinal e tolerância à glicose foram monitorados. Ao término do experimento, o plasma foi coletado para dosagens bioquímicas e fragmentos de tecido adiposo branco; fígado e jejuno foram processados para análises histológicas, e amostras hepáticas foram usadas para determinação lipídica. Resultados Camundongos obesos apresentaram ganho de peso e acúmulo de gordura significativamente maior que os controles, aumento do colesterol total e glicemia. Houve hipertrofia dos adipócitos retroperitoneais e periepididimais, instalação de esteatose e aumento do colesterol e triglicerídeos hepáticos, bem como alteração morfométrica da parede jejunal. Conclusão O tratamento com sericina não reverteu todas as alterações fisiológicas promovidas pela obesidade, mas restaurou a morfometria jejunal e aumentou a quantidade de lipídios eliminados nas fezes dos camundongos obesos, apresentando-se como potencial tratamento para a obesidade.

Feed restriction since lactation has reduced anxiety in adult Wistar rats / A restrição alimentar desde a lactação reduziu a ansiedade em ratos Wistar adultos

ABSTRACT Objective To evaluate the effects of macronutrients (protein, carbohydrate and/or lipid) in the diet of young adult (72 days) and adult (182 days) Wistar rats treated ad libitum and with 30% restriction from birth on anxiety in the elevated plus-maze. Methods We used 238 rats treated from birth, composing the groups: Control, Protein, Carbohydrate, Lipid, Carbohydrate and Lipid, Control Restriction, Protein Restriction, Carbohydrate Restriction, Lipid Restriction and Carbohydrate and Lipid Restriction. The animals were weighed at the beginning and at the end of the experiment and tested in the elevated plus-maze. Data were submitted to analysis of variance, followed by the Newman-Keuls Test (p<0.05). Results Among the animals treated ad libitum, the Control, Carbohydrate plus Lipid and Lipid gained more weight than the Carbohydrate and Protein; ad libitum animals gained more weight than those on restriction; among the restrictions, Carbohydrate Restriction rats were the ones that gained less weight. Diet-restricted animals exhibited reduced first-entry latency, greater percentage of entries and time spent, frequency of open arm extremity visits, head dipping (protected and unprotected), and length of stay in the central area of the elevated plus-maze. The animals with 182 days presented greater latency for first entry, reduced frequency of false entries and visits to the ends of the open arms and protected head dipping. Conclusion Food restricted animals, regardless of the macronutrient present in the diet, were less anxious and/or increased their impulsivity and those at 182 days were more anxious and/or with reduced impulsivity.

RESUMO Objetivo Este estudo buscou avaliar os efeitos dos macronutrientes (proteína, carboidrato e/ou lipídeos) na alimentação de ratos Wistar adultos jovens (72 dias) e adultos (182 dias) tratados ad libitum e com restrição a 30% desde o nascimento quanto à ansiedade através do labirinto em cruz elevado. Métodos Foram utilizados 238 ratos tratados desde o nascimento, compondo os grupos Controle, Proteína, Carboidrato, Lipídeos, Carboidrato e Lipídeos, Restrição Controle, Restrição Proteína, Restrição Carboidrato, Restrição Lipídeos e Restrição Carboidrato e Lipídeos. Os animais foram pesados no início e no final do experimento e testados no labirinto em cruz elevado. Os dados foram submetidos à análise de variância, seguida do teste de Newman-Keuls (p<0,05). Resultados Entre os animais tratados ad libitum, os dos grupos Controle, Carboidrato e Lipídeos, e Lipídeos ganharam mais peso do que os Carboidrato e Proteína; os ad libitum ganharam mais peso do que os de restrição; os Restrição Carboidrato foram os que ganharam menos peso. Animais alimentados com restrição de dieta apresentaram menor latência de primeira entrada, maior porcentagem de entradas e de tempo gasto, frequência de visitas às extremidades dos braços abertos, de mergulho (protegido e desprotegido) e tempo de permanência na área central do labirinto em cruz elevado. Os animais com 182 dias demonstraram maior latência para primeira entrada, menor frequência de falsas entradas e visitas às extremidades dos braços abertos e mergulho protegido. Conclusão Os animais em restrição alimentar, independentemente do macronutriente presente na dieta, foram menos ansiosos e/ou mais impulsivos, e os com 182 dias foram mais ansiosos e/ou menos impulsivos.

Effects of restraint stress and high-fat diet on osseointegration of titanium implants: an experimental study

Abstract This study aimed to investigate the effects of chronic restraint stress (RS) and a high-fat diet (HFD) on the osseointegration of titanium implants in a rat model. After the surgical insertion of titanium implants into the metaphysis of the tibial bone, the rats were randomly divided into four equal groups (n = 8 each): control (CNT), restraint stress (RS), high-fat diet (HFD), and restraint stress plus high fat diet (RS-HFD). CNT: Rats received no further treatment during the 92-day experimental period. RS: Stress was applied to the rats beginning from two days after the implant surgery for one hour per day for the first 30 days, two hours per day for the next 30 days, and three hours per day for the last 30 days. HFD: Rats were fed a HFD for the following 90 days starting two days after surgery. RS-HFD: Rats were fed a HFD and RS was applied to rats for the following 90 days, starting two days after surgery. At the end of the experimental period, the rats were euthanized, and the implants and surrounding bone tissues were removed for histological analysis. Statistical analysis was performed by one way ANOVA and Bonferrroni tests. There were no significant differences in the bone-implant connection levels between the groups (p > 0.05), but in the HFD and RS-HFD groups, the bone filling ratios were found to be lower compared with the controls (p < 0.05) The data analyzed in this study suggest that an HFD with or without chronic RS adversely affected bone tissue in the rats during the 90-day osseointegration period.

Resistance Exercise Modulates Oxidative Stress Parameters and TNF-α Content in the Heart of Mice with Diet-Induced Obesity / Exercício Resistido Modula Parâmetros de Estresse Oxidativo e Conteúdo de TNF-α no Coração de Camundongos com Obesidade Induzida por Dieta

Abstract Background: Obesity can be characterized by low-grade chronic inflammation and is associated with an excesso production of reactive oxygen species, factors that contribute to coronary heart disease and other cardiomyopathies. Objective: To verify the effects of resistance exercise training on oxidative stress and inflammatory parameters on mice with obesity induced by a high-fat diet (HFD). Methods: 24 Swiss mice were divided into 4 groups: standard diet (SD), SD + resistance exercise (SD + RE), diet-induced obesity (DIO), DIO + RE. The animals were fed SD or HFD for 26 weeks and performed resistance exercises in the last 8 weeks of the study. The insulin tolerance test (ITT) and body weight monitoring were performed to assess the clinical parameters. Oxidative stress and inflammation parameters were evaluated in the cardiac tissue. Data were expressed by mean and standard deviation (p < 0.05). Results: The DIO group had a significant increase in reactive oxygen species levels and lipid peroxidation with reduction after exercise. Superoxide dismutase and the glutathione system showed no significant changes in DIO animals, with an increase in SD + RE. Only catalase activity decreased with both diet and exercise influence. There was an increase in tumor necrosis factor-alpha (TNF-α) in the DIO group, characterizing a possible inflammatory condition, with a decrease when exposed to resistance training (DIO+RE). Conclusion: The DIO resulted in a redox imbalance in cardiac tissue, but the RE was able to modulate these parameters, as well as to control the increase in TNF-α levels.

Resumo Fundamento: A obesidade pode ser caracterizada por uma inflamação crônica de baixo grau e está associada à produção excessiva de espécies reativas de oxigênio, fatores que contribuem para doenças coronarianas e outras cardiomiopatias. Objetivo: Verificar os efeitos do treinamento resistido sobre os parâmetros de estresse oxidativo e parâmetro inflamatório em camundongos com obesidade induzida por dieta hiperlipídica (DIO). Métodos: 24 camundongos Swiss foram divididos em 4 grupos: dieta padrão (DP), DP + exercício resistido (DP+ER), obesidade induzida por DIO, DIO + ER. Os animais foram alimentados por 26 semanas com DP ou hiperlipídica realizando treinamento resistido nas 8 semanas finais do estudo. Para avaliar parâmetros clínicos foi realizado o teste de tolerância à insulina (TTI) e monitoramento do peso corporal. No tecido cardíaco foram avaliados parâmetros de estresse oxidativo e inflamação. Dados expressos por média e desvio padrão (p < 0,05). Resultados: O grupo DIO teve um aumento significativo nos níveis espécies reativas e peroxidação lipídica com redução após o exercício. A superóxido dismutase e o sistema glutationa não demonstraram alterações importantes nos animais DIO, com elevação perante DP+ER. Somente a atividade da catalase reduziu tanto com influência da dieta como do exercício. Ocorreu um aumento do fator de necrose tumoral-alfa (TNF-α) no grupo DIO, caracterizando um possível quadro inflamatório, com redução quando expostos ao treino resistido (DIO+ER). Conclusão: A DIO ocasionou um desequilíbrio redox no tecido cardíaco, porém o ER foi capaz de modular estes parâmetros, bem como controlar o aumento do TNF-α.

Effects of Isoflavone Supplementation on Lipid Profiles and Antioxidant Enzyme Activities in Growing Rats Fed High Fat Diet

The purpose of this study was to investigate the effects of isoflavone on serum lipids and antioxidant enzymes activities in growing rats fed high lard diet. Twenty four female Sprague-Dawley rats (body weight 50–60 g) were divided into three groups, control, high fat (HF, lard 200 g/kg diet) and high fat + isoflavone (HFI, lard 200 g/kg diet + isoflavone 310.9 mg/kg diet) for 4 weeks. The results of study indicated that body weight gain was not different by isoflavone diet. Mean intake was significantly lower in HF group and HFI group than control group. Food efficiency ratio was significantly higher in HF group and HFI group than control group. The level of serum triglyceride and total cholesterol were significantly lower in HFI group than control group and HF group. The level of high-density lipoprotein cholesterol, was significantly higher in control group than HF group and HFI group. The level of low-density lipoprotein cholesterol was not significantly different by experimental diets, but atherogenic index (AI) was significantly lower in control group and HFI group than HF group. Contents of total cholesterol and triglyceride in liver tissues were found to be insignificant. The concentration of lipid peroxidation, malondialdehyde was significantly lower in control groups and HFI group than HF group. And antioxidant enzymes in liver tissue were not significantly different by lard and isoflavone supplemented diets. In conclusion, it seems possible that isoflavone supplemented high fat diet may produce positive results on level of serum triglyceride, serum total cholesterol, AI and concentration of malondialdyhyde.

Effects of high-fat diet exposure on glucolipid metabolism and ovarian function in offspring of female rats / 中国医师杂志

Objective@#To explore the effects of high-fat diet exposure on glucolipid metabolism and ovarian function in offspring of female Sprague Dawley rats.@*Methods@#Female and male rats were mated in cages at a ratio of 2∶1. Pregnant mice were collected and randomly divided into normal feed group (control group) and high-fat and high-glucose feed group (observation group). Female offspring were selected as the research object. After the offspring entering the stage of sexual maturity, the blood was taken from abdominal aorta artery. The contents of serum related factors were determined by automatic biochemical analyzer and enzyme linked immunosorbent assay (ELISA) kit. Hematoxylin-eosin staining (HE) was used to directly observe the distribution and quantity of liver tissue and the quantity and structure of ovarian follicles.@*Results@#Compared with the normal control group, the body weight, blood glucose, blood lipids and fat coefficient in high-fat diet rats were significantly increased (P<0.05). The secretions of estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH) in the ovary were significantly reduced (P<0.05). HE slices showed that compared with the normal control group, there were fat vacuoles in the cytoplasm of hepatocytes, the increase of hepatocyte arrangement gap, the number of adipocytes and the diameter of fat droplets in the observation group. The quantities of primordial follicles and primary follicles in the ovary showed increasing trend in high-fat diet group, and the diameter of follicles was decreased.@*Conclusions@#High-fat and high glucose diet may cause abnormal glucolipid metabolism. It is speculated that high fat diet may cause ovary to be surrounded by fat through fat accumulation in the abdomen and buttocks of female offspring, which directly leads to dysfunction.

Effects of high-fat diet exposure on glucolipid metabolism and ovarian function in offspring of female rats / 中国医师杂志

Objective To explore the effects of high-fat diet exposure on glucolipid metabolism and ovarian function in offspring of female Sprague Dawley rats.Methods Female and male rats were mated in cages at a ratio of 2∶ 1.Pregnant mice were collected and randomly divided into normal feed group (control group) and high-fat and high-glucose feed group (observation group).Female offspring were selected as the research object.After the offspring entering the stage of sexual maturity,the blood was taken from abdominal aorta artery.The contents of serum related factors were determined by automatic biochemical analyzer and enzyme linked immunosorbent assay (ELISA) kit.Hematoxylin-eosin staining (HE) was used to directly observe the distribution and quantity of liver tissue and the quantity and structure of ovarian follicles.Results Compared with the normal control group,the body weight,blood glucose,blood lipids and fat coefficient in high-fat diet rats were significantly increased (P ＜ 0.05).The secretions of estradiol (E2),follicle stimulating hormone (FSH) and luteinizing hormone (LH) in the ovary were significantly reduced (P ＜ 0.05).HE slices showed that compared with the normal control group,there were fat vacuoles in the cytoplasm of hepatocytes,the increase of hepatocyte arrangement gap,the number of adipocytes and the diameter of fat droplets in the observation group.The quantities of primordial follicles and primary follicles in the ovary showed increasing trend in high-fat diet group,and the diameter of follicles was decreased.Condusions High-fat and high glucose diet may cause abnormal glucolipid metabolism.It is speculated that high fat diet may cause ovary to be surrounded by fat through fat accumulation in the abdomen and buttocks of female offspring,which directly leads to dysfunction.

Preliminary Study on Relationship Between Terminal Ileal Histone Deacetylase 3 Expression and Obesity and Intestinal Flora / 胃肠病学

Background: Histone deacetylase 3 (HDAC3), which is expressed in liver, muscle and adipose tissue, is closely related to fat metabolism. Furthermore, HDAC3 expressed in intestinal epithelial cells is a critical factor that regulates host-commensal flora relationship and maintains intestinal homeostasis. Aims: To investigate the relationship between HDAC3 expression in terminal ileum and obesity and intestinal flora. Methods: Eight SPF C57BL/6 mice and eight germ-free C57BL/6 mice aged six weeks were randomly placed on a standard chow or a high-fat chow, respectively, for 5 weeks. Changes in body weight were recorded weekly, and the terminal ileum was obtained for detection of HDAC3 protein and mRNA expressions by immunohistochemistry and real-time PCR. Results: Increase of body weight of mice in SPF high-fat diet group was much more than that in SPF normal diet group (P0.05). No significant differences were found in HDAC3 protein and mRNA expressions between germ-free high-fat diet group and germ-free normal diet group (P>0.05). Conclusions: Expression of HDAC3 in terminal ileum might be regulated by intestinal flora and participates in the occurrence of obesity.

Impacto metabólico e inflamatorio de una comida rica en grasas saturadas y su relación con la obesidad abdominal / Metabolic and inflammatory postprandial effect of a highly saturated fat meal and its relationship to abdominal obesity

Resumen Introducción. La etapa posprandial se asocia con el incremento de marcadores relacionados con el riesgo cardiovascular, cuya intensidad depende del estado metabólico. Objetivo. Determinar el impacto de la ingestión de una comida rica en grasas saturadas sobre el perfil metabólico e inflamatorio y su relación con la obesidad abdominal. Materiales y métodos. Se hizo un ensayo clínico en 42 individuos (21 con obesidad abdominal). Se midieron, en sangre, la glucosa, la insulina, el perfil lipídico, la proteína C reactiva, los lipopolisacáridos y la interleucina 6, en ayunas y después de la ingestión. Resultados. Además de la obesidad, se registró la presencia de resistencia a la insulina y de niveles elevados de triacilglicéridos y proteína C reactiva en ayunas. Asimismo, se detectaron niveles posprandiales más elevados de glucosa, insulina y triacilglicéridos. La interleucina 6 disminuyó en el grupo de personas sin obesidad y los lipopolisacáridos aumentaron en ambos grupos. Conclusión. La ingestión de una comida rica en grasas saturadas produjo un mayor impacto en las variables glucémicas en el grupo con obesidad y, aunque afectó de forma similar los lípidos en ambos grupos, el incremento de triacilglicéridos fue mayor en presencia de una concentración basal elevada y promovió el aumento de lipopolisacáridos. El estado inflamatorio basal y posprandial afectó en mayor medida al grupo con obesidad. El momento posprandial reflejó el estado más frecuente de los individuos en un día normal y permitió evidenciar la capacidad de respuesta metabólica frente a la ingestión de alimentos, así como los estados tempranos de riesgo metabólico.

Abstract Introduction: The postprandial stage is associated with the increase of markers related to cardiovascular risk, and its intensity depends on the metabolic state. Objective: To determine the impact of a high-fat meal intake on the metabolic and inflammatory profile, and its relationship to abdominal obesity. Materials and methods: This clinical trial included 42 individuals (21 with abdominal obesity). We measured glucose, insulin, lipid profile, reactive C protein, lipopolysaccharides, and interleukin 6 in fasting blood, and four hours after eating. Results: Besides obesity, we found insulin resistance and higher levels of fasting triacylglycerides and C-reactive protein. There were higher postprandial responses to glucose, insulin, and triacylglycerides. Interleukin 6 decreased in the non-obese group, and lipopolysaccharides increased in both groups. Conclusions: A saturated high-fat food intake produced a greater impact on the glycemic variables in the group with obesity, while it affected the lipids in both groups. However, the increase of triacylglycerides was higher in the presence of a high basal concentration, and it promoted the increase of lipopolysaccharides. The basal and postprandial inflammatory state affected the group with obesity more. The postprandial moment reflected the most frequent state of the individuals on a normal day and evidenced the capacity of the metabolic response to food intake, as well as early metabolic risk states.

Influences of high-fat diet during pregnancy on sterol regulatory pathway and hepatic lipid deposition in male rat offspring / 中华围产医学杂志

Objective To analyze the influences of maternal high-fat diet on male rat offspring's blood lipid level and hepatic lipid deposition as well as on the expression of two key factors,sterol regulatory element binding protein-1 (SREBP-1) and SREBP cleavage acting protein (SCAP),involved in hepatic cholesterol regulatory cascade during childhood and adulthood.Methods Pregnant Wistar rats were randomly divided into two groups:high fat diet (HF) group and normal intake control (NC) group (both n=20).Rats in the HF group were fed with high-fat diet till delivery before changing to a normal-fat diet,while the NC group was given the normal-fat diet all through the study.Male offspring born appropriate for gestational age (AGA) in different feeding groups were randomly selected as experimental subjects.Physical development,serum lipid levels and hepatic lipid deposition at the age of 7 and 24 weeks were compared between offspring of the two groups.Expression of SCAP and SREBP-1 at protein level was detected with immunohistochemistry.T test or Chi-square test was used for statistical analysis.Results The average birth weight of HF group was higher than that of NC group [(6.95± 0.25) vs (6.79 ±0.78) g,t=2.088,P=0.038].Large for gestational age (LGA),AGA and small for gestational age (SGA) offspring accounted for 18.6％ (21/113),77.9％ (88/113)and 3.5％ (4/113) in HF group and 7.6％ (10/132),87.9％ (116/132) and 4.5％ (6/132) in NC group (x2=13.500,P=0.001).At the age of 7 weeks,the offspring's body weight in HF group was higher than that in NC group [(68.78±7.55) vs (66.61 ±3.92) g,t=2.303,P=0.023].At the age of 24 weeks,the body weight,body length and abdominal circumference of adult offspring in HF group were significantly higher than those in NC group [(251.74±24.04) vs (216.24±33.42) g,(22.60±0.79) vs (21.59± 1.34) cm,(17.93±0.59) vs (16.83±0.88) cm;t=2.220,2.379,2.927,all P＜0.05].At the age of 7 weeks,offspring's serum total cholesterol (TC) level in HF group was higher than that in NC group [(1.94±0.62) vs (1.23 +0.77) mmol/L,t=2.379,P＜0.05].At the age of 24 weeks,adult offspring's liver index,serum TC,triglyceride (TG),low density lipoprotein-cholesterol (LDL-C) and very low density lipoprotein-cholesterol (VLDL-C) levels were all higher in HF group than in NC group,while the high density lipoprotein-cholesterol (HDL-C) level was lower in HF group [(2.75±0.31)％ vs (2.46±0.39)％,(1.98±0.14) vs (1.45±0.27) mmol/L,(2.96±0.21) vs (2.71 ±0.29) mmol/L,(0.97±0.32) vs (0.71 ±0.21) mmol/L,(0.81 ±0.13) vs (0.52±0.17) mmol/L,(1.74±0.20) vs (1.59±0.29) mmol/L;t=2.264,2.333,2.359,2.088,5.336,1.994,all P＜0.05].Comparative analysis of nonalcoholic fatty liver disease activity scores (NAS) between the two groups showed that the liver lobular inflammation in HF group's offspring was more severe at both 7 and 24 weeks of age (2.29±0.49 vs 1.92±0.45,2.83±0.47 vs 2.22±0.55;t=2.157,3.251,all P＜0.05).At the age of 24 weeks,adult offspring in HF group also showed higher liver steatosis scores (2.81 ± 0.35 vs 2.25 ± 0.30,t=4.609,P＜0.05).Immunohistochemical detection showed that there was no significant difference in SCAP protein expressions in liver tissues of 7-week-old offspring between the two groups (P＞0.05),but higher expression of SREBP-1 protein was observed in HF group than in NC group [(34.16±5.08)％ vs (18.09±3.99)％,t=9.697,P＜0.05].At the age of 24 weeks,the expression levels of both SCAP and SREBP-1 proteins in liver tissues were higher in HF group than in NC group [(31.22±6.01)％ vs (17.98+7.89)％,(61.33± 16.25)％ vs (29.76± 11.21)％;t=2.303,2.274,both P＜0.05].Conclusions High-fat intake during pregnancy can increase offspring's birth weight and the risk for LGA offspring.Maternal high-fat diet even up-regulates the expression of SCAP and SREBP-1 in male offspring born AGA in childhood and this impact become more obvious when reaching adulthood,resulting in excessive increase of body weight,body length and abdominal circumference and elevated serum lipid level and liver lipid deposition.

Podocyte-specific knock-in of PTEN protects kidney against high fat diet / 中华肾脏病杂志

Objective To evaluate the effect of over-expression of phosphatase and tensin homolog does on chromosome ten (PTEN) in podocytes on kidney under high fat diet (HFD) in vivo and clarify the mechanism how PTEN regulates scavenger receptor A (SR-A) expression exposed to oxidized low density lipoprotein (ox-LDL) in podocytes in vitro.Methods The podocyte-specific PTEN knockin (PPKI) mice were fed with HFD to establish mouse model of lipid-induced renal injury.Mice were divided into four groups:ND+Ctrl group,ND+PPKI group,HFD+Ctrl group and HFD+PPKI group.After 24 weeks of dietary intervention,all mice were tested for clinical and biochemical parameters,including serum creatinine (Scr) as well as urine albumin excretion rate (UAER);renal lipid content was measured by oil red O staining and cholesterol quantitative analysis;the pathological changes of glomeruli were observed by PAS staining and electron microscope.Podocyte injury was induced by ox-LDL in vitro.Western blotting was used to detect the changes of SR-A expression induced by ox-LDL after YAP-siRNA interfering (si-YAP),as well as YAP phosphorylation induced by ox-LDL after interfering by PTEN-siRNA (si-PTEN) and PTEN phosphatase inhibitor (Bpv-PTEN),and overexpressing by recombinant adenovirus (ad-PTEN).Results Compared with ND+Ctrl group,HFD+ Ctrl group significantly aggravated the levels of Scr and UAER,the expression of SR-A in podocytes,renal lipid content,mesangial matrix expansion,effacement of podocyte foot processes,and incrassation of glomerular basement membrane (all P ＜ 0.05).Conversely,compared with HFD+Ctrl group,HFD+ PPKI group obviously alleviated the above lipid-induced renal damage (all P ＜ 0.05).In vitro,the expression of SR-A in podocytes was up-regulated when stimulated with ox-LDL (P ＜ 0.05),and the knockout of YAP significantly down-regulated the expression of SR-A induced by ox-LDL (P ＜ 0.05).Exposed to ox-LDL,the expression of p-YAP increased in podocytes (P ＜ 0.05);over-expression of PTEN inhibited p-YAP up-regulation induced by ox-LDL (P ＜ 0.05),while either knockdown of PTEN or inhibition of PTEN phosphatase activity displayed opposite effect (all P ＜ 0.05).Conclusions Over-expression of PTEN in podocytes protected the kidney against damage from HFD in vivo and PTEN might suppress SR-A mediated lipid uptake via dephosphorylating p-YAP to prevent podocyte injury from ox-LDL.

Effectiveness and safety of low-carbohydrate diets

With the recent assertions made by certain Korean media that low-carbohydrate, high-fat diets are panaceas for weight reduction and health improvement, such diets have been in the public spotlight. Medical and nutrition professionals have claimed that the inordinate popularity of low-carbohydrate, high-fat diets may pose a significant threat to public health. The aim of this review was to explore the latest evidence on the effectiveness and safety of low-carbohydrate diets. Recent clinical trials have shown that low-carbohydrate diets result in favorable changes in body weight and biochemical cardiovascular risk factors. However, the safety of low-carbohydrate diets remains inconclusive in the long term. Although the latest guidelines for the management of obesity recommend obese adults to use low-carbohydrate diets as an alternative dietary approach to achieve weight loss depending on each patient's dietary habits and medical status, such diets cannot currently be recommended as a strategy for health promotion among the general population due to long-term safety concerns. The results of cohort studies in Japan that have shown moderate diets lower in carbohydrates to be associated with decreased risks of cardiovascular mortality, total mortality, and type 2 diabetes in Japanese women, suggest that a low-glycemic load diet might be an optimal dietary approach for Korean obese adults with insulin resistance.

Effectiveness and safety of low-carbohydrate diets

With the recent assertions made by certain Korean media that low-carbohydrate, high-fat diets are panaceas for weight reduction and health improvement, such diets have been in the public spotlight. Medical and nutrition professionals have claimed that the inordinate popularity of low-carbohydrate, high-fat diets may pose a significant threat to public health. The aim of this review was to explore the latest evidence on the effectiveness and safety of low-carbohydrate diets. Recent clinical trials have shown that low-carbohydrate diets result in favorable changes in body weight and biochemical cardiovascular risk factors. However, the safety of low-carbohydrate diets remains inconclusive in the long term. Although the latest guidelines for the management of obesity recommend obese adults to use low-carbohydrate diets as an alternative dietary approach to achieve weight loss depending on each patient's dietary habits and medical status, such diets cannot currently be recommended as a strategy for health promotion among the general population due to long-term safety concerns. The results of cohort studies in Japan that have shown moderate diets lower in carbohydrates to be associated with decreased risks of cardiovascular mortality, total mortality, and type 2 diabetes in Japanese women, suggest that a low-glycemic load diet might be an optimal dietary approach for Korean obese adults with insulin resistance.

High Bile Acid-induced by High-fat Diet Impairs Intestinal Mucosa by Down-regulating Stem Cell Function / 胃肠病学

Background:High-fat diet leads to intestinal mucosa barrier dysfunction,but the mechanism is not clear. High-fat diet can induce increase of bile acid. Aims:To investigate whether the high bile acid induced by high-fat diet could act on intestinal stem cell to disrupt stem cell differentiation and imparing the intestinal mucosa. Methods:Twenty-four rats were divided into 3 groups:fed with regular diet,high-fat diet and high-fat diet + cholestyramine,respectively,for 2 weeks. Serum bile acid was detected by ELISA. Ileal diameter was measured and HE staining was performed to observe histology of intestinal mucosa. Expression of Lgr5 gene was determined by RT-qPCR. Ileal tissue fed with regular diet was cultured with deoxycholic acid(DCA)or DCA + cholestyramine for 24 hours in vitro,expression of Lgr5 gene was determined by RT-qPCR. Results:Compared with control group,serum bile acid was significantly increased(P < 0. 05),ileal diameter was significantly decreased,height of intestinal crypts and villus was significantly decreased(P < 0. 05),and expression of Lgr5 gene was significantly decreased in high-fat diet group(P < 0. 01). All the above-mentioned indices were significantly ameliorated in high-fat diet + cholestyramine group(P < 0. 05). In vitro study showed that expression of Lgr5 gene was significantly decreased in DCA group than in control group(P < 0. 01),and cholestyramine could significantly increase expression of Lgr5 gene(P < 0. 05). Conclusions:High-fat diet induced increasing of circulatory bile acid can cause injury of intestinal mucosa by inhibiting stem cell function,which can be ameliorated by cholestyramine.

The Effects of High Fat Diet and Resveratrol on Mitochondrial Activity of Brown Adipocytes

BACKGROUND: Resveratrol (RSV) is a polyphenolic phytoalexin that has many effects on metabolic diseases such as diabetes and obesity. Given the importance of brown adipose tissue (BAT) for energy expenditure, we investigated the effects of RSV on brown adipocytes. METHODS: For the in vitro study, interscapular BAT was isolated from 7-week-old male Sprague Dawley rats. For the in vivo study, 7-week-old male Otsuka Long Evans Tokushima Fatty (OLETF) rats were divided into four groups and treated for 27 weeks with: standard diet (SD); SD+RSV (10 mg/kg body weight, daily); high fat diet (HFD); HFD+RSV. RSV was provided via oral gavage once daily during the in vivo experiments. RESULTS: RSV treatment of primary cultured brown preadipocytes promoted mitochondrial activity, along with over-expression of estrogen receptor α (ER-α). In OLETF rats, both HFD and RSV treatment increased the weight of BAT and the differentiation of BAT. However, only RSV increased the mitochondrial activity and ER-α expression of BAT in the HFD-fed group. Finally, RSV improved the insulin sensitivity of OLETF rats by increasing the mitochondrial activity of BAT, despite having no effects on white adipocytes and muscles in either diet group. CONCLUSION: RSV could improve insulin resistance, which might be associated with mitochondrial activity of brown adipocyte. Further studies evaluating the activity of RSV for both the differentiation and mitochondrial activity of BAT could be helpful in investigating the effects of RSV on metabolic parameters.