Altered Lipid Metabolism Impairs Skeletal Muscle Force in Young Rats Submitted to a Short-Term High-Fat Diet

Obesity and ensuing disorders are increasingly prevalent in young populations. Prolonged exposure to high-fat diets (HFD) and excessive lipid accumulation were recently suggested to impair skeletal muscle functions in rodents. We aimed to determine the effects of a short-term HFD on skeletal muscle function in young rats. Young male Wistar rats (100–125 g) were fed HFD or a regular chow diet (RCD) for 14 days. Specific force, resistance to fatigue and recovery were tested in extensor digitorum longus (EDL; glycolytic) and soleus (SOL; oxidative) muscles using an ex vivo muscle contractility system. Muscle fiber typing and insulin signaling were analyzed while intramyocellular lipid droplets (LD) were characterized. Expression of key markers of lipid metabolism was also measured. Weight gain was similar for both groups. Specific force was decreased in SOL, but not in EDL of HFD rats. Muscle resistance to fatigue and force recovery were not altered in response to the diets. Similarly, muscle fiber type distribution and insulin signaling were not influenced by HFD. On the other hand, percent area and average size of intramyocellular LDs were significantly increased in the SOL of HFD rats. These effects were consistent with the increased expression of several mediators of lipid metabolism in the SOL muscle. A short-term HFD impairs specific force and alters lipid metabolism in SOL, but not EDL muscles of young rats. This indicates the importance of clarifying the early mechanisms through which lipid metabolism affects skeletal muscle functions in response to obesogenic diets in young populations

Effects of ovariectomy and resistance training on oxidative stress markers in the rat liver

OBJECTIVE: The objective of this study was to assess the effects of resistance training on oxidative stress markers in the livers of ovariectomized rats. METHOD: Adult Sprague-Dawley rats were divided into the following four groups (n = 8 per group): sham-operated sedentary, ovariectomized sedentary, sham-operated resistance training, and ovariectomized resistance training. During the resistance training period, the animals climbed a 1.1-m vertical ladder with weights attached to their tails; the sessions were conducted 3 times per week, with 4-9 climbs and 8-12 dynamic movements per climb. The oxidative stress was assessed by measuring the levels of reduced glutathione and oxidized glutathione, the enzymatic activity of catalase and superoxide dismutase, lipid peroxidation, vitamin E concentrations, and the gene expression of glutathione peroxidase. RESULTS: The results showed significant reductions in the reduced glutathione/oxidized glutathione ratio (4.11±0.65 nmol/g tec), vitamin E concentration (55.36±11.11 nmol/g), and gene expression of glutathione peroxidase (0.49±0.16 arbitrary units) in the livers of ovariectomized rats compared with the livers of unovariectomized animals (5.71±0.71 nmol/g tec, 100.14±10.99 nmol/g, and 1.09±0.54 arbitrary units, respectively). Moreover, resistance training for 10 weeks was not able to reduce the oxidative stress in the livers of ovariectomized rats and induced negative changes in the hepatic anti-oxidative/oxidative balance. CONCLUSION: Our findings indicate that the resistance training program used in this study was not able to attenuate the hepatic oxidative damage caused by ovariectomy and increased the hepatic oxidative stress

O treinamento resistido promove modulações gênica e proteica de sinalizadores do metabilismo glicolítico no fígado de ratas ovariectomizadas

Menopause is associated with higher risks of metabolic changes that may compromise women s life quality. Glicemia is regulated by the liver which is responsible for glucose storage at postprandial and for glucose efflux in a fastened state. The absence or the reduction of stradiol levels cause glucose intolerance and deregulated insulin output in bloodstream, setting of the insulin resistance process (RI). Hepatic glucose regulation is directly related to the accurate control of gene expression which encodes different isoforms of oxidation proteins and glucose input proteins. Studies suggest that Resistance Training (TR) prevents RI on ovariectomized (Ovx) rats liver. However there are few molecular events that support TR. Objective: To investigate the Ovx and TR effects over protein and gene expression of biomarkers associated with insulin signalization and glucose oxidation in rats liver. Methods: Adults Sprague-Dawley were divided into 4 groups (n=6 each group): Sedentary Sham-surgical (Sham-Sed); Sedentary-Ovx (Ovx-Sed); (Sham-Tr) and (Ovx-Tr). Tr protocol included 1.1 m vertical climbing with tied weight to the rats tail. Each session consisted of 4 to 9 climbing and 2 minutes of resting between the exercises. Training was performed 3 times a week during 10 weeks. Gene expression was analysed using real time quantitative PCR and protein assays by Western Blotting technic. Results: GLUT2 gene and protein expression and PGC-1α gene expression increased significantly; and p-Akt Ser473 protein expression decreased in Ovx group. TR promoted a greater increase of PGC-1α gene expression and further repair of GLUT2 gene and protein expression and p-Akt Ser473 protein expression. Conclusions: The results show the ovariectomy promotes overexpression of molecular markers that induced RI. These findings suggest that TR may play an important role on the RI prevention in Ovx animals through gene and protein expression repairment of the glycolytic metabolism signalling molecules.Universidade Federal de Minas GeraisA menopausa está associada ao risco aumentado de diversas alterações metabólicas que podem comprometer a qualidade de vida. A glicemia é regulada pelo fígado o qual é responsável pelo armazenamento de glicose no período pós-prandial e pelo efluxo da glicose no jejum. A ausência ou redução dos níveis de estradiol provocam liberação desregulada de insulina na circulação sanguínea e intolerância à glicose, desencadeando o processo de resistência à insulina (RI). A regulação dos níveis de glicose hepática está diretamente relacionada ao controle preciso da expressão dos genes que codificam as diferentes isoformas de proteínas de oxidação e captação de glicose. O treinamento resistido (TR) pode prevenir a RI no fígado de ratas ovariectomizadas (Ovx). No entanto ainda há poucos eventos moleculares que fundamentam o TR no modelo experimental de menopausa. Objetivo: investigar os efeitos da Ovx e do TR sobre a expressão gênica e proteica de biomarcadores relacionados à sinalização da insulina e oxidação da glicose no fígado de ratas. Métodos: Ratas Sprague Dawley adultas foram divididas em 4 grupos (n = 6 por grupo): sham operado sedentário (Sham-Sed), Ovx sedentário (Ovx-Sed), Sham-Tr e Ovx-Tr. O protocolo TR exigiu dos animais a escalada vertical de 1,1 m com pesos atados as suas caudas. Cada sessão consistiu de 4-9 escaladas, com intervalo de 2 minutos entre as escaladas, realizados 3 vezes por semana durante 10 semanas. A análise da expressão gênica foi realizada por PCR-RT pelo método ΔΔCt e as análises proteicas pela técnica de Western Blotting. Resultados: Aumentou significativamente expressão gênica e proteica de GLUT2 e gênica de PGC-1α, também a diminuição da quantificação proteica de Akt-p(Ser473) no grupo ovariectomizados sedentário. A diminuição da expressão gênica e proteica de GLUT2, o aumento da expressão gênica de PGC-1α e proteica de Akt-p Ser473 nos grupos treinados em relação ao grupo controle e ovariectomizados. Conclusão: Os resultados demonstram que a ovariectomia promove a superexpressão de sinalizadores moleculares que induz a RI e o TR foi capaz de promover a restauração desta sinalização. Estes achados sugerem que o TR exerce efeitos notórios na modulação dos sinalizadores que podem induzir a RI em animais Ovx, por meio da restauração da expressão gênica e proteica das moléculas que sinalizam o metabolismo glicolítico

Effects of resistance training and hormone replacement on hepatic glucose transporter 2 (GLUT2) in ovariectomized rats

Oestrogens withdrawal in rats, through ovariectomy (Ovx), has been repeatedly associated with disturbances in lipid metabolism. Among them, liver fat accumulation is well substantiated. On the other hand, there is few information on how liver fat in Ovx rats may affect glucose metabolism in liver. The purpose of the study was to investigate the effects of Ovx and 12 weeks resistance training (RT) program on gene expression of GLUT2 the main glucose transporter in liver and on PPARy a transcription factor known to target GLUT2 gene expression. RT in rat is an exercise training model that has received little attention but that has been shown to result in metabolic adaptations in Ovx rats as well as in post-menopausal women. Holstman rats were divided into 5 groups: Sham-sedentary (Sed), Sham-resistance trained (RT), Ovx-Sed, Ovx-RT, and Ovx-Sed with hormone replacement (E2). The RT protocol consisted of resistance training sessions held every 72 h for 12 weeks, during which session the animals performed 4 to 9 vertical climbs (1.1 m) with progressive weights (up to 30 g) tied to the tail at 2 min intervals. In addition to liver fat, GLUT2 protein levels and PPARy transcripts were all increased (P < 0.05) in Ovx compared to Sham-Sed animals, suggesting an increase hepatic glucose uptake under oestrogens withdrawal. Resistance training as well as oestrogens replacement in Ovx rats decreased liver fat accumulation as well as GLUT2 and PPARy gene expression to the level of Sham-Sed group. The present results suggest that liver fat accumulation in Ovx rats is accompanied by an increased glucose uptake thus providing substrate for an increased de novo lipogenesis. RT appears to be an appropriate exercise model to circumvent these effects.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)A retirada do estrogênio através da ovariectomia (Ovx) em ratas, tem sido constantemente associado a distúrbios do metabolismo lipídico, dentre eles, o acúmulo de gordura hepático que já é bem documentado. Por outro lado, ainda há pouca informação sobre como o fígado gorduroso pode afetar o metabolismo de glicose hepático. Assim, o objetivo deste estudo foi investigar o efeito da Ovx e 12 semanas de treinamento resistido sobre a expressão gênica e proteica do transportador de glucose 2 (GLUT2), o principal transportador de glicose hepático, e sobre o fator de transcrição PPARy, conhecido por modular a expressão de GLUT2. O treinamento resistido (RT) em ratas é uma categoria de exercícios que recebia pouca atenção, mas tem mostrado resultados positivos sobre as alterações metabólicas de ratas Ovx, bem como em mulheres pós-menopausadas. Quarenta ratas da espécie Holstman foram separadas em 5 grupos: Sham-Sedentário (Sed), Sham treinamento resistido (RT), Ovx-Sed, Ovx-RT, e OVX- reposição hormonal (E2). O protocolo de RT foi constituído por sessões a cada 72 h, durante 12 semanas, o qual os animais realizavam de 4 a 9 escaladas verticais (1,1 m) com pesos progressivos (até 30 g), atados à cauda e com intervalos de 2 min. Além da gordura hepática, os níveis proteicos de GLUT2 e a transcrição de PPARy foram aumentados (P < 0,05) em comparação entre animais Ovx e Sham-SED, sugerindo o aumento da absorção de glucose hepática decorrente a retirada do estrogênio. O treinamento resistido, bem como a reposição do hormônio em ratas Ovx reduziu o acúmulo de gordura no fígado, bem como a expressão de GLUT2 e PPARy para níveis próximos ao do grupo controle Sham-Sed. Os resultados deste estudo sugerem que o acúmulo de gordura no fígado de ratas Ovx é acompanhada por um aumento da captação de glicose proporcionando assim, um aumento da lipogênese de novo. RT parece ser um modelo de exercício apropriado para contornar estes efeitos.FAPESP: 2011/21607-

The effect of exercise training on upregulation of molecular markers of bile acid metabolism in the liver of ovariectomized rats fed a cholesterol-rich diet

BACKGROUND: Small heterodimer partner (SHP) is an important transcriptional factor involved in the regulation of glucose, lipid, and bile acid metabolism in the liver. SHP has been reported to be down-regulated in ovariectomized (Ovx) mice and up-regulated by estrogens suggesting a link between estrogens and SHP. The aim of the present study was to determine the effects of exercise training on SHP and key molecular markers of cholesterol and bile acid homeostasis in Ovx rats under cholesterol feeding. METHODS: Our main experimental group was composed of Ovx rats fed a high-cholesterol diet (Ovx-Chol) that was compared to a group of Ovx rats fed a standard diet (Ovx-SD) and a group of sham operated rats fed the cholesterol diet (Sham-Chol). These three groups of Ovx and sham rats were subdivided into either voluntary wheel running (Tr) or sedentary (Sed) groups for 5 weeks. The mRNA expression of all genes was measured by quantitative real-time polymerase chain reaction. RESULTS: Liver total cholesterol levels were not affected by exercise training in any of the experimental conditions. Cholesterol feeding in both sham and Ovx rats resulted in significantly higher hepatic cholesterol accumulation than in Ovx-SD (P &lt; 0.001). Hepatic low-density lipoprotein-receptor (LDL-R) involved in cholesterol uptake from circulation was not influenced by training. A main effect of training &nbsp;was, however, found for transcripts of SHP and cholesterol 7 alpha-hydroxylase (CYP7A1, P &lt; 0.05). CYP7A1 is the main gene involved in bile acid biosynthesis from cholesterol. CONCLUSION: These results suggest that voluntary wheel running modulates cholesterol metabolism in Ovx animals through up-regulation of SHP and bile acid formation.&nbsp;&nbsp;</p

Altered Lipid Metabolism Impairs Skeletal Muscle Force in Young Rats Submitted to a Short-Term High-Fat Diet

Obesity and ensuing disorders are increasingly prevalent in young populations. Prolonged exposure to high-fat diets (HFD) and excessive lipid accumulation were recently suggested to impair skeletal muscle functions in rodents. We aimed to determine the effects of a short-term HFD on skeletal muscle function in young rats. Young male Wistar rats (100–125 g) were fed HFD or a regular chow diet (RCD) for 14 days. Specific force, resistance to fatigue and recovery were tested in extensor digitorum longus (EDL; glycolytic) and soleus (SOL; oxidative) muscles using an ex vivo muscle contractility system. Muscle fiber typing and insulin signaling were analyzed while intramyocellular lipid droplets (LD) were characterized. Expression of key markers of lipid metabolism was also measured. Weight gain was similar for both groups. Specific force was decreased in SOL, but not in EDL of HFD rats. Muscle resistance to fatigue and force recovery were not altered in response to the diets. Similarly, muscle fiber type distribution and insulin signaling were not influenced by HFD. On the other hand, percent area and average size of intramyocellular LDs were significantly increased in the SOL of HFD rats. These effects were consistent with the increased expression of several mediators of lipid metabolism in the SOL muscle. A short-term HFD impairs specific force and alters lipid metabolism in SOL, but not EDL muscles of young rats. This indicates the importance of clarifying the early mechanisms through which lipid metabolism affects skeletal muscle functions in response to obesogenic diets in young populations.</p

Effects of ovariectomy and resistance training on oxidative stress markers in the rat liver

OBJECTIVE: The objective of this study was to assess the effects of resistance training on oxidative stress markers in the livers of ovariectomized rats. METHOD: Adult Sprague-Dawley rats were divided into the following four groups (n = 8 per group): sham-operated sedentary, ovariectomized sedentary, sham-operated resistance training, and ovariectomized resistance training. During the resistance training period, the animals climbed a 1.1-m vertical ladder with weights attached to their tails; the sessions were conducted 3 times per week, with 4-9 climbs and 8-12 dynamic movements per climb. The oxidative stress was assessed by measuring the levels of reduced glutathione and oxidized glutathione, the enzymatic activity of catalase and superoxide dismutase, lipid peroxidation, vitamin E concentrations, and the gene expression of glutathione peroxidase. RESULTS: The results showed significant reductions in the reduced glutathione/oxidized glutathione ratio (4.11±0.65 nmol/g tec), vitamin E concentration (55.36±11.11 nmol/g), and gene expression of glutathione peroxidase (0.49±0.16 arbitrary units) in the livers of ovariectomized rats compared with the livers of unovariectomized animals (5.71±0.71 nmol/g tec, 100.14±10.99 nmol/g, and 1.09±0.54 arbitrary units, respectively). Moreover, resistance training for 10 weeks was not able to reduce the oxidative stress in the livers of ovariectomized rats and induced negative changes in the hepatic anti-oxidative/oxidative balance. CONCLUSION: Our findings indicate that the resistance training program used in this study was not able to attenuate the hepatic oxidative damage caused by ovariectomy and increased the hepatic oxidative stress

Estudo do comportamento cortisol, gh e insulina apos uma sessao de exercicio resistido agudo

INTRODUÇÃO:Muitos trabalhos têm estudado o comportamento hormonal nos exercício resistido, entretanto poucos relacionam os hormônios cortisol, GH e insulina.OBJETIVO:Estudar os ajustes das concentrações plasmáticas dos hormônios cortisol, GH e insulina em exercícios resistidos de mesma intensidade com relação à massas musculares distintas.MÉTODOS:Dez voluntários, com 20,3 ± 4,2 anos, 74,1 ± 10,2 kg de peso, 177,2 ± 4,6 cm de estatura e 23,8 ± 3,2 kg/m2 de IMC, realizaram uma sessão de leg press (LP) e supino reto (SR) com quatro séries com 10 repetições a 70% 1 RM com três minutos de intervalo. Foram coletadas amostras de sangue para dosagem das concentrações plasmáticas de cortisol, GH e insulina em repouso (Pré) e em 0' (Rec. 0'), 30' (Rec. 30') e 90' (Rec. 90') de recuperação.RESULTADOS:As concentrações plasmáticas de cortisol foram significativamente reduzidas ao final da recuperação em LP (2,20±0,37 ng/dl para 1,33±0,38ng/dl) em relação à pré-dosagem. As concentrações de GH e insulina elevaram-se significativamente durante a recuperação. GH em LP foi significativamente maior em Rec. 0' (2,75±3,29 ng/ml para 9,60±5,32 ng/dl) do que em pré. A insulina elevou-se significativamente em Rec. 30' em LP (14,70±7,92 ulU/ml para 21,66 ± 8,61 ulU/ml) e em SR (6,17 ± 2,99 ulU/ml para 19,70 ± 13,8 ulU/ml) em relação à pré. As concentrações plasmáticas de insulina pré em LP foram significativamente superiores a SR (14,70 ulU/ml e 6,17 ± 2,99 ulU/ml).CONCLUSÃO:O exercício resistido promoveu diferentes ajustes nas concentrações hormonais de cortisol, GH e insulina durante o período de recuperação.INTRODUCCIÓN:Muchos trabajos han estudiado el comportamiento hormonal en el ejercicio de resistencia, sin embargo, pocos se refieren el cortisol, GH y las hormonas insulina.OBJETIVO:Estudiar los ajustes de las concentraciones plasmáticas de las hormonas cortisol, GH e insulina en ejercicios resistidos, de igual intensidad, en relación con las masas musculares diferentes.MÉTODOS:Diez voluntarios, con 20,3 ± 4,2 años, 74,1 ± 10,2 kg de peso, 177,2 ± 4,6 cm de estatura y 23,8 ± 3,2 kg/m2 de IMC, realizaron una sesión de leg press (LP) y supino recto (SR) con cuatro series, de 10 repeticiones a 70% 1 RM, con tres minutos de intervalo. Se recolectaron muestras de sangre para dosificación de las concentraciones plasmáticas de cortisol, GH e insulina en reposo (Pré) y en 0' (Rec. 0'), 30' (Rec. 30') y 90' (Rec. 90') de recuperación.RESULTADOS:Las concentraciones plasmáticas de cortisol se redujeron significativamente al final de la recuperación en LP (2,20±0,37 ng/dl para 1,33±0,38ng/dl) en relación con la predosificación. Las concentraciones de GH e insulina aumentaron significativamente durante la recuperación. GH en LP fue significativamente mayor en Rec. 0' (2,75±3,29 ng/ml para 9,60±5,32 ng/dl) en comparación con la predosificación. La insulina se elevó significativamente en Rec. 30' en LP (14,70±7,92 ulU/ml para 21,66 ± 8,61 ulU/ml) y en SR (6,17 ± 2,99 ulU/ml para 19,70 ± 13,8 ulU/ml) en relación con la predosificación. Las concentraciones plasmáticas de insulina, predosificación, en LP fueron significativamente superiores a SR (14,70 ulU/ml y 6,17 ± 2,99 ulU/ml).CONCLUSIÓN:El ejercicio resistido causó diferentes ajustes en las concentraciones hormonales de cortisol, GH e insulina durante el período de recuperación.INTRODUCTION:Many works have studied the hormonal behavior in resistance exercise, however, few relate the cortisol, GH and insulin hormones.OBJECTIVE:To study the adjustments of plasma concentrations of the cortisol, GH and insulin hormones in resisted exercises of the same relative intensity with different muscle musses.METHODS:Ten volunteers, aged 20.3 ± 4.2 years, weight 74.1 ± 10.2 Kg, 177.2 ± 4.6 cm of stature and 23.8 ± 3.2 Kg/m2 of BMI, underwent a session of leg press (LP) and bench press (BP) with four sets of 10 repetitions at 70% 1 RM with three minutes apart. We collected blood samples to measure plasma concentrations of cortisol, GH and insulin at rest (Pre) and 0' (Rec. 0'), 30' (Rec. 30') and 90' (Rec. 90') of recovery.RESULTS:Plasma concentrations of cortisol decreased significantly at the end of the recovery in LP (2.20 ± 0.37 ng/dl to 1.33 ± 0.38 ng/dl) compared to pre. The GH and insulin concentrations significantly increased during recovery. GH was significantly higher in LP Rec. 0' (2.75 ± 3.29 ng/ml to 9.60 ± 5.32 ng/dl) than in pre. Insulin was significantly elevated in Rec. 30' in LP (14.70 ± 7.92 ulU/ml to 21.66 ± 8.61 ulU/ml) and BP (6.17 ± 2.99 ulU/ml to 19.70 ± 13.8 ulU/ml) for pre. The plasma insulin concentrations pre PL were significantly higher in the BP (14.70 ulU/ml and 6.17 ± 2.99 ulU/ml).CONCLUSION:Resisted exercise promoted different adjustments in hormone concentrations of cortisol, GH and insulin during the recovery period