Exercise training prevents obesity-associated disorders: Role of miRNA-208a and MED13.

Exercise training (ET) has been established as an important treatment for obesity, since it counteracts aberrant cardiac metabolism and weight gain; however, underlying mechanisms remain to be further determined. MicroRNAs (miRNAs) inhibit protein expression by base-pairing with the 3' UTRs of mRNA targets. MiRNA-208a is a cardiac-specific miRNA that regulates ß-MHC content and systemic energy homeostasis via MED13. We investigated whether ET regulates the cardiac miRNA-208a and its target MED13, reducing the weight gain and ß-MHC expression in obese Zucker rats (OZR). OZR (n = 11) and Lean (L, n = 10) male rats were assigned into 4 groups: OZR, trained OZR (OZRT), L and trained L (LT). Swimming ET consisted of 60 min of duration, 1x/day, 5x/week/10 weeks. MiRNA and gene expression were analyzed by real-time PCR and protein levels by western blot. Resting bradycardia was observed in trained groups. ET reduced weight gain, retroperitoneal fat weight and adipocyte cell size in OZRT compared with OZR group. Cardiac miRNA-208a levels increased 57% in OZR paralleled with a decrease of 39% in MED13 protein levels compared with L group. In contrast, ET corrected the cardiac miRNA-208a and MED13 levels in OZRT compared with L group. Furthermore, ET reduced the increased cardiac mass and normalized ß-MHC protein levels caused by obesity. These results suggest that ET can prevent weight gain and pathological cardiac hypertrophy via increased of cardiac MED13 by the regulation of miRNA-208a. Therefore, miRNA-208a can be used as potential therapeutic target for metabolic and cardiac disorders.

Corrigendum to "Exercise Training Restores Cardiac MicroRNA-1 and MicroRNA-29c to Nonpathological Levels in Obese Rats".

[This corrects the article DOI: 10.1155/2017/1549014.].

Exercise Training Restores the Cardiac Microrna-16 Levels Preventing Microvascular Rarefaction in Obese Zucker Rats.

OBJECTIVE: To evaluate the effects of aerobic exercise training (AET) on cardiac miRNA-16 levels and its target gene VEGF related to microvascular rarefaction in obese Zucker rats (OZR). METHODS: OZR (n = 11) and lean (L; n = 10) male rats were assigned into 4 groups: OZR, trained OZR (OZRT), L and trained L (LT). Swimming exercise training lasted 60 min, 1×/day/10 weeks, with 4% body weight workload. Cardiac angiogenesis was assessed by histological analysis (periodic acid-Schiff) by calculating the capillary/fiber ratio. The protein expressions of VEGF, VEGFR2, and CD31 were evaluated by western blot. The expression of miRNA-16 was evaluated by real-time PCR. RESULTS: Heart rate decreased in the trained groups compared to sedentary groups. The cardiac capillary/fiber ratio was reduced in OZR compared to L, LT and OZRT groups, indicating that aerobic exercise training (AET) was capable of reversing the microvascular rarefaction in the obese animals. miRNA-16 expression was increased in OZR compared to L, LT and OZRT. In contrast, its target, VEGF protein expression was 24% lower in OZR compared to L group, which has been normalized in OZRT group. VEGFR2 protein expression was increased in trained groups compared to their controls. CD31, a endothelial cells marker, showed increased expression in OZRT compared to OZR, indicating greater vascularization in OZRT group. CONCLUSION: AET induced cardiac angiogenesis in obese animals. This revascularization is associated with a decrease in miRNA-16 expression permissive for increased VEGF protein expression, suggesting a mechanism for potential therapeutic application in vascular diseases.

Exercise Training Restores Cardiac MicroRNA-1 and MicroRNA-29c to Nonpathological Levels in Obese Rats.

We previously reported that aerobic exercise training (AET) consisted of 10 weeks of 60-min swimming sessions, and 5 days/week AET counteracts CH in obesity. Here, we evaluated the role of microRNAs and their target genes that are involved in heart collagen deposition and calcium signaling, as well as the cardiac remodeling induced by AET in obese Zucker rats. Among the four experimental Zucker groups: control lean rats (LZR), control obese rats (OZR), trained lean rats (LZR + TR), and trained obese rats (OZR + TR), heart weight was greater in the OZR than in the LZR group due to increased cardiac intramuscular fat and collagen. AET seems to exert a protective role in normalizing the heart weight in the OZR + TR group. Cardiac microRNA-29c expression was decreased in OZR compared with the LZR group, paralleled by an increase in the collagen volumetric fraction (CVF). MicroRNA-1 expression was upregulated while the expression of its target gene NCX1 was decreased in OZR compared with the LZR group. Interestingly, AET restored cardiac microRNA-1 to nonpathological levels in the OZR-TR group. Our findings suggest that AET could be used as a nonpharmacological therapy for the reversal of pathological cardiac remodeling and cardiac dysfunction in obesity.

Obesity Downregulates MicroRNA-126 Inducing Capillary Rarefaction in Skeletal Muscle: Effects of Aerobic Exercise Training.

Background. We investigated the effects of exercise training (ET) on miR-126 levels and skeletal muscle angiogenesis in obese Zucker rats. Results. Zucker rats were randomly assigned to sedentary and swimming-trained groups: lean sedentary (LS) and trained (LTR); obese sedentary (OB) and trained (OBTR). The OB group displayed capillary rarefaction compared with the LS group. In contrast, ET increased the capillary/fiber ratio by 38% in the LTR group and normalized capillary rarefaction in the OBTR group. VEGF, PI3K, and eNOS levels were reduced in the skeletal muscle of the OB group. ET normalized VEGF, PI3K, and eNOS levels in OBTR, contributing to vascular network homeostasis. PI3KR2 inhibits PI3K, a key mediator of the VEGF signaling pathway. Obesity decreased miR-126 and increased PI3KR2 levels compared with the LS group. However, ET normalized miR-126 levels in the OBTR group versus the LS group and decreased expression of PI3KR2. Conclusion. Our findings show that obesity leads to skeletal muscle capillary rarefaction, which is regulated by decreased miR-126 levels and increased PI3KR2. Inversely, ET normalizes miR-126 levels and VEGF signaling and should be considered an important therapeutic strategy for vascular disorders.

Effects of aerobic exercise training on cardiac renin-angiotensin system in an obese Zucker rat strain.

OBJECTIVE: Obesity and renin angiotensin system (RAS) hyperactivity are profoundly involved in cardiovascular diseases, however aerobic exercise training (EXT) can prevent obesity and cardiac RAS activation. The study hypothesis was to investigate whether obesity and its association with EXT alter the systemic and cardiac RAS components in an obese Zucker rat strain. METHODS: THE RATS WERE DIVIDED INTO THE FOLLOWING GROUPS: Lean Zucker rats (LZR); lean Zucker rats plus EXT (LZR+EXT); obese Zucker rats (OZR) and obese Zucker rats plus EXT (OZR+EXT). EXT consisted of 10 weeks of 60-min swimming sessions, 5 days/week. At the end of the training protocol heart rate (HR), systolic blood pressure (SBP), cardiac hypertrophy (CH) and function, local and systemic components of RAS were evaluated. Also, systemic glucose, triglycerides, total cholesterol and its LDL and HDL fractions were measured. RESULTS: The resting HR decreased (∼12%) for both LZR+EXT and OZR+EXT. However, only the LZR+EXT reached significance (p<0.05), while a tendency was found for OZR versus OZR+EXT (p = 0.07). In addition, exercise reduced (57%) triglycerides and (61%) LDL in the OZR+EXT. The systemic angiotensin I-converting enzyme (ACE) activity did not differ regardless of obesity and EXT, however, the OZR and OZR+EXT showed (66%) and (42%), respectively, less angiotensin II (Ang II) plasma concentration when compared with LZR. Furthermore, the results showed that EXT in the OZR prevented increase in CH, cardiac ACE activity, Ang II and AT2 receptor caused by obesity. In addition, exercise augmented cardiac ACE2 in both training groups. CONCLUSION: Despite the unchanged ACE and lower systemic Ang II levels in obesity, the cardiac RAS was increased in OZR and EXT in obese Zucker rats reduced some of the cardiac RAS components and prevented obesity-related CH. These results show that EXT prevented the heart RAS hyperactivity and cardiac maladaptive morphological alterations in obese Zucker rats.

Treinamento físico aeróbio previne à hipertrofia cardíaca patológica e melhora a função diastólica em ratos Zucker obesos / Aerobic exercise training revert pathologic cardiac hypertrophy and improves the diastolic function in obese Zucker rats

A obesidade é uma patologia diretamente relacionada com o desenvolvimento de doenças cardiovasculares. Por outro lado, o treinamento físico aeróbio atenua o desenvolvimento da obesidade e promove benefícios cardíacos em obesos. Dessa forma, nosso objetivo foi investigar se a obesidade altera a função cardíaca e se sua associação com o treinamento físico aeróbio promove melhora na função cardíaca em ratos Zucker obesos. Os ratos Zucker foram divididos da seguinte forma: grupo magro (GM), grupo obeso (GO), grupo magro treinado (GMTR) e grupo obeso treinado (GOTR). O protocolo de treinamento aeróbio de natação foi realizado por um período de 10 semanas com cinco sessões semanais de 60 minutos de duração. A frequência cardíaca de repouso, a pressão arterial sistólica, a hipertrofia e função cardíaca foram avaliadas no final do período de treinamento físico. Ambos os grupos treinados apresentaram uma queda de 12 por cento da frequência cardíaca de repouso, quando comparado com seus respectivos controles. Ainda, nossos resultados demonstraram que o treinamento aeróbio reduziu o aumento da massa cardíaca em 13 por cento e melhorou a função diastólica na obesidade em 43 por cento. Em conclusão, nossos dados demonstraram que o treinamento físico aeróbio reverteu os prejuízos cardíacos causados pela obesidade.

Obesity is profoundly involved in cardiovascular diseases. On the other hand, aerobic exercise training (EXT) attenuates obesity and promotes cardiac benefits in obese individuals. Therefore, the aim of this study was to investigate if obesity alters the cardiac function and whether its association with exercise training can improve cardiac function in an obese Zucker rat strain. The rats were divided in the following groups: Lean Zucker rats (LZR); lean Zucker rats plus exercise training (LZR+EXT); obese Zucker rat (OZR) and obese Zucker rat plus exercise training (OZR+EXT). EXT consisted of 10 weeks swimming sessions of 60 min, 5 days/week. At the end of the training protocol we evaluated heart rate (HR), systolic blood pressure (SBP), cardiac hypertrophy (CH) and function. The trained groups LZR+EXT and OZR+EXT showed a 12 percent lower resting HR when compared with theirs respective controls. In addition, our results showed that exercise training reduced the cardiac mass by 13 percent and improved the diastolic function by 43 percent in the obese trained group when compared with the obese untrained. In conclusion, aerobic exercise training reverts the cardiac injuries in obese Zucker rats.

Exercício de força ativa a via AKT/mTor pelo receptor de angiotensina II tipo I no músculo cardíaco de ratos / Activation of AKT-mTor signaling pathways by angiotensin II receptor type 1 after a session of strength exercise in cardiac muscle of rats

O receptor de angiotensina II tipo I (AT1) tem uma importante participação no desenvolvimento da hipertrofia cardíaca. Em um trabalho publicado anteriormente, por nosso grupo, demonstramos que o bloqueio do receptor AT1 durante o treinamento de força inibiu a hipertrofia cardíaca em ratos. Por isso, o objetivo deste trabalho foi estudar a participação do receptor AT1 na ativação de vias de sinalização intracelular relacionadas com o aumento da síntese de proteína em ratos submetidos a uma sessão de exercício de força. Para isso, realizamos um experimento com seis grupos de animais (n = 6; cada): controle (Con), exercitado e sacrificado cinco minutos após o exercício (Exe 5), exercitado e sacrificado 30 minutos após o exercício (Exe 30), controle tratado com losartan (Con Los), tratado com losartan, exercitado e sacrificado cinco minutos após o exercício (Exe 5 Los), tratado com losartan, exercitado e sacrificado 30 minutos após o exercício (Exe 30 Los). Os resultados mostram que no grupo Exe 5 e Exe 30 ocorreu um aumento de 63 por cento (P < 0,05) e 62 por cento (P < 0,05), respectivamente, na fosforilação da proteína AKT comparado com o grupo controle. Enquanto a fosforilação da mTor foi aumentada 65 por cento (P < 0,05) somente no grupo Exe 30 comparado com o grupo controle, sendo estes efeitos bloqueados pelo uso do losartan nos grupos Exe 5 Los e Exe 30 Los. Portanto, esses resultados, juntamente com nossos resultados prévios, demonstram que o receptor AT1 tem participação na ativação da AKT e mTOR após uma sessão de exercício de força.

The angiotensin II type I (AT1) receptor has an important participation in the development of cardiac hypertrophy. Previously, we have shown that AT1 receptor participates in the cardiac hypertrophy induced by resistance training in rats. Here, we studied the involvement of AT1 receptor in the activation of intracellular signaling pathways related to the concentric HC in rats submitted to a session of strength exercise. Male Wistar rats were divided into 6 groups (n= 6 each): control (Con); exercised and killed 5 minutes after exercise (Exe 5); exercised and killed 30 minutes after exercise (Exe 30); control treated with Losartan (Con Los); treated with Losartan, exercised and killed 5 minutes after the exercise (Exe Los 5); treated with Losartan, exercised and killed 30 minutes after training (Exe Los 30). The results show that phosphorylation activity of AKT in group Exe 5 and Exe 30 increased 63 percent (P < 0.05) and 62 percent (P < 0.05), respectively, compared with Con. Whereas the phosphorylation of mTOR was increased 65 percent (P < 0.05), compared to Con, only in the group Exe 30. Furthermore, these effects were blocked by losartan treatment in groups Exe Los 5 and Exe Los 30. These results, together with ours previous data shows that the AT1 receptor has an role in the activation of AKT and mTOR pathway after a session of strength exercise.

O papel do esteroide anabolizante sobre a hipertrofia e força muscular em treinamentos de resistência aeróbia e de força / The role of anabolic steroids on hypertrophy and muscular

INTRODUÇÃO: Os efeitos dos esteroides anabolizantes (EA) sobre a massa muscular e força são controversos e dependentes do treinamento realizado e das fibras musculares recrutadas. Com isso, o objetivo deste estudo foi avaliar os efeitos da associação de EA ao treinamento de força ou aeróbio sobre a hipertrofia e força muscular. MÉTODOS: Ratos Wistar (42) foram divididos em seis grupos: sedentário (SC, n = 7), sedentário anabolizante (SA, n = 7), treinado natação controle (TNC, n = 7), treinado natação anabolizante (TNA, n = 7), treinado força controle (TFC, n = 7) e treinado força anabolizante (TFA, n = 7). O EA foi administrado duas vezes por semana (10mg/kg/semana). Os protocolos de treinamento foram realizados durante 10 semanas, cinco sessões semanais. Foram avaliadas a hipertrofia dos músculos sóleo, plantar e gastrocnêmio (massa muscular corrigida pelo comprimento da tíbia), a proteína total muscular (Bradford) e a força muscular em patas traseiras (testes de resistência à inclinação). RESULTADOS: Não foram observadas diferenças significantes na hipertrofia do músculo sóleo. Os grupos TFC e TFA apresentaram, respectivamente, hipertrofia de 18 por cento e 31 por cento no músculo plantar comparado ao grupo SC. A hipertrofia foi 13 por cento maior no grupo TFA em relação ao grupo TFC. Resultados semelhantes foram encontrados no músculo gastrocnêmio. Os grupos TFC e TFA apresentaram significantes aumentos na quantidade total de proteína nos músculos plantares, sendo essa mais pronunciada no grupo TFA e positivamente correlaciona a hipertrofia muscular. Observamos aumento de força nas patas traseiras nos grupos TCF e TAF. CONCLUSÃO: A administração de EA ou sua associação ao treinamento aeróbio não aumenta a massa muscular e força. Porém, à associação ao treinamento de força leva a maior hipertrofia muscular em fibras glicolíticas. Portanto, o tipo de treinamento físico, recrutamento muscular e características das fibras musculares...

INTRODUCTION: The effects of the anabolic steroids (AS) on muscle mass and strength are controversial and dependent on the training protocol performed and the muscle fibers recruited. Thus, the aim of this study was to evaluate the AS effects combined with strength training or aerobic exercise training on muscle hypertrophy and strength. METHODS: Wistar rats (42) were divided into six groups: sedentary control (SC, n = 7), steroid sedentary (SS, n = 7), swimming training control (STC, n = 7), swimming training steroid (STS, n = 7), strength training control (SRC, n = 7) and strength training steroid (SRS, n = 7). AS was administered twice a week (10mg/kg/week). The training protocols were performed for 10 weeks, 5 sessions per week. Soleus, gastrocnemius and plantar hypertrophy (muscle mass corrected for tibia length), total muscle protein (Bradford) and muscle strength in hind limb (resistance to twist) were assessed. RESULTS: No significant differences were observed in soleus muscle hypertrophy. SRC and SRS groups showed hypertrophy of 18 percent and 31 percent in plantar muscles compared to the SC group. Hypertrophy was 13 percent higher in SRS than SRC group. Similar results were found in gastrocnemius muscle. SRC and SRS groups showed significant increases in the protein total amount in the plantar muscles, it was more pronounced in SRS group and positively correlated to muscle hypertrophy. The strength was increase in SRC and SRS groups. CONCLUSION: AS administration or its association to aerobic training does not increase muscle mass and strength. However, its association to strength training leads to muscle hypertrophy in glycolytic fibers. Therefore, the physical training protocol, muscle recruitment and muscle fibers characteristics, appear to have significant impact on anabolic responses induced by AS.

Anabolic steroid associated to physical training induces deleterious cardiac effects.

PURPOSE: Cardiac aldosterone might be involved in the deleterious effects of nandrolone decanoate (ND) on the heart. Therefore, we investigated the involvement of cardiac aldosterone, by the pharmacological block of AT1 or mineralocorticoid receptors, on cardiac hypertrophy and fibrosis. METHODS: Male Wistar rats were randomized into eight groups (n = 14 per group): Control (C), nandrolone decanoate (ND), trained (T), trained ND (TND), ND + losartan (ND + L), trained ND + losartan (TND + L), ND + spironolactone (ND + S), and trained ND + spironolactone (TND + S). ND (10 mg·kg(-1)·wk(-1)) was administered during 10 wk of swimming training (five times per week). Losartan (20 mg·kg(-1)·d(-1)) and spironolactone (10 mg·kg(-1)·d(-1)) were administered in drinking water. RESULTS: Cardiac hypertrophy was increased 10% by using ND and 17% by ND plus training (P < 0.05). In both groups, there was an increase in the collagen volumetric fraction (CVF) and cardiac collagen type III expression (P < 0.05). The ND treatment increased left ventricle-angiotensin-converting enzyme I activity, AT1 receptor expression, aldosterone synthase (CYP11B2), and 11-ß hydroxysteroid dehydrogenase 2 (11ß-HSD2) gene expression and inflammatory markers, TGFß and osteopontin. Both losartan and spironolactone inhibited the increase of CVF and collagen type III. In addition, both treatments inhibited the increase in left ventricle-angiotensin-converting enzyme I activity, CYP11B2, 11ß-HSD2, TGFß, and osteopontin induced by the ND treatment. CONCLUSIONS: We believe this is the first study to show the effects of ND on cardiac aldosterone. Our results suggest that these effects may be associated to TGFß and osteopontin. Thus, we conclude that the cardiac aldosterone has an important role on the deleterious effects on the heart induced by ND.