Preventive role of exercise training in autonomic, hemodynamic, and metabolic parameters in rats under high risk of metabolic syndrome development

Preventive role of exercise training in autonomic, hemodynamic, and metabolic parameters in rats under high risk of metabolic syndrome development. J Appl Physiol 114: 786-791, 2013. First published January 17, 2013; doi:10.1152/japplphysiol.00586.2012.-High fructose consumption contributes to metabolic syndrome incidence, whereas exercise training promotes several beneficial adaptations. in this study, we demonstrated the preventive role of exercise training in the metabolic syndrome derangements in a rat model. Wistar rats receiving fructose overload in drinking water (100 g/l) were concomitantly trained on a treadmill (FT) or kept sedentary (F) for 10 wk. Control rats treated with normal water were also submitted to exercise training (CT) or sedentarism (C). Metabolic evaluations consisted of the Lee index and glycemia and insulin tolerance test (kITT). Blood pressure (BP) was directly measured, whereas heart rate (HR) and BP variabilities were evaluated in time and frequency domains. Renal sympathetic nerve activity was also recorded. F rats presented significant alterations compared with all the other groups in insulin resistance (in mg.dl(-1).min(-1): F: 3.4 +/- 0.2; C: 4.7 +/- 0.2; CT: 5.0 +/- 0.5 FT: 4.6 +/- 0.4), mean BP (in mmHG: F: 117 +/- 2; C: 100 +/- 2; CT: 98 +/- 2; FT: 105 +/- 2), and Lee index (in g/mm: F = 0.31 +/- 0.001; C = 0.29 +/- 0.001; CT = 0.27 +/- 0.002; FT = 0.28 +/- 0.002), confirming the metabolic syndrome diagnosis. Exercise training blunted all these derangements. Additionally, FS group presented autonomic dysfunction in relation to the others, as seen by an similar to 50% decrease in baroreflex sensitivity and 24% in HR variability, and increases in sympathovagal balance (140%) and in renal sympathetic nerve activity (45%). These impairments were not observed in FT group, as well as in C and CT. Correlation analysis showed that both Lee index and kITT were associated with vagal impairment caused by fructose. Therefore, exercise training plays a preventive role in both autonomic and hemodynamic alterations related to the excessive fructose consumption.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ São Paulo, Sch Med, Heart Inst InCor, Hypertens Unit, BR-05403900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Nephrol, São Paulo, BrazilNove Julho Univ, São Paulo, BrazilUniv Prebiteriana Mackenzie, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Nephrol, São Paulo, BrazilWeb of Scienc

Interactions between p-Akt and Smad3 in injured muscles initiate myogenesis or fibrogenesis

In catabolic conditions such as aging and diabetes, IGF signaling is impaired and fibrosis develops in skeletal muscles. To examine whether impaired IGF signaling initiates muscle fibrosis, we generated IGF-IR+/- heterozygous mice by crossing loxP-floxed IGF-IR (exon 3) mice with MyoD-cre mice. IGF-IR+/- mice were studied because we were unable to obtain homozygous IGF-IR-KO mice. in IGF-IR+/- mice, both growth and expression of myogenic genes (MyoD and myogenin; markers of satellite cell proliferation and differentiation, respectively) were depressed. Likewise, in injured muscles of IGF-IR+/- mice, there was impaired regeneration, depressed expression of MyoD and myogenin, and increased expression of TGF-beta 1, alpha-SMA, collagen I, and fibrosis. To uncover mechanisms stimulating fibrosis, we isolated satellite cells from muscles of IGF-IR+/- mice and found reduced proliferation and differentiation plus increased TGF-beta 1 production. in C2C12 myoblasts (a model of satellite cells), IGF-I treatment inhibited TGF-beta 1-stimulated Smad3 phosphorylation, its nuclear translocation, and expression of fibronectin. Using immunoprecipitation assay, we found an interaction between p-Akt or Akt with Smad3 in wild-type mouse muscles and in C2C12 myoblasts; importantly, IGF-I increased p-Akt and Smad3 interaction, whereas TGF-beta 1 decreased it. Therefore, in muscles of IGF-IR+/- mice, the reduction in IGF-IR reduces p-Akt, allowing for dissociation and nuclear translocation of Smad3 to enhance the TGF-beta 1 signaling pathway, leading to fibrosis. Thus, strategies to improve IGF signaling could prevent fibrosis in catabolic conditions with impaired IGF signaling.Satellite HealthAmerican Diabetes AssociationNational Institute of Diabetes and Digestive and Kidney DiseasesBaylor Coll Med, Div Nephrol, Dept Med, Houston, TX 77030 USAEmory Univ, Dept Med, Div Renal, Atlanta, GA 30322 USACapital Med Univ, Beijing An Zhen Hosp, Beijing Inst Heart Lung & Blood Vessel Dis, Beijing, Peoples R ChinaUniversidade Federal de São Paulo, Div Nephrol, Dept Med, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Dept Med, São Paulo, BrazilAmerican Diabetes Association: 1-11-BS-194National Institute of Diabetes and Digestive and Kidney Diseases: R37-DK-37175National Institute of Diabetes and Digestive and Kidney Diseases: T32-DK-62706Web of Scienc

Exercise Attenuates Renal Dysfunction with Preservation of Myocardial Function in Chronic Kidney Disease

Previous studies have suggested that exercise improves renal and cardiac functions in patients with chronic kidney disease. the aim of this study was to evaluate the effects of long-term aerobic swimming exercise with overload on renal and cardiac function in rats with 5/6 nefrectomy (5/6Nx). Eight Wistar rats were placed into 4 groups: Control (C), Control+Exercise (E), Sedentary 5/6Nx (NxS) and 5/6Nx+Exercise (NxE). the rats were subjected to swimming exercise sessions with overload for 30 min five days per week for five weeks. Exercise reduced the effect of 5/6Nx on creatinine clearance compared to the NxS group. in addition, exercise minimized the increase in mean proteinuria compared to the NxS group (96.9 +/- 10.0 vs. 51.4 +/- 9.9 mg/24 h; p<0.05). Blood pressure was higher in the NxS and NxE groups compared to the C and E groups (216 +/- 4 and 178 +/- 3 vs. 123 +/- 2 and 124 +/- 2 mm Hg, p<0.05). in the 200 glomeruli that were evaluated, the NxS group had a higher sclerosis index than did the NxE group (16% vs. 2%, p<0.05). Echocardiography demonstrated a higher anterior wall of the left ventricle (LV) in diastole in the NxS group compared with the C, E and NxE groups. the NxS group also had a higher LV posterior wall in diastole and systole compared with the E group. the developed isometric tension in Lmax of the heart papillary muscle was lower in the NxS group compared with the C, E and NxE groups. These results suggested that exercise in 5/6Nx animals might reduce the progression of renal disease and lessen the cardiovascular impact of a reduction in renal mass.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundacao Oswaldo Ramos (FOR)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, UNIFESP EPM, Dept Med, Div Nephrol, São Paulo, BrazilUniversidade Federal de São Paulo, Cardiophysiol & Pathophysiol Lab, São Paulo, BrazilUniv São Paulo, Sch Med, Heart Inst InCor, Lab Genet & Mol Cardiol, São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP EPM, Dept Med, Div Nephrol, São Paulo, BrazilUniversidade Federal de São Paulo, Cardiophysiol & Pathophysiol Lab, São Paulo, BrazilWeb of Scienc

Previous Exercise Training Has a Beneficial Effect on Renal and Cardiovascular Function in a Model of Diabetes

Exercise training (ET) is an important intervention for chronic diseases such as diabetes mellitus (DM). However, it is not known whether previous exercise training intervention alters the physiological and medical complications of these diseases. We investigated the effects of previous ET on the progression of renal disease and cardiovascular autonomic control in rats with streptozotocin (STZ)-induced DM. Male Wistar rats were divided into five groups. All groups were followed for 15 weeks. Trained control and trained diabetic rats underwent 10 weeks of exercise training, whereas previously trained diabetic rats underwent 14 weeks of exercise training. Renal function, proteinuria, renal sympathetic nerve activity (RSNA) and the echocardiographic parameters autonomic modulation and baroreflex sensitivity (BRS) were evaluated. In the previously trained group, the urinary albumin/creatinine ratio was reduced compared with the sedentary diabetic and trained diabetic groups (p &lt; 0.05). Additionally, RSNA was normalized in the trained diabetic and previously trained diabetic animals (p &lt; 0.05). The ejection fraction was increased in the previously trained diabetic animals compared with the diabetic and trained diabetic groups (p &lt; 0.05), and the myocardial performance index was improved in the previously trained diabetic group compared with the diabetic and trained diabetic groups (p &lt; 0.05). In addition, the previously trained rats had improved heart rate variability and BRS in the tachycardic response and bradycardic response in relation to the diabetic group (p &lt; 0.05). This study demonstrates that previous ET improves the functional damage that affects DM. Additionally, our findings suggest that the development of renal and cardiac dysfunction can be minimized by 4 weeks of ET before the induction of DM by STZ.Fundacao de Amparo a Pesquisa do Estado de Sao PauloFundacao de Amparo a Pesquisa do Estado de Sao PauloConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Fundacao Oswaldo RamosFundacao Oswaldo RamosCNPq-Bolsa de Produtividade em pesquisa (BPQ)CNPqBolsa de Produtividade em pesquisa (BPQ

Home Dust Mites Promote MUC5AC Hyper-Expression by Modulating the sNASP/TRAF6 Axis in the Airway Epithelium

House dust mites (HDMs) are a common source of respiratory allergens responsible for allergic asthma and innate immune responses in human diseases. Since HDMs are critical factors in the triggering of allergen-induced airway mucosa from allergic asthma, we aimed to investigate the mechanisms of Toll-like receptors (TLR) in the signaling of the HDM extract that is involved in mucus hypersecretion and airway inflammation through the engagement of innate immunity. Previously, we reported that the somatic nuclear autoantigenic sperm protein (sNASP)/tumor necrosis factor receptor-associated factor 6 (TRAF6) axis controls the initiation of TLRs to maintain the homeostasis of the innate immune response. The present study showed that the HDM extract stimulated the biogenesis of Mucin 5AC (MUC5AC) in bronchial epithelial cells via the TLR2/4 signaling pathway involving MyD88 and TRAF6. Specifically, sNASP binds to TRAF6 in unstimulated bronchial epithelial cells to prevent the activation of TRAF6-depenedent kinases. Upon on HDMs&rsquo; stimulation, sNASP is phosphorylated, leading to the activation of TRAF6 downstream of the p38 MAPK and NF-&kappa;B signaling pathways. Further, NASP-knockdown enhanced TRAF6 signaling and MUC5AC biogenesis. In the HDM-induced mouse asthma model, we found that the HDM extract promoted airway hyperresponsiveness (AHR), MUC5AC, and allergen-specific IgE production as well as IL-5 and IL-13 for recruiting inflammatory cells. Treatment with the PEP-NASP peptide, a selective TRAF6-blocking peptide, ameliorated HDM-induced asthma in mice. In conclusion, this study indicated that the sNASP/TRAF6 axis plays a regulatory role in asthma by modulating mucus overproduction, and the PEP-NASP peptide might be a potential target for asthma treatment