Endurance training prevents inflammation and apoptosis in hypothalamic neurons of obese mice.

This study investigated the effects of exercise training in regulating inflammatory processes, endoplasmic reticulum stress, and apoptosis in hypothalamic neurons of obese mice. Swiss mice were distributed into three groups: Lean mice (Lean), sedentary animals fed a standard diet; obese mice (Obese), sedentary animals fed a high-fat diet (HFD); trained obese mice (T. Obese), animals fed with HFD and concurrently subjected to an endurance training protocol for 8 weeks. In the endurance training protocol, mice ran on a treadmill at 60% of peak workload for 1 hr, 5 days/week for 8 weeks. Twenty-four hours after the last exercise session, the euthanasia was performed. Western blot, quantitative real-time polymerase chain reaction, and terminal deoxynucleotide transferase biotin-dUTP nick end-labeling (TUNEL) techniques were used for the analysis of interest. The results show exercise training increased phosphorylation of leptin signaling pathway proteins (pJAK2/pSTAT3) and reduced the content of tumor necrosis factor α, toll-like receptor 4, suppressor of cytokine signaling 3, protein-tyrosine phosphatase 1B as well as the phosphorylation of IkB kinase in the hypothalamus of T. Obese animals. A reduction of macrophage activation and phosphorylation of eukaryotic initiation factor 2α, and protein kinase RNA-like endoplasmic reticulum kinase (PERK) were also observed in exercised animals. Furthermore, exercise decreased the expression of the proapoptotic protein (PARP1) and increased anti-inflammatory (IL-10) and antiapoptotic (Bcl2) proteins. Using the TUNEL technique, we observed that the exercised animals had lower DNA fragmentation. Finally, physical exercise preserved pro-opiomelanocortin messenger RNA content. In conclusion, exercise training was able to reorganize the control of the energy balance through anti-inflammatory and antiapoptotic responses in hypothalamic tissue of obese mice.

Exercício físico reduz a hiperglicemia de jejum em camundongos diabéticos através da ativação da AMPK / Physical exercise decreases fasting hyperglycemia in diabetic mice through AMPK activation

INTRODUÇÃO: A deficiência na captação de glicose em tecidos periféricos e o aumento da gliconeogênese hepática são fenômenos fisiopatológicos observados em pacientes diabéticos do tipo 2. O exercício físico é considerado um importante aliado para a melhora do perfil glicêmico em pacientes diabéticos; entretanto, os mecanismos envolvidos nesse processo não estão completamente elucidados. OBJETIVO: Avaliar o papel da proteína AMPK no controle glicêmico em camundongos diabéticos após o exercício físico. MÉTODOS: Durante o jejum, o teste de tolerância à insulina (ITT) e a técnica de Western blot foram combinados para avaliar a homeostase da glicose em camundongos diabéticos (ob/ob e db/db) submetidos a uma única sessão de natação. RESULTADOS: A hiperglicemia de jejum, a severa resistência à insulina e a deficiência na sinalização da via AMPK/ACC no músculo e no fígado observadas nos camundongos diabéticos foram revertidas após a sessão de exercício. A restauração da via AMPK/ACC reduziu a expressão da enzima gliconeogênica PEPCK no fígado e aumentou a translocação do GLUT4 no músculo esquelético. Esses dados apontam que a ativação da via AMPK/ACC induzida pelo exercício físico é importante para a redução da glicemia de jejum em modelos experimentais de diabetes tipo 2. Esses dados abrem novas frentes para o entendimento de como a atividade física controla da homeostase da glicose em pacientes diabéticos.

INTRODUCTION: The deficiency in glucose uptake in peripheral tissues and increased hepatic gluconeogenesis are physiopathological phenomena observed in type 2 diabetes patients. Physical exercise plays an important role in the improvement of glycemic profile in diabetic patients; however, the mechanisms involved in these processes have not been fully elucidated. OBJECTIVE: to assess the role of AMPK protein in the glycemic control of diabetic mice after exercise. METHODS: During fasting condition, the insulin tolerance test (ITT) and Western blot technique, were combined to assess the glucose homeostasis in diabetic mice (ob/ob and db/db) after a single swimming session. RESULTS: Fasting hyperglycemia, severe insulin resistance and deficiency in the AMPK/ACC signaling in muscle and liver observed in the diabetic mice were reversed after the exercise session. The restoration of AMPK/ACC signaling reduced the expression of the gluconeogenic enzyme, PEPCK in the liver, and increased the translocation of GLUT4 in the skeletal muscle. These data indicate that the activation of AMPK/ACC pathway induced by physical exercise is important to reduce fasting glucose levels in experimental models of type 2 diabetes. These data open new insights for determination of physical activity control on the glucose homeostasis in diabetic patients.