Physical Exercise Decreases Fasting Hyperglycemia in Diabetic Mice Through AMPK Activation

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.15317918

IL-6 and IL-10 Anti-Inflammatory Activity Links Exercise to Hypothalamic Insulin and Leptin Sensitivity through IKK beta and ER Stress Inhibition

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Overnutrition caused by overeating is associated with insulin and leptin resistance through IKK beta activation and endoplasmic reticulum (ER) stress in the hypothalamus. Here we show that physical exercise suppresses hyperphagia and associated hypothalamic IKK beta/NF-k beta activation by a mechanism dependent upon the pro-inflammatory cytokine interleukin (IL)-6. The disruption of hypothalamic-specific IL-6 action blocked the beneficial effects of exercise on the re-balance of food intake and insulin and leptin resistance. This molecular mechanism, mediated by physical activity, involves the anti-inflammatory protein IL-10, a core inhibitor of IKK beta/NF-k beta signaling and ER stress. We report that exercise and recombinant IL-6 requires IL-10 expression to suppress hyperphagia-related obesity. Moreover, in contrast to control mice, exercise failed to reverse the pharmacological activation of IKK beta and ER stress in C3H/HeJ mice deficient in hypothalamic IL-6 and IL-10 signaling. Hence, inflammatory signaling in the hypothalamus links beneficial physiological effects of exercise to the central action of insulin and leptin.88Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Central Exercise Action Increases the AMPK and mTOR Response to Leptin

AMP-activated protein kinase (AMPK) and mammalian Target of Rapamycin (mTOR) are key regulators of cellular energy balance and of the effects of leptin on food intake. Acute exercise is associated with increased sensitivity to the effects of leptin on food intake in an IL-6-dependent manner. To determine whether exercise ameliorates the AMPK and mTOR response to leptin in the hypothalamus in an IL-6-dependent manner, rats performed two 3-h exercise bouts, separated by one 45-min rest period. Intracerebroventricular IL-6 infusion reduced food intake and pretreatment with AMPK activators and mTOR inhibitor prevented IL-6-induced anorexia. Activators of AMPK and fasting increased food intake in control rats to a greater extent than that observed in exercised ones, whereas inhibitor of AMPK had the opposite effect. Furthermore, the reduction of AMPK and ACC phosphorylation and increase in phosphorylation of proteins involved in mTOR signal transduction, observed in the hypothalamus after leptin infusion, were more pronounced in both lean and diet-induced obesity rats after acute exercise. Treatment with leptin reduced food intake in exercised rats that were pretreated with vehicle, although no increase in responsiveness to leptin-induced anorexia after pretreatment with anti-IL6 antibody, AICAR or Rapamycin was detected. Thus, the effects of leptin on the AMPK/mTOR pathway, potentiated by acute exercise, may contribute to appetite suppressive actions in the hypothalamus

Leucine supplementation improves adiponectin and total cholesterol concentrations despite the lack of changes in adiposity or glucose homeostasis in rats previously exposed to a high-fat diet

<p>Abstract</p> <p>Background</p> <p>Studies suggest that leucine supplementation (LS) has a therapeutic potential to prevent obesity and to promote glucose homeostasis. Furthermore, regular physical exercise is a widely accepted strategy for body weight maintenance and also for the prevention of obesity. The aim of this study was to determine the effect of chronic LS alone or combined with endurance training (ET) as potential approaches for reversing the insulin resistance and obesity induced by a high-fat diet (HFD) in rats.</p> <p>Methods</p> <p>Forty-seven rats were randomly divided into two groups. Animals were fed a control diet-low fat (<it>n = </it>10) or HFD (<it>n = </it>37). After 15 weeks on HFD, all rats received the control diet-low fat and were randomly divided according to treatment: reference (REF), LS, ET, and LS+ET (<it>n = </it>7-8 rats per group). After 6 weeks of treatment, the animals were sacrificed and body composition, fat cell volume, and serum concentrations of total cholesterol, HDL-cholesterol, triacylglycerol, glucose, adiponectin, leptin and tumor necrosis factor-alpha (TNF-α) were analyzed.</p> <p>Results</p> <p>At the end of the sixth week of treatment, there was no significant difference in body weight between the REF, LS, ET and LS+ET groups. However, ET increased lean body mass in rats (<it>P </it>= 0.019). In addition, ET was more effective than LS in reducing adiposity (<it>P </it>= 0.019), serum insulin (<it>P </it>= 0.022) and TNF-α (<it>P </it>= 0.044). Conversely, LS increased serum adiponectin (<it>P </it>= 0.021) levels and reduced serum total cholesterol concentration (<it>P </it>= 0.042).</p> <p>Conclusions</p> <p>The results showed that LS had no beneficial effects on insulin sensitivity or adiposity in previously obese rats. On the other hand, LS was effective in increasing adiponectin levels and in reducing total cholesterol concentration.</p

Gut-central nervous system axis is a target for nutritional therapies

Historically, in the 1950s, the chemist Linus Pauling established a relationship between decreased longevity and obesity. At this time, with the advent of studies involving the mechanisms that modulate appetite control, some researchers observed that the hypothalamus is the "appetite centre" and that peripheral tissues have important roles in the modulation of gut inflammatory processes and levels of hormones that control food intake. Likewise, the advances of physiological and molecular mechanisms for patients with obesity, type 2 diabetes mellitus, inflammatory bowel diseases, bariatric surgery and anorexia-associated diseases has been greatly appreciated by nutritionists. Therefore, this review highlights the relationship between the gut-central nervous system axis and targets for nutritional therapies