Leandro Pereira de Moura

Exercise counteracts fatty liver disease in rats fed on fructose-rich diet

BackgroundThis study aimed to analyze the effects of exercise at the aerobic/anaerobic transition on the markers of non-alcoholic fatty liver disease (NAFLD), insulin sensitivity and the blood chemistry of rats kept on a fructose-rich diet.MethodsWe separated 48 Wistar rats into two groups according to diet: a control group (balanced diet AIN-93 G) and a fructose-rich diet group (60% fructose). The animals were tested for maximal lactate-steady state (MLSS) in order to identify the aerobic/anaerobic metabolic transition during swimming exercises at 28 and 90 days of age. One third of the animals of each group were submitted to swimming training at an intensity equivalent to the individual MLSS for 1 hours/day, 5 days/week from 28 to 120 days (early protocol). Another third were submitted to the training from 90 to 120 days (late protocol), and the others remained sedentary. The main assays performed included an insulin tolerance test (ITT) and tests of serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST] activities, serum triglyceride concentrations [TG] and liver total lipid concentrations.ResultsThe fructose-fed rats showed decreased insulin sensitivity, and the late-exercise training protocol counteracted this alteration. There was no difference between the groups in levels of serum ALT, whereas AST and liver lipids increased in the fructose-fed sedentary group when compared with the other groups. Serum triglycerides concentrations were higher in the fructose-fed trained groups when compared with the corresponding control group.ConclusionsThe late-training protocol was effective in restoring insulin sensitivity to acceptable standards. Considering the markers here evaluated, both training protocols were successful in preventing the emergence of non-alcoholic fatty liver status disease.

Exercise and spirulina control non-alcoholic hepatic steatosis and lipid profile in diabetic Wistar rats

BackgroundDiabetes mellitus is associated with metabolic dysfunctions, including alterations in circulating lipid levels and fat tissue accumulation, which causes, among other pathologies, non-alcoholic fatty liver disease (NAFLD).Aim of the studyThe objective of this study was to analyse the effects of physical exercise and spirulina intake on the control of NAFLD in diabetic Wistar rats.MethodsDiabetes was induced in the animals through intravenous administration of alloxan. The rats were divided into four groups: Diabetic Control (DC) - diabetic rats fed with a control diet and no physical exercise; Diabetic Spirulina (DS) - diabetic rats fed with a diet that included spirulina; Diabetic Spirulina and Exercise (DSE) - diabetic rats fed with a diet that included Spirulina and that exercised; and Diabetic Exercise (DE) - diabetic rats fed with a control diet and that exercised.ResultsThe groups DS, DSE, and DE presented lower plasma concentrations of LDL cholesterol than DC, as well as lower levels of total liver lipids in groups DS, DSE, and DE in comparison to DC.ConclusionThus, spirulina appears to be effective in reducing total circulating levels of LDL-cholesterol and hepatic lipids, alone or in conjunction with physical exercise in diabetic rats.

Effects of Exercise Training on Hippocampus Concentrations of Insulin and IGF-1 in Diabetic Rats

The present study investigated the role of swimming training on cerebral metabolism and hippocampus concentrations of insulin and IGF‐1 in diabetic rats. Wistar rats were divided in sedentary control (SC), trained control (TC), sedentary diabetic (SD), and trained diabetic (TD). Diabetes was induced by Alloxan (35 mg kg−1 b.w.). Training program consisted in swimming 5 days/week, 1 h/day, 8 weeks, supporting a load corresponding to 90% of maximal lactate steady state (MLSS). For MLSS determination, rats were submitted to three sessions of 25‐min supporting loads of 4, 5, or 6% of body wt, with intervals of 1 week. Blood samples were collected every 5 min for lactate determination. An acute exercise test (25 min to 90% of MLSS) was done in 7th week to confirm the efficacy of training. All dependent variables were analyzed by one‐way analysis of variance (ANOVA) and a significance level of P < 0.05 was used for all comparisons. The Bonferroni test was used for post hoc comparisons. At the end of the training period, rats were sacrificed and sample blood was collected for determinations of serum glucose, insulin, GH, and IGF‐1. Samples of gastrocnemius muscle and liver were removed to evaluate glycogen content. Hippocampus was extracted to determinate glycogen, insulin, and IGF‐1 contents. Diabetes decreased serum GH, IGF‐1, and liver glycogen stores in SD. Diabetes also increased hippocampus glycogen and reduced hippocampus IGF‐1 content. Physical training recovered liver and hippocampus glycogen stores and promoted increases in serum IGF‐1 in TD group. Physical training restored hippocampus IGF‐1 content in diabetic group. It was concluded that in diabetic rats, physical training induces important metabolic and hormonal alterations that areassociated with an improvement in glucose homeostasis and with an increased activity in the systemic and hippocampus IGF‐1 peptide.

Growth factors and glucose homeostasis in diabetic rats: effects of exercise training

To investigate the alterations of glucose homeostasis and variables of the insulin‐like growth factor‐1 (IGF‐1) growth system in sedentary and trained diabetic (TD) rats, Wistar rats were divided into sedentary control (SC), trained control (TC), sedentary diabetic (SD), and TD groups. Diabetes was induced by Alloxan (35 mg kg−1 b.w.). Training program consisted of swimming 5 days week−1, 1 h day−1, during 8 weeks. Rats were sacrificed and blood was collected for determinations of serum glucose, insulin, growth hormone (GH), IGF‐1, and IGF binding protein‐3 (IGFBP‐3). Muscle and liver were removed to evaluate glycogen content. Cerebellum was extracted to determinate IGF‐1 content. Diabetes decreased serum GH, IGF‐1, IGFBP‐3, liver glycogen, and cerebellum IGF‐1 peptide content in baseline condition. Physical training recovered liver glycogen and increased serum and cerebellum IGF‐1 peptide in diabetic rats. Physical training induces important metabolic and hormonal alterations that are associated with an improvement in glucose homeostasis and serum and cerebellum IGF‐1 concentrations. Copyright

Strength Training Prevents Hyperinsulinemia, Insulin Resistance, and Inflammation Independent of Weight Loss in Fructose-Fed Animals.

The aim of this study was to compare the effects of aerobic, strength, and combined training on metabolic disorders induced by a fructose-rich diet. Wistar rats (120 days old) were randomized into five groups (n = 8–14): C (control diet and sedentary), F (fed the fructose-rich diet and sedentary), FA (fed the fructose-rich diet and subject to aerobic exercise), FS (fed the fructose-rich diet and subject to strength exercise), and FAS (fed the fructose-rich diet and subject to combined aerobic and strength exercises). After the 8-week experiment, glucose homeostasis, blood biochemistry, tissue triglycerides, and inflammation were evaluated and analyzed. The strength protocol exerted greater effects on glucose homeostasis, insulin sensitivity, and liver lipid contents than other protocols (all P < 0.05). All three exercise protocols induced a remarkable reduction in inflammation, tissue triglyceride content, and inflammatory pathways, which was achieved through c-Jun NH2-terminal kinase (JNK) phosphorylation and factor nuclear kappa B (NFkB) activation in both the liver and the muscle. Our data suggest that strength training reduced the severity of most of the metabolic disorders induced by a fructose-rich diet and could be the most effective strategy to prevent or treat fructose-induced metabolic diseases.

Exercise training decreases mitogen-activated protein kinase phosphatase-3 expression and suppresses hepatic gluconeogenesis in obese mice

When the hepatic insulin signaling is compromised, there is an inadequate suppression of gluconeogenic pathways, leading the organism to high levels of glucose. Studies with animals with obesity induced by high fat diet or genetically modified showed increased MKP‐3 expression and MKP‐3/Foxo1 association in liver, with a consequent increase in blood glucose concentration, development of insulin resistance and DM2. As a non‐pharmacological strategy recognized and indicated for prevention and treatment of diabetes is the regular practice of physical exercise. In this study we demostrated that physical training is an important tool capable of reducing insulin resistance in the liver by reducing the inflammatory process, including the inhibition of MKP‐3 and, therefore, suppress gluconeogenic program in obesity rats. The understanding of these new mechanisms by which physical training regulates glucose homeostasis has critical importance to health professionals for the understanding and prevention of diabetes.

Treadmill Training Increases SIRT-1 and PGC-1α Protein Levels and AMPK Phosphorylation in Quadriceps of Middle-Aged Rats in an Intensity-Dependent Manner

The present study investigated the effects of running at 0.8 or 1.2 km/h on inflammatory proteins (i.e., protein levels of TNF-α, IL-1β, and NF-κB) and metabolic proteins (i.e., protein levels of SIRT-1 and PGC-1α, and AMPK phosphorylation) in quadriceps of rats. Male Wistar rats at 3 (young) and 18 months (middle-aged rats) of age were divided into nonexercised (NE) and exercised at 0.8 or 1.2 km/h. The rats were trained on treadmill, 50 min per day, 5 days per week, during 8 weeks. Forty-eight hours after the last training session, muscles were removed, homogenized, and analyzed using biochemical and western blot techniques. Our results showed that: (a) running at 0.8 km/h decreased the inflammatory proteins and increased the metabolic proteins compared with NE rats; (b) these responses were lower for the inflammatory proteins and higher for the metabolic proteins in young rats compared with middle-aged rats; (c) running at 1.2 km/h decreased the inflammatory proteins and increased the metabolic proteins compared with 0.8 km/h; (d) these responses were similar between young and middle-aged rats when trained at 1.2 km. In summary, the age-related increases in inflammatory proteins, and the age-related declines in metabolic proteins can be reversed and largely improved by treadmill training.

Spatial memory in sedentary and trained diabetic rats: Molecular mechanisms

Diabetes mellitus is a chronic disease that has been associated with memory loss, neurological disorders, and Alzheimers disease. Some studies show the importance of physical exercise to prevent and minimize various neurological disorders. It is believed that the positive effects of exercise on brain functions are mediated by brain insulin and insulin‐like growth factor‐1 (IGF‐1) signaling. In this study, we investigate the role of swimming exercise training on hippocampus proteins related to insulin/IGF‐1 signaling pathway in Type 1 diabetic rats and its effects on spatial memory. Wistar rats were divided into four groups namely sedentary control, trained control, sedentary diabetic (SD), and trained diabetic (TD). Diabetes was induced by Alloxan (ALX) (32 mg/kg b.w.). The training program consisted in swimming 5 days/week, 1 h/day, per 6 weeks, supporting an overload corresponding to 90% of the anaerobic threshold. We employed ALX‐induced diabetic rats to explore learning and memory abilities using Morris water maze test. At the end of the training period, the rats were sacrificed 48 h after their last exercise bout when blood samples were collected for serum glucose, insulin, and IGF‐1 determinations. Hippocampus was extracted to determinate protein expression (IR, IGF‐1R, and APP) and phosphorylation (AKT‐1, AKT‐2, Tau, and β‐amyloide proteins) by Western Blot analysis. All dependent variables were analyzed by two‐way analysis of variance with significance level of 5%. Diabetes resulted in hyperglycemia and hypoinsulinemia in both SD and TD groups (P < 0.05); however, in the training‐induced group, there was a reduction in blood glucose in TD. The average frequency in finding the platform decreased in SD rats; however, exercise training improved this parameter in TD rats. Aerobic exercise decreased Tau phosphorylation and APP expression, and increased some proteins related to insulin/IGF‐1 pathway in hippocampus of diabetic rats. Thus, these molecular adaptations from exercise training might contribute to improved spatial learning and memory in diabetic organisms.

Creatine supplementation and oxidative stress in rat liver

BackgroundThe objective of this study was to determine the effects of creatine supplementation on liver biomarkers of oxidative stress in exercise-trained rats.MethodsForty 90-day-old adult male Wistar rats were assigned to four groups for the eight-week experiment. Control group (C) rats received a balanced control diet; creatine control group (CCr) rats received a balanced diet supplemented with 2% creatine; trained group (T) rats received a balanced diet and intense exercise training equivalent to the maximal lactate steady state phase; and supplemented-trained (TCr) rats were given a balanced diet supplemented with 2% creatine and subjected to intense exercise training equivalent to the maximal lactate steady state phase. At the end of the experimental period, concentrations of creatine, hydrogen peroxide (H2O2) and thiobarbituric acid reactive substances (TBARS) were measured as well as the enzyme activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-GPx) and catalase (CAT). Liver tissue levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and the GSH/GSSG ratio were also determined.ResultsHepatic creatine levels were highest in the CCr and TCr groups with increased concentration of H2O2 observed in the T and TCr animal groups. SOD activity was decreased in the TCr group. GSH-GPx activity was increased in the T and TCr groups while CAT was elevated in the CCr and TCr groups. GSH, GGS and the GSH/GSSG ratio did not differ between all animal subsets.ConclusionsOur results demonstrate that creatine supplementation acts in an additive manner to physical training to raise antioxidant enzymes in rat liver. However, because markers of liver oxidative stress were unchanged, this finding may also indicate that training-induced oxidative stress cannot be ameliorated by creatine supplementation.

Acute exercise decreases PTP-1B protein level and improves insulin signaling in the liver of old rats

It is now commonly accepted that chronic inflammation associated with obesity during aging induces insulin resistance in the liver. In the present study, we investigated whether the improvement in insulin sensitivity and insulin signaling, mediated by acute exercise, could be associated with modulation of protein-tyrosine phosphatase 1B (PTP-1B) in the liver of old rats. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45 min rest period. Sixteen hours after the exercise, the rats were sacrificed and proteins from the insulin signaling pathway were analyzed by immunoblotting. Our results show that the fat mass was increased in old rats. The reduction in glucose disappearance rate (Kitt) observed in aged rats was restored 16 h after exercise. Aging increased the content of PTP-1B and attenuated insulin signaling in the liver of rats, a phenomenon that was reversed by exercise. Aging rats also increased the IRβ/PTP-1B and IRS-1/PTP-1B association in the liver when compared with young rats. Conversely, in the liver of exercised old rats, IRβ/PTP-1B and IRS-1/PTP-1B association was markedly decreased. Moreover, in the hepatic tissue of old rats, the insulin signalling was decreased and PEPCK and G6Pase levels were increased when compared with young rats. Interestingly, 16 h after acute exercise, the PEPCK and G6Pase protein level were decreased in the old exercised group. These results provide new insights into the mechanisms by which exercise restores insulin signalling in liver during aging.