Rodrigo Ferreira de Moura

Metabolic syndrome signs in Wistar rats submitted to different high-fructose ingestion protocols

In search of an adequate model for the human metabolic syndrome, the metabolic characteristics of Wistar rats were analysed after being submitted to different protocols of high fructose ingestion. First, two adult rat groups (aged 90 d) were studied: a control group (C1; n 6) received regular rodent chow (Labina, Purina) and a fructose group (F1; n 6) was fed on regular rodent chow. Fructose was administered as a 10 % solution in drinking water. Second, two adult rat groups (aged 90 d) were evaluated: a control group (C2; n 6) was fed on a balanced diet (AIN-93G) and a fructose group (F2; n 6) was fed on a purified 60 % fructose diet. Finally, two young rat groups (aged 28 d) were analysed: a control group (C3; n 6) was fed on the AIN-93G diet and a fructose group (F3; n 6) was fed on a 60 % fructose diet. After 4-8 weeks, the animals were evaluated. Glucose tolerance, peripheral insulin sensitivity, blood lipid profile and body fat were analysed. In the fructose groups F2 and F3 glucose tolerance and insulin sensitivity were lower, while triacylglycerolaemia was higher than the respective controls C2 and C3 (P < 0.05). Blood total cholesterol, HDL and LDL as well as body fat showed change only in the second protocol. In conclusion, high fructose intake is more effective at producing the signs of the metabolic syndrome in adult than in young Wistar rats. Additionally, diet seems to be a more effective way of fructose administration than drinking water.

Fractalkine (CX3CL1) Is Involved in the Early Activation of Hypothalamic Inflammation in Experimental Obesity

Hypothalamic inflammation is a common feature of experimental obesity. Dietary fats are important triggers of this process, inducing the activation of toll-like receptor-4 (TLR4) signaling and endoplasmic reticulum stress. Microglia cells, which are the cellular components of the innate immune system in the brain, are expected to play a role in the early activation of diet-induced hypothalamic inflammation. Here, we use bone marrow transplants to generate mice chimeras that express a functional TLR4 in the entire body except in bone marrow–derived cells or only in bone marrow–derived cells. We show that a functional TLR4 in bone marrow–derived cells is required for the complete expression of the diet-induced obese phenotype and for the perpetuation of inflammation in the hypothalamus. In an obesity-prone mouse strain, the chemokine CX3CL1 (fractalkine) is rapidly induced in the neurons of the hypothalamus after the introduction of a high-fat diet. The inhibition of hypothalamic fractalkine reduces diet-induced hypothalamic inflammation and the recruitment of bone marrow–derived monocytic cells to the hypothalamus; in addition, this inhibition reduces obesity and protects against diet-induced glucose intolerance. Thus, fractalkine is an important player in the early induction of diet-induced hypothalamic inflammation, and its inhibition impairs the induction of the obese and glucose intolerance phenotypes.

n-3 Fatty Acids Induce Neurogenesis of Predominantly POMC-Expressing Cells in the Hypothalamus.

Apoptosis of hypothalamic neurons is believed to play an important role in the development and perpetuation of obesity. Similar to the hippocampus, the hypothalamus presents constitutive and stimulated neurogenesis, suggesting that obesity-associated hypothalamic dysfunction can be repaired. Here, we explored the hypothesis that n-3 polyunsaturated fatty acids (PUFAs) induce hypothalamic neurogenesis. Both in the diet and injected directly into the hypothalamus, PUFAs were capable of increasing hypothalamic neurogenesis to levels similar or superior to the effect of brain-derived neurotrophic factor (BDNF). Most of the neurogenic activity induced by PUFAs resulted in increased numbers of proopiomelanocortin but not NPY neurons and was accompanied by increased expression of BDNF and G-protein–coupled receptor 40 (GPR40). The inhibition of GPR40 was capable of reducing the neurogenic effect of a PUFA, while the inhibition of BDNF resulted in the reduction of global hypothalamic cell. Thus, PUFAs emerge as a potential dietary approach to correct obesity-associated hypothalamic neuronal loss.

Acute effect of static stretching on rate of force development and maximal voluntary contraction in older women.

Gurjão, ALD, Gonçalves, R, de Moura, RF, and Gobbi, S. Acute effect of static stretching on rate of force development and maximal voluntary contraction in older women. J Strength Cond Res 23(7): 2149-2154, 2009-The purpose of this study was to investigate, in older women, the acute effect of static stretching (SS) on both muscle activation and force output. Twenty-three older women (64.6 ± 7.1 yr) participated in the study. The maximal voluntary contraction (MVC), rate of force development (RFD) (50, 100, 150, and 200 ms relative to onset of muscular contraction), and peak RFD (PRFD) (the steepest slope of the curve during the first 200 ms) were tested under 2 randomly separate conditions: SS and control (C). Electromyographic (EMG) activity of the vastus medialis (VM), vastus lateralis (VL), and biceps femoris (BF) muscles also was assessed. The MVC was significantly lower (p < 0.05) in the 3 trials of SS when compared with the C condition (control: 925.0 ± 50.9 N; trial 1: 854.3 ± 55.3 N; trial 2: 863.1 ± 52.2 N; and trial 3: 877.5 ± 49.9 N). PRFD showed a significant decrease only for the first 2 trials of SS when compared with the C condition (control: 2672.3 ± 259.1 N/s; trial 1: 2296.6 ± 300.7 N/s; and trial 2: 2197.9 ± 246.3 N/s). However, no difference was found for RFD (50, 100, 150, and 200 ms relative to onset of muscular contraction). The EMG activity for VM, VL, and BF was not significantly different between the C and SS conditions. In conclusion, the older womens capacity to produce muscular force decreased after their performance of SS exercises. The mechanisms responsible for this effect do not appear to be related to muscle activation. Thus, if flexibility is to be trained, it is recommended that SS does not occur just before the performance of activities that require high levels of muscular force.

Defective Regulation of the Ubiquitin/Proteasome System in the Hypothalamus of Obese Male Mice

In both human and experimental obesity, inflammatory damage to the hypothalamus plays an important role in the loss of the coordinated control of food intake and energy expenditure. Upon prolonged maintenance of increased body mass, the brain changes the defended set point of adiposity, and returning to normal weight becomes extremely difficult. Here we show that in prolonged but not in short-term obesity, the ubiquitin/proteasome system in the hypothalamus fails to maintain an adequate rate of protein recycling, leading to the accumulation of ubiquitinated proteins. This is accompanied by an increased colocalization of ubiquitin and p62 in the arcuate nucleus and reduced expression of autophagy markers in the hypothalamus. Genetic protection from obesity is accompanied by the normal regulation of the ubiquitin/proteasome system in the hypothalamus, whereas the inhibition of proteasome or p62 results in the acceleration of body mass gain in mice exposed for a short period to a high-fat diet. Thus, the defective regulation of the ubiquitin/proteasome system in the hypothalamus may be an important mechanism involved in the progression and autoperpetuation of obesity.

TLR4 Expression in Bone Marrow-Derived Cells Is Both Necessary and Sufficient to Produce the Insulin Resistance Phenotype in Diet-Induced Obesity

The anomalous activation of toll-like receptor 4 (TLR4) by dietary fats is one of the most important mechanisms linking obesity to insulin resistance. TLR4 is expressed in most tissues of the body, but its activity in the cells of the immune system is expected to underlie its most important roles of inducing inflammation and insulin resistance. Here we explore the hypothesis that TLR4 expression in bone marrow-derived cells mediates most of the actions of this receptor as an inducer of insulin resistance. Wild type and TLR4-mutant mice were used in bone marrow transplant experiments producing chimeras that harbored the functional receptor in all cells of the body except bone marrow-derived cells or only in bone marrow-derived cells. Transplanted mice were fed chow or a high-fat diet, and glucose homeostasis was evaluated by glucose and insulin tolerance tests. Insulin signal transduction and the expression of markers of inflammation were evaluated in the liver and white adipose tissue. In addition, we performed liver histology and evaluated the expression of gluconeogenic enzymes. The expression of TLR4 in bone marrow-derived cells only, but not in non-bone marrow-derived tissues only, was a determining factor in the induction of diet-induced insulin resistance, which was accompanied by an increased expression of inflammatory markers in both white adipose tissue and liver as well as increased liver steatosis and increased expression of gluconeogenic enzymes. TLR4 expressed in bone marrow-derived cells is an important mediator of obesity-associated insulin resistance in mice.

Long-term physical training increases liver IGF-I in diabetic rats

Diabetes reduces the serum levels of insulin-like growth factor-I (IGF-I) and physical training may prevent this reduction. Almost all circulating IGF-I is produced and secreted by the liver. To examine the influence of moderate physical training on liver IGF-1 levels in diabetes, male Wistar rats were given a single dose of alloxan (30 mg/kg b.w.) to induce diabetes and then randomly allocated to sedentary or trained groups. The training protocol consisted of a 1h swimming session/day, five days/week for eight weeks with a load corresponding to 5% of the body weight. These two groups were compared with sedentary or trained non-diabetic rats (controls). A subcutaneous insulin tolerance test (ITT) was performed at the 6th week of experiment. At the end of the training period, the rats in all groups were sacrificed and blood was collected for the quantification of hematocrit and serum glucose, insulin, triglycerides, albumin, GH and IGF-1. Skeletal muscle and hepatic glycogen levels and hepatic triglyceride, protein, DNA and IGF-I concentrations were also determined. Diabetes reduced the serum insulin, GH and IGF-I concentrations, and the hepatic protein/DNA ratio and IGF-I concentrations, but increased serum glucose and triglyceride levels. Serum glucose removal during ITT was increased in the trained diabetic animals compared to sedentary control. Physical training reduced the serum glucose and triglyceride levels but increased the muscle glycogen content and restored the hepatic protein/DNA ratio and serum and hepatic IGF-I in diabetic rats. In conclusion, long-term chronic exercise improved the metabolic state and attenuated the reduction in serum and hepatic IGF-I concentrations caused by diabetes.

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

Capacidade aeróbia de ratos alimentados com dieta rica em frutose

INTRODUCAO: Evidencias apontam que a ingestao exacerbada de frutose pode desencadear disturbios caracteristicos da sindrome metabolica. OBJETIVOS: Analisar os efeitos da ingestao de dieta rica em frutose sobre aspectos metabolicos de ratos da linhagem Wistar. Adicionalmente, verificar a capacidade aerobia atraves da identificacao da maxima fase estavel de lactato (MFEL). METODOS: Dezesseis ratos foram separados em dois grupos de oito animais: a) controle, alimentados com dieta balanceada, e b) frutose, alimentados com dieta rica em frutose. Foram analisadas a tolerância a glicose (area sob a curva de glicose durante teste de tolerância a glicose), sensibilidade a insulina (taxa de remocao da glicose serica apos sobrecarga exogena de insulina), perfil lipidico serico e concentracao de lactato sanguineo [lac]s durante exercicio na intensidade da MFEL. RESULTADOS: Teste t nao pareado (p < 0,05) revelou diferenca para a tolerância a glicose e triglicerides, porem nao houve diferenca na sensibilidade a insulina e na [lac]s. Anova one way com post hoc de Newman-Keuls (p < 0,05) revelou diferenca para a cinetica da glicose durante o teste de tolerância, mas nao para a cinetica do lactato durante exercicio na MSSL. CONCLUSAO: As Alteracoes fisiologicas provocadas pela dieta rica em frutose e inerentes a sindrome metabolica nao prejudicam a capacidade aerobia de ratos.INTRODUCTION: Evidence points that exacerbated ingestion of fructose may trigger disturbs characteristic of the metabolic syndrome. OBJECTIVES: To analyze the effects of a fructose rich diet on metabolic aspects of Wistar lineage rats. Additionally, to verify the aerobic capacity, through the identification of the maximal lactate steady state (MSSL). PROCEDURES: Sixteen rats were separated in two groups of eight animals: a) Control, fed a balanced diet, and b) fructose, fed a fructose-rich diet. The glucose tolerance, (area under serum glucose during a glucose tolerance test), insulin sensibility (glucose disappearance rate after exogenous insulin administration), serum lipid profile and blood lactate concentration [lac]b during exercise at MSSL intensity, have been analyzed. RESULTS: Non-paired t test (p<0.05) revealed difference between groups in the area under the curve of glucose and serum triglycerides, no difference in insulin sensibility or in [lac]b was detected, though. One-way ANOVA with Newman Keuls post hoc revealed difference in the glucose kinetics during tolerance test, but not in the lactate kinetics during the MSSL. CONCLUSION: The physiological alterations promoted by fructose-rich diet and intrinsic to the metabolic syndrome do not harm the aerobic capacity of rats.

Effect of strength training on rate of force development in older women.

We analyzed the effect of an 8-week strength training (ST) program on the rate of force development (RFD) and electromyographic activity (EMG) in older women. Seventeen women (M age = 63.4 years, SD = 4.9) without previous ST experience were randomly assigned to either a control (n = 7) or training (n = 10) group. A leg-press isometric test was used for assessment. ST (three sessions/ week, three sets of 10–12 repetition maximum, five different exercises) induced significant increases (p < .05) on peak RFD (48.4%) and on RFD and EMG of vastus medialis at time intervals of 0–50, 0–100, 0–150, and 0–200 ms (41.1–69.2% and 43.8– 64.3%, respectively). Therefore, ST resulted in favorable changes in neuromuscular responses in older women.