Effects of Moderate- and High-Intensity Chronic Exercise on the Adiponectin Levels in Slow-Twitch and Fast-Twitch Muscles in Rats.

Background and objectives: Adipose tissue and skeletal muscle secrete adiponectin, a hormone abundantly secreted by adipocytes, that through the adiponectin receptor, regulate glucose and lipid metabolism. Adiponectin appears to protect skeletal muscles from inflammatory damage induced by oxidative stress. It has been suggested that decreased adiponectin levels could be associated with pathologic conditions, including obesity and diabetes. Furthermore, some studies suggest that exercise could have a beneficial effect by increasing adiponectin levels, but this observation remains controversial. It is also unknown if physical exercise modifies adiponectin expression in skeletal muscles. The aim of this study was to investigate the effect of chronic exercise on serum adiponectin and adiponectin expression in slow-twitch (soleus) and fast-twitch (plantaris) muscles in healthy rats. Materials and methods: Two-month-old male Wistar rats were randomly divided into three groups with n = 6 in each group: control (C), moderate-intensity training (MIT), and high-intensity training (HIT). The rats were conditioned to run on a treadmill for the 8-week period. Forty-eight hours after the last session, blood samples were collected for adiponectin measurements and total RNA was isolated from plantaris and soleus muscles to measure by RT-qPCR adiponectin receptor 1 and adiponectin mRNA expression level. Results: MIT and HIT groups had reduced adiponectin protein levels in serum and the plantaris muscle, but not changes in adiponectin protein were observed in the soleus muscle. No significant differences in Adiponectin receptor 1 (AdipoR1) gene expression were observed following intense or moderate exercise in either muscle group studied. Conclusions: Our study shows that decreasing levels of circulating adiponectin is a result of physical exercise and should not be generalized as a predictive marker of disease.

Matrix Metalloproteinases System and Types of Fibrosis in Rat Heart during Late Pregnancy and Postpartum.

Background and objectives: Cardiac remodeling in pregnancy and postpartum is poorly understood. The aim of this study was to evaluate changes in cardiac fibrosis (pericardial, perivascular, and interstitial), as well as the expression of matrix metalloproteinases (MMP-1, MMP-2, and MMP-9) and their inhibitors (Tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-4) during late pregnancy and postpartum in rat left ventricle. Materials and Methods: Female Sprague-Dawley rats were used for this study. Rats were divided three groups: non-pregnant, late pregnancy, and postpartum. The heart was weighed and cardiac fibrosis was studied by conventional histological procedures. The expression and transcript level of target proteins were evaluated using immunoblot techniques and quantitative PCR. Results: The experiments showed an increase of perivascular, pericardial, and interstitial fibrosis in heart during pregnancy and its reversion in postpartum. Moreover, in late pregnancy, MMP-1, MMP-2, and MMP-9 metalloproteinases were downregulated and TIMP-1 and TIMP-4 were upregulated in left ventricle. Conclusions: Our data suggest that the metalloproteinases system is involved in the cardiac extracellular matrix remodeling during pregnancy and its reversion in postpartum, this improves the knowledge of the adaptive cardiac remodeling in response to a blood volume overload present during pregnancy.

Neurobiología de la depresión mayor y de su tratamiento farmacológico / Neurobiology of major depression and its pharmacologic treatment

Resumen: INTRODUCCIÓN: La depresión mayor (DM) se debe a la interacción de factores ambientales, genéticos y epigenéticos, que atenúan la transmisión monoaminérgica en el cerebro. Sin embargo, poco se conoce sobre los mecanismos fisiopatológicos que subyacen a ella. OBJETIVO: Proponer una visión integral sobre la fisiopatología de la DM y los mecanismos de acción de los fármacos antidepresivos. MÉTODO: Se empleó la base PubMed para la búsqueda bibliográfica. La mayoría son investigaciones experimentales y estudios de genética molecular o de imágenes cerebrales en humanos. RESULTADOS: La DM se asocia con: i) menor volumen de la corteza cingulada anterior; ii) hiper-metabolismo del área Cg25; iii) menor expresión del receptor 5-HT1A; iv) mayor expresión de la monoamino oxidasa A. Algunos polimorfismos están asociados a la fisiopatología. El estrés crónico reduce la expresión del 5-HT1A. Los antidepresivos atenúan el hiper-metabolismo del área Cg25, estimulan la neurogénesis y activan la vía del AMPc. Encontramos que la imipramina aumenta y reduce la expresión de G α s y G α z, respectivamente (datos sin publicar). DISCUSIÓN Y CONCLUSIÓN: El déficit en la transmisión monoaminérgica puede deberse a: i) el polimorfismo G1463A en el gen de la enzima hTPH2 que reduce la síntesis de serotonina; ii) el polimorfismo C(-1019)G en el gen del receptor 5-HT1A, aumentando su transcripción en el rafé e implicando menor liberación del neurotransmisor; iii) mayor degradación de las monoaminas. La menor expresión del receptor 5-HT1A se discute considerando su acción inhibitoria en la corteza prefrontal. Los cambios en la expresión de G α s y G α z coinciden con la estimulación de la vía del AMPc.

Abstract: INTRODUCTION: The major depressive disorder (MDD) arises from the interaction of environmental, genetic and epigenetic factors, producing a deficit in monoaminergic transmission within the brain. However, our understanding of its pathophysiology is quite limited. OBJECTIVE: To reach an integrative view of the MDD pathophysiology, as well as the mechanisms of action of antidepressant drugs. METHOD: We used the PubMed database to search for the documents by using the appropriate key words. Most of them are experimental research and molecular genetics and brain imaging studies in humans. RESULTS: The pathophysiology of MDD is characterized by: i) shrinkage of the cingulate anterior cortex; ii) hyper-metabolism of the Cg25 area; iii) lower expression of the 5-HT1A receptor; iv) enhanced expression of monoamine oxidase A. Besides, certain gene polymorphisms are strongly linked to the pathophysiology, and there is evidence that 5-HT1A receptor expression is reduced by psychological stress. Antidepressants reverse the hyper-metabolic state of Cg25, stimulate neurogenesis and the cAMP pathway. We found that imipramine increases and reduces the expression of G α s and G α z, respectively (data no published). DISCUSSION AND CONCLUSION: The disruption in monoaminergic transmission could be mediated by: i) the G1463A hTPH2 polymorphism that reduces the serotonin synthesis; ii) the C(-1019)G 5-HT1A polymorphism that increases the receptor expression in the dorsal rafe, and reduces serotonin release; iii) an increase in monoamine degradation. The reduced 5-HT1A expression is discussed considering its inhibitory properties in the prefrontal cortex. The effects of imipramine on G α s and G α z are in agreement with the antidepressant-induced stimulation of the cAMP pathway.

Effects of moderate- and high-intensity chronic exercise on brain-derived neurotrophic factor expression in fast and slow muscles.

INTRODUCTION: Brain-derived neurotrophic factor (BDNF) protein expression is sensitive to cellular activity. In the sedentary state, BDNF expression is affected by the muscle phenotype. METHODS: Eighteen Wistar rats were divided into the following 3 groups: sedentary (S); moderate-intensity training (MIT); and high-intensity training (HIT). The training protocol lasted 8 weeks. Forty-eight hours after training, total RNA and protein levels in the soleus and plantaris muscles were obtained. RESULTS: In the plantaris, the BDNF protein level was lower in the HIT than in the S group (P < 0.05). A similar effect was found in the soleus (without significant difference). In the soleus, higher Bdnf mRNA levels were found in the HIT group (P < 0.001 vs. S and MIT groups). In the plantaris muscle, similar Bdnf mRNA levels were found in all groups. CONCLUSIONS: These results indicate that high-intensity chronic exercise reduces BDNF protein level in fast muscles and increases Bdnf mRNA levels in slow muscles.

Vasculitis cutánea paraneoplásica asociada a cáncer de pulmón / Paraneoplastic Cutaneous Vasculitis Associated With Lung Cancer

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Chronic exercise increases plasma brain-derived neurotrophic factor levels, pancreatic islet size, and insulin tolerance in a TrkB-dependent manner.

BACKGROUND: Physical exercise improves glucose metabolism and insulin sensitivity. Brain-derived neurotrophic factor (BDNF) enhances insulin activity in diabetic rodents. Because physical exercise modifies BDNF production, this study aimed to investigate the effects of chronic exercise on plasma BDNF levels and the possible effects on insulin tolerance modification in healthy rats. METHODS: Wistar rats were divided into five groups: control (sedentary, C); moderate- intensity training (MIT); MIT plus K252A TrkB blocker (MITK); high-intensity training (HIT); and HIT plus K252a (HITK). Training comprised 8 weeks of treadmill running. Plasma BDNF levels (ELISA assay), glucose tolerance, insulin tolerance, and immunohistochemistry for insulin and the pancreatic islet area were evaluated in all groups. In addition, Bdnf mRNA expression in the skeletal muscle was measured. PRINCIPAL FINDINGS: Chronic treadmill exercise significantly increased plasma BDNF levels and insulin tolerance, and both effects were attenuated by TrkB blocking. In the MIT and HIT groups, a significant TrkB-dependent pancreatic islet enlargement was observed. MIT rats exhibited increased liver glycogen levels following insulin administration in a TrkB-independent manner. CONCLUSIONS/SIGNIFICANCE: Chronic physical exercise exerted remarkable effects on insulin regulation by inducing significant increases in the pancreatic islet size and insulin sensitivity in a TrkB-dependent manner. A threshold for the induction of BNDF in response to physical exercise exists in certain muscle groups. To the best of our knowledge, these are the first results to reveal a role for TrkB in the chronic exercise-mediated insulin regulation in healthy rats.

Carnitine palmitoyltransferase 1B 531K allele carriers sustain a higher respiratory quotient after aerobic exercise, but ß3-adrenoceptor 64R allele does not affect lipolysis: a human model.

Carnitine palmitoyltransferase IB (CPT1B) and adrenoceptor beta-3 (ADRB3) are critical regulators of fat metabolism. CPT1B transports free acyl groups into mitochondria for oxidation, and ADRB3 triggers lipolysis in adipocytes, and their respective polymorphisms E531K and W64R have been identified as indicators of obesity in population studies. It is therefore important to understand the effects of these mutations on ADRB3 and CPT1B function in adipose and skeletal muscle tissue, respectively. This study aimed to analyze the rate of lipolysis of plasma indicators (glycerol, free fatty acids, and beta hydroxybutyrate) and fat oxidation (through the non-protein respiratory quotient). These parameters were measured in 37 participants during 30 min of aerobic exercise at approximately 62% of maximal oxygen uptake, followed by 30 min of recovery. During recovery, mean respiratory quotient values were higher in K allele carriers than in non-carriers, indicating low post-exercise fatty acid oxidation rates. No significant differences in lipolysis or lipid oxidation were observed between R and W allele carriers of ADRB3 at any time during the aerobic load. The substitution of glutamic acid at position 531 by lysine in the CPT1B protein decreases the mitochondrial beta-oxidation pathway, which increases the non-protein respiratory quotient value during recovery from exercise. This may contribute to weight gain or reduced weight-loss following exercise.