Effects of Diet and Exercise on Endocrine Function of Skeletal Muscle

Skeletal muscle has been recognized as an endocrine tissue that releases appreciable amounts of circulating proteins, called myokines. Currently, we know that the skeletal muscles synthesize several hundreds of peptides classified as myokines, and muscle contraction stimulates their release [1,2]. Myokines can act in autocrine, paracrine or endocrine mode and there is an increasing number of data showing that they can affect different organs and tissues, e.g., the brain, bones, adipocyte tissue, heart artery, and many others [3]. For instance, the interleukins IL-6 and IL-10, released by the muscles during exercise, exert powerful local and systemic anti-inflammatory effects. Furthermore, IL-10 has been shown to provide cardio-and neuroprotection, which is mediated by the activation of anti-apoptotic protein kinase B (PKB or Akt) [4,5]. In addition, myokines like SPARC and oncostatin M show inhibitory activity against colon and breast cancer cells, respectively. Skeletal muscles represent the largest organ of the human body (the muscles constitute approximately 40% of total body mass), thus their role in the regulation of metabolic processes via myokines appears to be very important. Unfortunately, there is a limited amount of data demonstrating the effects of nutraceuticals on exercise-induced release of myokines. It has been shown that release of IL-6 from skeletal muscle was inhibited in persons supplemented with vitamin C and E. We hypothesize that natural compounds may exert their protective activity against some human diseases by modulating myokine synthesis

Swim Training Modulates Skeletal Muscle Energy Metabolism, Oxidative Stress, and Mitochondrial Cholesterol Content in Amyotrophic Lateral Sclerosis Mice

Recently, in terms of amyotrophic lateral sclerosis (ALS), much attention has been paid to the cell structures formed by the mitochondria and the endoplasmic reticulum membranes (MAMs) that are involved in the regulation of Ca2+ signaling, mitochondrial bioenergetics, apoptosis, and oxidative stress. We assumed that remodeling of these structures via swim training may accompany the prolongation of the ALS lifespan. In the present study, we used transgenic mice with the G93A hmSOD1 gene mutation. We examined muscle energy metabolism, oxidative stress parameters, and markers of MAMs (Caveolin-1 protein level and cholesterol content in crude mitochondrial fraction) in groups of mice divided according to disease progression and training status. The progression of ALS was related to the lowering of Caveolin-1 protein levels and the accumulation of cholesterol in a crude mitochondrial fraction. These changes were associated with aerobic and anaerobic energy metabolism dysfunction and higher oxidative stress. Our data indicated that swim training prolonged the lifespan of ALS mice with accompanying changes in MAM components. Swim training also maintained mitochondrial function and lowered oxidative stress. These data suggest that modification of MAMs might play a crucial role in the exercise-induced deceleration of ALS development

hmSOD1 gene mutation‐induced disturbance in iron metabolism is mediated by impairment of Akt signalling pathway

Abstract Background Recently, skeletal muscle atrophy, impairment of iron metabolism, and insulin signalling have been reported in rats suffering from amyotrophic lateral sclerosis (ALS). However, the interrelationship between these changes has not been studied. We hypothesize that an impaired Akt–FOXO3a signalling pathway triggers changes in the iron metabolism in the muscles of transgenic animals. Methods In the present study, we used transgenic rats bearing the G93A hmSOD1 gene and their non‐transgenic littermates. The study was performed on the muscles taken from animals at three different stages of the disease: asymptomatic (ALS I), the onset of the disease (ALS II), and the terminal stage of the disease (ALS III). In order to study the molecular mechanism of changes in iron metabolism, we used SH‐SY5Y and C2C12 cell lines stably transfected with pcDNA3.1, SOD1 WT and SOD1 G93A, or FOXO3a TM‐ER. Results A significant decrease in P‐Akt level and changes in iron metabolism were observed even in the group of ALS I animals. This was accompanied by an increase in the active form of FOXO3a, up‐regulation of atrogin‐1, and catalase. However, significant muscle atrophy was observed in ALS II animals. An increase in ferritin L and H was accompanied by a rise in PCBP1 and APP protein levels. In SH‐SY5Y cells stably expressing SOD1 or SOD1 G93A, we observed elevated levels of ferritin L and H and non‐haem iron. Interestingly, insulin treatment significantly down‐regulated ferritin L and H proteins in the cell. Conversely, cells transfected with small interfering RNA against Akt 1, 2, 3, respectively, showed a significant increase in the ferritin and FOXO3a levels. In order to assess the role of FOXO3a in the ferritin expression, we constructed a line of SH‐SY5Y cells that expressed a fusion protein made of FOXO3a fused at the C‐terminus with the ligand‐binding domain of the oestrogen receptor (TM‐ER) being activated by 4‐hydroxytamoxifen. Treatment of the cells with 4‐hydroxytamoxifen significantly up‐regulated ferritin L and H proteins level. Conclusions Our data suggest that impairment of insulin signalling and iron metabolism in the skeletal muscle precedes muscle atrophy and is mediated by changes in Akt/FOXO3a signalling pathways

Swim Training Modulates Mouse Skeletal Muscle Energy Metabolism and Ameliorates Reduction in Grip Strength in a Mouse Model of Amyotrophic Lateral Sclerosis

Metabolic reprogramming in skeletal muscles in the human and animal models of amyotrophic lateral sclerosis (ALS) may be an important factor in the diseases progression. We hypothesized that swim training, a modulator of cellular metabolism via changes in muscle bioenergetics and oxidative stress, ameliorates the reduction in muscle strength in ALS mice. In this study, we used transgenic male mice with the G93A human SOD1 mutation B6SJL-Tg (SOD1G93A) 1Gur/J and wild type B6SJL (WT) mice. Mice were subjected to a grip strength test and isolated skeletal muscle mitochondria were used to perform high-resolution respirometry. Moreover, the activities of enzymes involved in the oxidative energy metabolism and total sulfhydryl groups (as an oxidative stress marker) were evaluated in skeletal muscle. ALS reduces muscle strength (−70% between 11 and 15 weeks, p < 0.05), modulates muscle metabolism through lowering citrate synthase (CS) (−30% vs. WT, p = 0.0007) and increasing cytochrome c oxidase and malate dehydrogenase activities, and elevates oxidative stress markers in skeletal muscle. Swim training slows the reduction in muscle strength (−5% between 11 and 15 weeks) and increases CS activity (+26% vs. ALS I, p = 0.0048). Our findings indicate that swim training is a modulator of skeletal muscle energy metabolism with concomitant improvement of skeletal muscle function in ALS mice

Oxidative stress in neurology and in neurodegenerative processes

Aging is one of the principal risk factors that play an important role in several human conditions and pathogenesis, primarily neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD). A progressive loss of neurons, reduced motor or behavioral functions, and abnormally aggregated proteins define these conditions. An unbalanced redox environment, including the generation of excessive reactive oxygen species (ROS) or system deficiency, causes oxidative stress (OS). The brain is one of the principal organs that are particularly susceptible to ROS because of its elevated oxygen demand and the presence of abundant peroxidation-sensitivelipid cells. Previous studies have reported that widespread neurodegenerative disease pathophysiology involves OS. Cellular antioxidants are known to alter such redox status, target destruction, and regulate oxidative mechanisms engaged in cell proliferation, gene expression, signal transduction, and cell death pathway. Oxidants and antioxidants are important in maintaining free balance, metabolized, environmental-related radicals and the body’s antioxidant mechanisms. In biological systems, several complex natural antioxidant mechanisms occur that work together to prevent prooxidant damage. The objective of this chapter is to demonstrate that free radicals are engaged in neurodegenerative disease pathophysiology and that antioxidants and scavenging products help in the prevention and cure of such disease conditions. This chapter also examines the role of antioxidants in neurodegenerative illnesses, in their chemoprevention and therapy