Masataka Suwa

Endurance exercise increases the SIRT1 and peroxisome proliferator-activated receptor γ coactivator-1α protein expressions in rat skeletal muscle

Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) is considered to play a pivotal role in the exercise-induced metabolic adaptation of skeletal muscle. Although the oxidized form of nicotinamide adenine dinucloetide (NAD(+))-dependent histone deacetylase SIRT1 has been shown to mediate PGC-1alpha-induced metabolic adaptation, the effect of endurance exercise on the SIRT1 protein remains to be elucidated. The purposes of this study were (1) to investigate the distribution of SIRT1 and PGC-1alpha proteins in skeletal muscle and (2) to examine the effects of acute endurance exercise and low- or high-intensity exercise training on SIRT1 and PGC-1alpha protein expressions and on the metabolic components in rat skeletal muscle. Both the SIRT1 and PGC-1alpha proteins preferentially accumulate in red oxidative muscles. Acute endurance exercise on a motor-driven treadmill (20 m/min, 18.5% incline, 45 minutes) increases the PGC-1alpha protein expression at 18 hours after exercise and the SIRT1 protein expression at 2 hours after exercise in the soleus muscle. In the training experiment, the rats were divided into control, low-intensity (20 m/min, 18.5% incline, 90 min/d), and high-intensity (30 m/min, 18.5% incline, 60 min/d) training groups. After 14 days of training, the SIRT1 and PGC-1alpha proteins, hexokinase activity, mitochondrial proteins and enzyme activities, and glucose transporter 4 protein in the soleus muscle were increased by both trainings. In the plantaris muscle, SIRT1, hexokinase activity, mitochondrial proteins and enzyme activities, and glucose transporter 4 were increased by high-intensity training whereas the PGC-1alpha was not. These results suggest that endurance exercise increases the skeletal muscle SIRT1 protein content. In addition, the findings also raise the possibility that the SIRT1 protein expression may play a potentially important role in such adaptations, whereas an increase in the PGC-1alpha protein expression is not necessary for such adaptations.

Decreased serum brain-derived neurotrophic factor in trained men

The purpose of this study was to clarify the effect of physical activity on the level of serum brain-derived neurotrophic factor (BDNF). The serum BDNF level in trained men who have participated in regular sport activity (n=12) was compared to that in sedentary subjects (n=14). The physical activity levels expressed as total energy expenditure, move-related energy expenditure and walking count in the trained were significantly higher than those in the sedentary. The serum BDNF level in the trained men was found to be lower than that in the sedentary (19.54+/-4.53 ng/ml vs. 23.63+/-2.94 ng/ml, respectively, P<0.01). The serum BDNF level showed a significant negative correlation with daily total energy expenditure (r=-0.507, P<0.05), movement-related energy expenditure (r=-0.503, P<0.05), and walking count (r=-0.480, P<0.05). These results may suggest that vigorous habitual physical activity decrease the serum BDNF level.

Short-term adenosine monophosphate–activated protein kinase activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside treatment increases the sirtuin 1 protein expression in skeletal muscle

Adenosine monophosphate-activated protein kinase (AMPK) has been proposed to stimulate mitochondrial biogenesis and fat and glucose metabolism in skeletal muscle. Nicotinamide adenine dinucleotide-dependent histone deacetylase sirtuin 1 (SIRT1) is also thought to play a pivotal role for such metabolic adaptations. The purpose of the present study was to examine the effect of AMPK activation with the administration of AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) to rats on skeletal muscle SIRT1 protein expression as well as peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α) and glucose transporter 4 (GLUT4) protein expression and hexokinase activity. The AICAR promoted the phosphorylation of AMPK α-subunit (Thr¹⁷²) and acetyl-coenzyme A carboxylase (Ser⁷⁹) without any change of total AMPK α-subunit or acetyl-coenzyme A carboxylase protein levels in both the slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles. The SIRT1 protein expression increased at 24 hours after administration of AICAR in the EDL muscle but not in the soleus muscle. The PGC-1α protein expression increased in both the soleus and EDL muscles and GLUT4 did in the EDL muscle at 24 hours after an administration of AICAR. The hexokinase activity increased at 18 and 24 hours in the soleus and at 12, 18, and 24 hours in the EDL after an AICAR treatment. These results suggest that short-term AICAR treatment to rats promotes skeletal muscle AMPK phosphorylation and then coincidently increases the SIRT1 protein expression. In addition, such treatment also enhances the PGC-1α and GLUT4 protein contents and hexokinase activity in skeletal muscle.

Dietary obesity-resistance and muscle oxidative enzyme activities of the fast-twitch fibre dominant rat

Objectives: To clarify whether the muscle fibre composition and/or muscle oxidative enzyme activity are related to dietary body weight gain and abdominal fat accumulation.Methods: Genetically fast-twitch fibre dominant rats (FFDR) and control rats (CR) were divided into low-fat (20% of energy from fat) or high-fat (60% of energy from fat) diet groups: CR with a low-fat diet (CL); CR with a high-fat diet (CH); FFDR with a low-fat diet (FL); and FFDR with a high-fat diet (FH). After 6 weeks of following such diets, the body weight gain, abdominal fat content, food intake, muscle fibre composition and oxidative enzyme activities were estimated.Results: The total body weight gain in CH was from 18 to 62% higher than in the other groups (P<0.05) and percentage abdominal fat in CH was also from 26 to 61% higher than in the other groups (P<0.05), while the energy intake did not differ among the groups. The percentage of type IIX fibres of M. gastrocnemius in FL (33.4%) and FH (36.3%) were higher than in CL (16.8%) and CH (19.8%; P<0.05), and the type IIA fibres of M. soleus in FL (14.1%) and FH (11.8%) were higher than in CL (2.0%) and CH (3.5%; P<0.05). The citrate synthase (CS) activity of of M. plantaris in FL and FH were higher than CL (46 and 54%, respectively, P<0.05). β-Hydroxyacyl CoA dehydrogenase (HAD) activity in FL and FH were higher than in CL (21 and 31%, respectively, P<0.05) and that in FH was higher than CH (23%, P<0.05). On the other hand, the enzyme activities of M. gastrocnemius and soleus were identical among the groups.Conclusion: The FFDR was more obesity-resistant than the CR after a high-fat diet. These results suggest that the muscle oxidative capacity rather than muscle fibre composition is a possible determinant of obesity.

The potential role of sirtuins regarding the effects of exercise on aging- related diseases.

Habitual physical activity and exercise are associated with the mortality rate and significantly contribute to the prevention and/or amelioration of aging-related diseases including metabolic disorders, atherosclerosis, cancer, and dementia. Sirtuins are NAD+-dependent histone deacetylases that have emerged as key regulators of many functions including metabolism, cell growth and apoptosis, as well as control of the aging process. Recent studies have demonstrated that some types of exercise affect the expression and activity of sirtuins in several tissues. This review focuses on the effects of exercise on sirtuins and also their putative role with regard to the effects of exercise on preventing aging- related diseases.

Inhibition of calcineurin increases monocarboxylate transporters 1 and 4 protein and glycolytic enzyme activities in rat soleus muscle

1. The present study was designed to examine the role of calcineurin in muscle metabolic components by the administration of the specific calcineurin inhibitor cyclosporine A (CsA) to rats.