New Findings r What is the central question of this study?We asked whether the combination of astaxanthin supplementation and intermittent loading would attenuate both the muscle atrophy and the capillary regression associated with chronic unloading. r What is the main finding and its importance?Intermittent loading alone attenuated atrophy of the soleus, while astaxanthin treatment alone maintained the capillary network in the soleus. The combination of these two interventions ameliorated both the muscle atrophy and the capillary regression induced by chronic unloading.A chronic decrease in neuromuscular activity (activation and/or loading) results in muscle atrophy and capillary regression that are due, in part, to the overproduction of reactive oxygen species. We have reported that antioxidant treatment with astaxanthin attenuates the overexpression of reactive oxygen species in atrophied muscles that, in turn, ameliorates capillary regression in hindlimb-unloaded rats. Astaxanthin supplementation, however, had little effect on muscle mass and fibre cross-sectional area. In contrast, intermittent loading of the hindlimbs of hindlimb-unloaded rats ameliorates muscle atrophy. Therefore, we hypothesized that the combination of astaxanthin supplementation and intermittent loading would attenuate both muscle atrophy and capillary regression during hindlimb unloading. As expected, 2 weeks of hindlimb unloading resulted in atrophy, a decrease in capillary volume and a shift towards smaller-diameter capillaries in the soleus muscle. Intermittent loading alone (1 h of cage ambulation per day) attenuated atrophy of the soleus, while astaxanthin treatment alone maintained the capillary network to near control levels. The combination of intermittent loading and astaxanthin treatment, however, ameliorated atrophy of the soleus and maintained the capillary volume and luminal diameters and the superoxide dismutase-1 protein levels near control values. These results indicate that intermittent loading combined with astaxanthin

These results suggest that astaxanthin may be an effective treatment to counter the detrimental effects of a chronic decrease in skeletal muscle use on the capillary network and associated angiogenic pathways.

Aim: Data on the skeletal muscle characteristics of patients and animals with lifestyle-related diseases are limited. We investigated mRNA expression levels and fiber profiles in the skeletal muscles of rats with obesity, diabetes, hypertension, and/or hyperlipidemia. Methods: The mRNA expression levels of peroxisome proliferator-activated receptors (PPAR and PPAR / ), PPAR coactivator-1 (PGC-1 ), stearoyl-CoA desaturase-1 (SCD-1), carnitine palmitoyl-transferase (CPT ), medium-chain acyl-CoA dehydrogenase (MCAD), and mitochondrial transcriptional factor A (TFAM) in the soleus muscles were compared among 15-week-old control (WR), type 2 diabetic (GK), hypertensive (SHR), and hyperlipidemic (CP) rats. The fiber profiles in the soleus muscles of these rats were also determined. Results: GK rats showed lower PPAR / , PGC-1 , and MCAD expression levels than WR rats. SHR rats showed higher PPAR and MCAD and lower PPAR / expression levels than WR rats. CP rats showed lower PPAR / and higher SCD-1 expression levels than WR rats. The muscles of WR, SHR, and CP rats had low-oxidative type and high-oxidative type A and type C fibers, whereas the muscle of GK rats had only low-oxidative type fibers. Conclusions:The skeletal muscles of rats with lifestyle-related diseases have unique mRNA expression patterns and fiber profiles depending on the type of disease. For example, the lower PGC-1 and MCAD mRNA expression levels in the soleus muscles of type 2 diabetic rats are associated with the presence of only low-oxidative type fibers in the muscle. J Atheroscler Thromb, 2009; 16:576-585.Key words; Lifestyle-related disease, mRNA expression level, Muscle fiber type bility of ATPase at acidic pH. Type A fibers become ATPase negative at a faster rate than type B fibers when the acidity of the preincubation medium increases. Type C fibers have been identified in skeletal muscles, particularly in the soleus muscle of rats; these fibers are ATPase positive, irrespective of the pH of the preincubation medium. Glycolytic enzyme activity is higher in type A, type B, and type C fibers than in type fibers, whereas oxidative enzyme activity is higher in type , type A, and type C fibers than in type B fibers; therefore, the presence of different types of fibers correlates with the metabolic properties of individual skeletal muscles. Skeletal muscles exhibit plasticity and undergo fiber type transitions under various conditions, such as growth, aging,

We examined the fiber profiles and the mRNA levels of peroxisome proliferator-activated receptors (PPARα and PPARδ/β) and of the PPARγ coactivator-1α (PGC-1α) in the plantaris muscles of 15-week-old control (WR), metabolic syndrome (CP), hypertensive (SHR), and type 2 diabetic (GK) rats. The deep regions in the muscles of SHR and GK rats exhibited lower percentages of high-oxidative type I and IIA fibers and higher percentages of low-oxidative type IIB fibers compared with WR and CP rats. The surface regions in the muscles of CP, SHR, and GK rats exhibited lower percentages of high-oxidative type IIA fibers and higher percentages of low-oxidative type IIB fibers compared with WR rats. The muscles of SHR and GK rats had lower oxidative enzyme activity compared with WR rats. The muscles of SHR rats had the lowest PPARδ/β mRNA level. In addition, the muscles of SHR and GK rats had lower PGC-1α mRNA level compared with WR and CP rats. We concluded that the plantaris muscles of rats with hypertension and type 2 diabetes have lower oxidative capacity, which is associated with the decreased level of PGC-1α mRNA.

Combined, the results indicate that low-intensity exercise reduces some of the microcirculatory complications in type 2 diabetic muscles.