Niacin supplementation attenuates the regression of three-dimensional capillary architecture in unloaded female rat skeletal muscle.

Inactivity can lead to muscle atrophy and capillary regression in skeletal muscle. Niacin (NA), known for inducing hypermetabolism, may help prevent this capillary regression. In this study involving adult female Sprague-Dawley rats, the animals were randomly assigned to one of four groups: control (CON), hindlimb unloading (HU), NA, and HU with NA supplementation (HU + NA). For a period of 2 weeks, the rats in the HU and HU + NA groups underwent HU, while those in the NA and HU + NA groups received NA (750 mg/kg) twice daily through oral administration. The results demonstrated that HU lowered capillary number, luminal diameter, and capillary volume, as well as decreased succinate dehydrogenase activity, slow fiber composition, and PGC-1α expression within the soleus muscle. However, NA supplementation prevented these alterations in capillary structure due to unloading by stimulating PGC-1α factors and inhibiting mitochondrial dysfunction. Therefore, NA supplementation could serve as a potential therapeutic approach for preserving the capillary network and mitochondrial metabolism of muscle fibers during periods of inactivity.

High Concentrations of Nucleotides Prevent Capillary Regression during Hindlimb Unloading by Inhibiting Oxidative Stress and Enhancing Mitochondrial Metabolism of Soleus Muscles in Rats.

Prolonged inactivity in skeletal muscles decreases muscle capillary development because of an imbalance between pro- and antiangiogenic signals, mitochondrial metabolism disorders, and increased oxidative stress. Nucleotides have been shown to exert a dose-dependent effect on disuse-induced muscle atrophy. However, the dose-dependent effect on capillary regression in disused muscles remains unclear. Therefore, this study investigated the dose-dependent effect of nucleotides on capillary regression due to disuse. For this purpose, Wistar rats were divided into five groups as follows: control rats fed nucleotide-free diets (CON), hindlimb-unloaded rats fed nucleotide-free diets (HU), and hindlimb-unloaded rats fed 1.0%, 2.5%, and 5.0% nucleotide diets, (HU + 1.0% NT), (HU + 2.5% NT), and (HU + 5.0% NT), respectively. Unloading increased reactive oxygen species (ROS) production and decreased mitochondrial enzyme activity, thereby decreasing the number of muscle capillaries. In contrast, 5.0% nucleotide-containing diet prevented increases in ROS production and reductions in the expression levels of NAMPT, PGC-1α, and CPT-1b proteins. Moreover, 5.0% nucleotide-containing diet prevented mitochondrial enzyme activity (such as citrate synthase and beta-hydroxy acyl-CoA dehydrogenase activity) via NAMPT or following PGC-1α upregulation, thereby preventing capillary regression. Therefore, 5.0% nucleotide-containing diet is likely to prevent capillary regression by decreasing oxidative stress and increasing mitochondrial metabolism.

Protective effects of chlorogenic acid on capillary regression caused by disuse muscle atrophy.

Inactivity causes muscle atrophy and capillary regression in skeletal muscle. Chlorogenic acid has an antioxidant capacity and may prevent capillary regression. Therefore, the protective effects of chlorogenic acid on inactivity-induced capillary regression in rat soleus muscle were investigated. Twenty male Wistar rats were randomly divided into four groups: control (CON), chlorogenic acid supplementation (CGA), 2-week hindlimb unloading (HU), 2-week hindlimb unloading plus chlorogenic acid supplementation (HU+CGA). The rats in CGA and HU+CGA groups were orally administrated chlorogenic acid (850 mg/kg/day). Unloading resulted in a decrease in capillary number, oxidative capacity, and an increase in oxidative stress of the soleus muscle, whereas chlorogenic acid supplementation prevented capillary and metabolic changes resulting from unloading by reducing oxidative stress. In conclusion, chlorogenic acid supplementation may qualify as an effective treatment to reduce capillary regression in skeletal muscle caused by disuse muscle atrophy.