Ogasawara R, Kobayashi K, Tsutaki A, Lee K, Abe T, Fujita S, Nakazato K, Ishii N. mTOR signaling response to resistance exercise is altered by chronic resistance training and detraining in skeletal muscle.

This study investigated the injured region-specific alterations of factors related to the "repeated bout effect" (RBE), i.e., when the first bout of eccentric exercise generates resistance to injuries from the second bout of the same exercise. Wistar rats were divided into single injury (SI) and repeated injury (RI) groups. The right gastrocnemius muscle was subjected to a bout of eccentric contractions (ECs) at the age of 14 weeks in the SI group and 10 and 14 weeks in the RI group. The number of injured fibers after the last bout of ECs was lower in RI than in SI. In the SI group, injured fibers after ECs were mainly located in the superficial region of muscle and expressed myosin heavy chain (MHC) IIx and IIb. Prior to the second bout of ECs, the fiber-type composition in the RI group showed decreased MHC IIx and IIb fibers and increased MHC IIa fibers compared with those in the SI group. However, most regenerating fibers showed either MHC IIx or IIb expression. Heat shock protein 72 and total collagen contents in whole muscle were higher in the RI group than in the SI group; however, only the collagen expression in the RI group was more intense than that in the SI group in the superficial region of muscle. These findings suggest that increased collagen may play a more important role in the injured region of muscle than the other factors in RBE.

ECs with fast angular velocities induce functional and structural damage in innervating nerve.

The recovery period between bouts of exercise is one of the major factors influencing the effects of resistance exercise, in addition to exercise intensity and volume. However, the effects of shortening the recovery time between bouts of resistance exercise on subsequent protein synthesis remain unclear. In this study, we investigated the consequences of shortening the recovery time between bouts of resistance exercise on protein synthesis and related processes in mouse skeletal muscles. Eighteen male C57BL/6J mice were randomly subjected to three bouts of resistance exercise with 72 (72H), 24 (24H), or 8 h (8H) of recovery periods between bouts. Resistance exercise, consisting of five sets of 3 s × 10 isometric contractions with 3 min rest between sets, was elicited on the right tibialis anterior muscle via percutaneous electrical stimulation on the deep peroneal nerve under isoflurane anesthesia. The left muscle served as an internal control. Six hours after the third bout of exercise, protein synthesis was found to be activated in the 72H and 24H groups, but not in the 8H group. Phosphorylation of p70S6K at Thr 389, a marker of mammalian target of rapamycin (mTOR) signaling, was increased in all groups, with the 8H group showing the highest magnitude. In contrast, protein carbonylation was observed only in mice in the 8H group. These results suggest that repeated bouts of resistance exercise with 8 h of recovery periods do not effectively increase the levels of muscle protein synthesis despite activation of the mTOR signaling pathway, which likely involves oxidative stress.

Low-frequency neuromuscular electrical stimulation (NMES) has been used as an endurance exercise model. This study aimed to test whether low-frequency NMES increases the phosphorylation of anabolic signaling molecules and induces skeletal muscle hypertrophy, as seen with high-frequency NMES. Using Sprague-Dawley rats, 1 bout of exercise (with dissection done immediately (Post0) and 3 h (Post3) after exercise) and another 6 sessions of training were performed. All experimental groups consisted of high- and low-frequency stimulation (HFS: 100 Hz; LFS: 10 Hz). Periodic acid-Schiff (PAS) staining was conducted to investigate type II fiber activation, and western blot analysis (WB) was conducted to examine whether NMES leads to anabolic intracellular signaling. At first, we examined the acute effect of exercise. PAS staining revealed that glycogen depletion occurred in both type I and type II fibers. WB results demonstrated that p70S6K phosphorylation was significantly increased by HFS, but there was no significant difference with LFS. In contrast, ERK 1/2 phosphorylation was increased by LFS at Post0. In the 6-session training, the wet weight and myofibrillar protein were significantly increased by both HFS and LFS. In conclusion, LFS has a similar anabolic effect for skeletal muscle hypertrophy as HFS, but the mediating signaling pathway might differ.

No abstract

In this review, we briefly summarize muscle fiber types and mechanisms that regulate their expression from nutritional stimulus. To begin with, we introduce genes and their location on myosin heavy chains (MyHC). Next, we show three major transcriptional controls for MyHCs as (1) calcium signaling, (2) AMPK signaling, and (3) miRNA/anti-sense RNA regulations. Following this, we summarize possible nutrients that effect muscle fiber type transformation. The possible contributors are caloric restriction, polyphenols, and high-fat and high-protein diets. We think that nutritional intervention will be a useful way to control muscle fiber type switching. This approach could be adopted by athletes as a means to condition their muscles.

High-intensity exercise has recently been shown to cause an increase in brain-derived neurotropic factor (BDNF) in the hippocampus. Some studies have suggested that myokines secreted from contracting skeletal muscle, such as irisin (one of the truncated form of fibronectin type III domain-containing protein 5 (FNDC5)), play important roles in this process. Thus, we hypothesized that locally evoked muscle contractions may cause an increase of BDNF in the hippocampus through some afferent mechanisms. Under anesthesia, Sprague-Dawley rats were fixed on a custom-made dynamometer and their triceps surae muscles were made to maximally contract via delivery of electric stimulations of the sciatic nerve (100 Hz with 1-ms pulse and 3-s duration). Following 50 repeated maximal isometric contractions, the protein expressions of BDNF and activation of its receptor in the hippocampus significantly increased compared with the sham-operated control rats. However, the expression of both BDNF and FNDC5 within stimulated muscles did not significantly increase, nor did their serum concentrations change. These results indicate that local muscular contractions under unconsciousness can induce BDNF expression in the hippocampus. This effect may be mediated by peripheral reception of muscle contraction, but not by systemic factors.