Since unloading conditions stimulate the ubiquitination of muscle proteins, we comprehensively examined the types of ubiquitin ligases that are activated by unloading. We found that unloading stress resulted in skeletal muscle atrophy through induction and activation of the ubiquitin ligase Cbl-b. Upon induction, Cbl-b interacted with and degraded the IGF-1 signaling intermediate, IRS-1. In turn, the loss of IRS-1 activated the FOXO3-dependent induction of atrogin-1/MAFbx, a dominant mediator of proteolysis in atrophic muscle. Cbl-b-deficient mice were resistant to unloading-induced atrophy and the resulting loss of muscle function. A DG (p) YMP pentapeptide mimetic of tyrosine608-phosphorylated IRS-1, named Cblin (Cbl-b inhibitor) , inhibited Cbl-b-mediated IRS-1 ubiquitination and strongly decreased the Cbl-b-mediated induction of atrogin-1/MAFbx. Furthermore, we also found a Cblin-like peptide in soy glicinine that similarly inhibited the IRS-1 ubiquitination and skeletal muscle volume loss caused by denervation in vitro and in vivo. In particular, a soy protein isolate-supplemented diet increased the extension power of the knee in bedridden patients. Our results indicate that Cbl-b-dependent destruction of IR-1 is a critical dual mediator of both increased protein degradation and reduced protein synthesis observed in unloading-induced muscle atrophy. Inhibition of Cbl-b-mediated ubiquitination may be a new therapeutic strategy for unloading-mediated muscle atrophy.
The present study was conducted to compare bone mineral density (BMD) among long distance runners with sprinters, and to examine factors related to BMD at different bone sites among female high school track and field athletes. Thirty-seven adolescent female long distance runners (LDRs) and sprinters (SPRs) (16.1±0.8 yr old, LDR ［＞800 m］ n＝16, SPR ［100‐400 m］ n＝21) participated. We measured BMD and fat-free mass (FFM) by DXA. In addition, we assessed nutrient intake, physical activity, prior history of stress fracture and menstrual state using a questionnaire. BMD and FFM were significantly higher in SPRs than in LDRs. Multiple regression analysis showed that FFM was a significant covariate of BMD at all sites except for the spine. Seafood intake was a significant covariate of BMD in the arms, pelvis and total bone less head (TBLH) . BMI was a significant covariate of BMD in the pelvis. Differences in BMD between LDRs and SPRs were strongly influenced by FFM, and seafood intake was shown to be a factor contributing significantly to BMD among female high school track and field athletes.
On the basis of data from beverage consumption surveys (1996‐2013) , we previously reported that polyphenol intake from beverages was high in the winter and low in the summer. Although it is well known that the Japanese diet varies with the seasons, seasonal variations in polyphenol intake from foods remain unclear. Here, we calculated the polyphenol intake from vegetables and fruits in each month of the year using data from the Family Income and Expenditure Survey (2015) and our polyphenol content database. There were small variations in polyphenol intake from fresh vegetables among the seasons. Polyphenol intake from fresh fruits was lowest in the summer and highest in the winter, especially in December. Variations in the polyphenol content of fruits widely consumed in each month accounted for the seasonal differences. Our results suggest that polyphenol intake from vegetables and fruits is slightly influenced by seasonal changes in food consumption, and that total polyphenol intake might be low in summer.
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