Skeletal muscle atrophy is thought to result from hyperactivation of intracellular protein degradation pathways, including autophagy and the ubiquitin-proteasome system. However, the precise contributions of these pathways to muscle atrophy are unclear. Here, we show that an autophagy deficiency in denervated slow-twitch soleus muscles delayed skeletal muscle atrophy, reduced mitochondrial activity, and induced oxidative stress and accumulation of PARK2/Parkin, which participates in mitochondrial quality control (PARK2-mediated mitophagy), in mitochondria. Soleus muscles from denervated Park2 knockout mice also showed resistance to denervation, reduced mitochondrial activities, and increased oxidative stress. In both autophagy-deficient and Park2-deficient soleus muscles, denervation caused the accumulation of polyubiquitinated proteins. Denervation induced proteasomal activation via NFE2L1 nuclear translocation in control mice, whereas it had little effect in autophagy-deficient and Park2-deficient mice. These results suggest that PARK2-mediated mitophagy plays an essential role in the activation of proteasomes during denervation atrophy in slow-twitch muscles.

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These results suggest that muscle type-specific responses occur during endurance exercise, and that the increase in PGC-1alpha expression is not the only factor that promotes oxidative capacity as a result of endurance exercise.

Anorectal function was evaluated in eight patients who had low anterior resection of the rectum with a low anastomotic line, using an EEA stapler, with determination of function based on periodic manometric studies and clinical symptoms. Immediately following surgery all patients suffered from frequent bowel actions and soiling. These symptoms improved with time and most patients could enjoy almost normal daily life by the sixth postoperative month. One month after surgery, anal canal resting pressure and maximum squeeze pressure were significantly reduced and rectoanal inhibitory reflex was absent; neither showed a distinct tendency to improve thereafter. Rectal sensation and reservoir capacity, which also were seriously impaired, recovered satisfactorily by the time of the six-month examination. This suggests that an improvement of clinical symptoms following this operation is dependent upon the recovery of reservoir capacity and sensation of the neorectum, and that this operative procedure is a functionally acceptable option for low rectal cancer.

The prevalence of myopia has been increasing in recent years. The natural carotenoid crocetin has been reported to suppress experimental myopia in mice. We evaluated the effects of crocetin on myopia suppression in children. A multicenter randomized double-blind placebo-controlled clinical trial was performed with 69 participants aged 6 to 12 years, whose cycloplegic spherical equivalent refractions (SER) were between −1.5 and −4.5 diopter (D). The participants were randomized to receive either a placebo or crocetin and followed up for 24 weeks. Axial length (AL) elongation and changes in SER were evaluated for 24 weeks. Both written informed assent from the participants and written informed consent from legal guardians were obtained in this study because the selection criteria of this trial included children aged between 6 and 12 years old. This trial was approved by the institutional review boards. A mixed-effects model was used for analysis, using both eyes. Two participants dropped out and 67 children completed this trial. The change in SER in the placebo group, −0.41 ± 0.05 D (mean ± standard deviation), was significantly more myopic compared to that in the crocetin group, −0.33 ± 0.05 D (p = 0.049). The AL elongation in the placebo group, 0.21 ± 0.02 mm, was significantly bigger than that in the crocetin group, 0.18 ± 0.02 mm (p = 0.046). In conclusion, dietary crocetin may have a suppressive effect on myopia progression in children, but large-scale studies are required in order to confirm this effect.

Aims/Introduction:  Accumulation of intramyocellular lipid (IMCL) is associated with insulin resistance. However, the factors affecting the change in IMCL remain to be elucidated. The aim of the present study was to determine the factors that influence the change in IMCL level after high‐fat loading.Materials and Methods:  The study subjects were 37 non‐obese men. Each subject consumed a high‐fat diet for 3 days after a normal‐fat diet for 3 days. After each diet program, IMCL levels in the tibialis anterior (TA‐IMCL) and soleus (SOL‐IMCL) were measured by proton magnetic resonance spectroscopy. Glucose infusion rate (GIR) was evaluated by euglycemic hyperinsulinemic clamp as an index of peripheral insulin sensitivity.Results:  The high‐fat diet significantly increased TA‐IMCL and SOL‐IMCL by ∼30 and ∼20%, respectively (P < 0.05), whereas it did not significantly alter GIR. The increase in SOL‐IMCL, but not in TA‐IMCL, negatively correlated with serum high molecular weight (HMW)‐adiponectin (r = −0.36, P < 0.05) and HMW‐/total‐adiponectin ratio (r = −0.46, P < 0.05). Although high‐fat diet‐related changes in SOL‐IMCL showed high inter‐individual variations, in subjects doing exercise, changes in SOL‐IMCL (r = 0.55, P < 0.05) and TA‐IMCL (r = 0.61, P < 0.05) positively correlated with daily physical activity level. In contrast, in sedentary subjects, changes in SOL‐IMCL (r = −0.50, P < 0.01) and TA‐IMCL (r = −0.48, P < 0.05) negatively correlated with daily physical activity.Conclusions:  HMW‐adiponectin and daily physical activity are determinants of IMCL accumulation by a high‐fat diet. Intriguingly, the effect of daily physical activity on the change in IMCL depends on the level of regular exercise. (J Diabetes Invest,doi: 10.1111/j.2040‐1124.2010.00091.x, 2011)

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