This study was designed to determine the histological and metabolic effects of the administration of 5′-AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) for 14 successive days. AICAR treatment caused a significant decrease in the percentage of type IIB fibers and the concomitant increase in the percentage of type IIX fibers in extensor digitorum longus (EDL) muscle. The capillary density and the capillary-to-fiber ratio were not altered by AICAR. AICAR treatment increased the glycolytic and oxidative enzyme activities but not the antioxidant enzyme activities. The AICAR treatment increased the uncoupling protein 3 (UCP3) level in EDL and the peroxisome proliferator-activated receptor-γ coactivator-1α protein level in the soleus and EDL muscles, whereas the myogenin level was not altered by AICAR. These results seem to imply that the chronic activation of AMPK alters such muscle histochemical and metabolic characteristics.

AMP-activated protein kinase (AMPK), which was activated by an antihyperglycemic drug metformin, has been hypothesized to mediate metabolic adaptations. The purposes of the present study were 1) to confirm whether acute metformin administration induced AMPK phosphorylation and 2) to determine whether chronic metformin treatment increased the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein expression, glycolytic and oxidative enzyme activities, and cytochrome c and glucose transporter-4 (GLUT4) protein expressions in the rat soleus and red and white gastrocnemius muscles. The single oral administration of metformin (300 mg/kg body wt) enhanced the AMPK phosphorylation at 5 and/or 6 h after treatment. In the chronic study, rats were fed either normal chow or chow containing 1% metformin for 14 days. Metformin treatment resulted in a mean daily metformin intake of 631 mg·kg body wt⁻¹·day⁻¹. Metformin increased the PGC-1α content in all three muscles. Metformin increased the hexokinase activity in the white gastrocnemius, the citrate synthase activity in all three muscles, and the β-hydroxyacyl-CoA dehydrogenase activity in the soleus. The cytochrome c protein content in the soleus muscle also increased. The GLUT4 content was unchanged by metformin. These results suggest that metformin enhances the PGC-1α expression and mitochondrial biogenesis possibly at least in part via AMPK phosphorylation in the skeletal muscle. Metformin has thus been proposed to possibly ameliorate insulin resistance, at least partially, by means of such metabolic effects.

In Japan and other developed countries, the lifestyles of many—particularly the younger generation—have been disrupted in recent years. This disruption may manifest as a decrease in physical activity and deterioration in the quality and quantity of sleep. Depressive tendencies are also increasing among university students. This study examined the relationship between mental health, physical activity, physical fitness, and daytime sleepiness. Eighty-five undergraduate students participated in this study (52 men and 33 women, aged 18.9 (±1.4) years). Physical activity levels were measured using an accelerometer (Lifecorder, Kenz, Nagoya, Japan) for two weeks. To evaluate their level of physical fitness, maximal oxygen uptake ($\dot{\mathrm{V}}$O₂max) was calculated by an indirect method using a cycle ergometer. Depressive tendencies and daytime sleepiness were evaluated using the Patient Health Questionnaire (PHQ-9). The PHQ-9 score was positively correlated with sleepiness (r = 0.35, p = 0.001) and total steps per day (r = 0.39, p < 0.001). Moreover, the PHQ-9 score was positively correlated with $\dot{\mathrm{V}}$O₂max (r = 0.25, p = 0.019). The PHQ-9 score was higher in students with good exercise habits or part-time jobs. An important finding was the positive correlation between depression and variables related to physical activity levels. These results suggest that vigorous physical activity, such as exercise and part-time jobs, might be positively associated with depressive tendencies among university students.