Effects of alternate-day fasting on high-fat diet-induced insulin resistance in rat skeletal muscle.

AIMS: The purpose of this study was to investigate the effects of alternate-day fasting (ADF) on insulin-stimulated glucose transport activity in skeletal muscle in rats fed a high-fat diet. MAIN METHODS: Male Wistar rats were placed on a high-fat diet (n=24) or standard chow diet (Chow, n=12) for 10weeks. Rats fed the high-fat diet were separated into two groups after 4weeks. One group was subjected to ADF for the subsequent 6weeks (HF-ADF, n=12), and the other group was maintained on an ad libitum diet (HF-AL, n=12). After the 10-week dietary intervention, measurements of insulin-stimulated glucose uptake and insulin tolerance test (ITT) were performed. KEY FINDINGS: Whereas the total intra-abdominal fat mass in the HF-AL group was significantly higher than in the Chow and HF-ADF groups, there was no significant difference between the Chow and HF-ADF groups. However, insulin-stimulated glucose uptake in skeletal muscles was significantly lower in both high-fat fed groups than in the Chow group. Muscle GLUT-4 protein content in HF-AL is significantly lower (~30%) than in Chow, and further reduction (~42%) was observed in the HF-ADF group rats. The HF-ADF and HF-AL group rats had less reduction in glycemia than did the Chow group rats during ITT. SIGNIFICANCE: ADF was unable to eliminate high-fat diet-induced muscle insulin resistance, despite a substantial decrease in total intra-abdominal fat mass. This might have resulted from a reduction in GLUT-4 protein in both HF-AL and HF-ADF rats compared to the Chow group.

Change in PGC-1α expression in rat skeletal muscle after low-intensity prolonged swimming exercise.

After 6-h low-intensity swimming exercise (LIE), peroxisome proliferator-activated receptor γ coactivator -1α (PGC-1α) in whole and nuclear fractions in rat skeletal muscle was higher than the control rats' muscles up to 18 h after LIE. However, no study has reported change in PGC-1α content after that. Therefore, we measured PGC-1α in whole and nuclear fractions in rat skeletal muscle up to 24 h after LIE. Furthermore, we evaluated change in the mRNA of δ-aminolevulinate synthase (ALAS), a mitochondrial protein, to clarify in which fraction of PGC-1α has a physiological role as a transcriptional coactivator for enhancing the mitochondrial oxidative enzymes after exercise. We measured PGC-1α protein content in whole and nuclear fractions in the epitrochlearis (EPI) muscle of male Sprague-Dawley rats (age: 6 w; body weight: 180-200 g) after LIE by Western-blot analysis. The ALAS mRNA content was quantified by RT-PCR. The PGC-1α contents in whole fractions in the rat EPI muscle were 73% and 75% higher than that of the control rats' muscle, 18 h and 24 h after LIE, respectively. The PGC-1α content in nuclear fractions in the muscle and ALAS mRNA was higher than that of the control rats' muscle by 58% and 25%, respectively, while they returned to the control level 24 h after LIE. The present investigation demonstrated that the time-course of PGC-1α content in nuclear fractions in the EPI muscle was the same as the ALAS mRNA, suggesting that PGC-1α in the nucleus may have a physiological function as a transcriptional coactivator for enhancing mitochondrial protein expression after exercise.

A DIGE proteomic analysis for high-intensity exercise-trained rat skeletal muscle.

Exercise training induces various adaptations in skeletal muscles. However, the mechanisms remain unclear. In this study, we conducted 2D-DIGE proteomic analysis, which has not yet been used for elucidating adaptations of skeletal muscle after high-intensity exercise training (HIT). For 5 days, rats performed HIT, which consisted of 14 20-s swimming exercise bouts carrying a weight (14% of the body weight), and 10-s pause between bouts. The 2D-DIGE analysis was conducted on epitrochlearis muscles excised 18 h after the final training exercise. Proteomic profiling revealed that out of 800 detected and matched spots, 13 proteins exhibited changed expression by HIT compared with sedentary rats. All proteins were identified by MALDI-TOF/MS. Furthermore, using western immunoblot analyses, significantly changed expressions of NDUFS1 and parvalbumin (PV) were validated in relation to HIT. In conclusion, the proteomic 2D-DIGE analysis following HIT-identified expressions of NDUFS1 and PV, previously unknown to have functions related to exercise-training adaptations.

Effects of nonexhaustive bouts of high-intensity intermittent swimming training on GLUT-4 expression in rat skeletal muscle.

We previously reported that 14 bouts of exhaustive high-intensity intermittent training [20 s periods of swimming while carrying a weight (14% of body weight), separated by pauses of 10 s] is the highest stimuli in terms of exercise training-induced glucose transporter 4 (GLUT-4) expression in rat epitrochlearis (EPI) muscles. In the present study, we found that the GLUT-4 protein content in the skeletal muscle of male Sprague-Dawley rats (age 5 weeks old; body weight 90-110 g) that underwent intermittent exercise training of 3 and 14 bouts of 20 s swimming for 5 days was increased over age-matched sedentary control rats by 75 and 71%, respectively, 18 h after the last bout of exercise. These results suggest that GLUT-4 content in rat EPI muscle increases dramatically after very short (60 s) and nonexhaustive high-intensity intermittent exercise training.

Effect of running training on DMH-induced aberrant crypt foci in rat colon.

PURPOSE: We examined the effects of treadmill-running training on the induction of aberrant crypt foci (ACF), which is the first step of colon cancer induction, in the colonic mucosa of rats injected with 1,2-dimethylhydrazine (DMH). METHODS: Four-week-old F344 rats (N = 38) were randomly assigned to training (19 rats) and control (19 rats) groups. After a week, all rats were given DMH (20 mg.kg(-1) body weight) once a week for 2 wk. Running training was started at age 7 wk (speed: 10 m.min(-1), 0% grade, 120 min.d(-1), 5 d.wk(-1)). After 4 wk of training, the rats were sacrificed and the colon was removed, opened, and counted for ACF with 0.2% methylene blue staining. RESULTS: Running training resulted in lower body- (P < 0.01) and adipose fat weight (P < 0.05). The numbers of ACF and total AC were significantly lower in the running training group than in the control group (P < 0.05). The occurrences of one, three, and five aberrant crypts per focus were also significantly lower in the running training group than in the control group (P < 0.05). The ratios of total AC/ACF did not significantly differ between the running training and control groups. CONCLUSIONS: The results of the present investigation suggest that low-intensity running training inhibits the DMH-induced initiation of colon ACF development.