Effects of AICAR Treatment on Muscular, Cardiorespiratory, and Hsp25 Adaptations to Treadmill versus Running Wheel Exercise Training in Mice
FASEB JOURNAL(2018)
Abstract
AMPK agonists, such as AICAR, are used in the treatment of diabetes since they mimic several effects of exercise such as a more oxidative phenotype and increased insulin sensitivity. Exercise training can increase muscle levels of heat shock protein 25 (Hsp25), which is associated with improvements in muscle function and insulin‐stimulated glucose uptake. In contrast decreased Hsp25 in skeletal muscle is associated with insulin resistance in rats. Evidence in animals and humans suggests the combination of exercise and AMPK‐activating drugs may decrease exercise‐training adaptations. These experiments compared the effects of AICAR on cardiorespiratory, muscular, and Hsp25 adaptations to forced (treadmill, TM) or voluntary (running wheel, RW) training. It was hypothesized that AICAR + TM or RW would attenuate increases in exercise capacity, muscle force, and Hsp25 expression compared to training alone. Adult, male C57 mice were divided into 6 groups (n = 8–10/group): 1‐Placebo, 2‐AICAR, 3‐Placebo + TM, 4‐Aicar + TM, 5‐Placebo + RW, 6‐Aicar + RW. Groups received daily placebo or AICAR with or without TM or RW over 7 days. Plantarflexor muscle force and fatigue (% of max force after 10 contractions) were measured in vivo and exercise capacity was assessed with pre‐ and post‐ treadmill tests. Muscle Hsp25 protein levels were quantified with western blot. AICAR significantly reduced average daily RW distance vs. placebo, 1099±133 and 1923±103 m/day, respectively. AICAR + TM did not affect training‐associated increases in exercise capacity compared to Placebo + TM (Δ time pre to post: 903 ± 164 vs. 1,188 ± 99 sec. for AICAR and Placebo, respectively, p<0.05); however, AICAR + RW attenuated the increases in exercise capacity compared to Placebo + RW (Δ time pre to post: 710 ± 134 vs. 921 ± 87 sec. for AICAR and Placebo, respectively, p<0.05). Muscle force was increased with AICAR in TM or sedentary groups compared to placebo while AICAR + RW was associated with reduced muscle force compared to Placebo + RW (Placebo: 1.2 ± 0.07 vs. 1.3 ± 0.07 vs. 1.4 ± 0.08 and AICAR: 1.4 ± 0.08 vs. 1.5 ± 0.12 vs. 1.1± 0.11 g/g body mass, for sedentary, TM, and RW, respectively, p<0.05). Fatigability was greater with AICAR in sedentary mice; however, AICAR + TM decreased fatigability compared to AICAR alone (p<0.05). TM or RW increased Hsp25 levels in both placebo and AICAR groups compared to sedentary placebo (Placebo: 0.09 ± 0.01 vs. 0.15 ± 0.01 vs. 0.15 ± 0.02 and AICAR 0.15 ± 0.02 vs. 0.17 ±0.02 vs. 0.19 ± 0.03 AU, for sedentary, TM, and RW, respectively, p<0.05) and AICAR increased Hsp25 in the sedentary group compared to placebo (0.15 ± 0.02 vs. 0.09 ± 0.01 AU, p<0.05). These findings suggest AICAR does not impair cardiorespiratory or muscular adaptations to forced exercise while AICAR reduced RW distance and training associated adaptations to voluntary exercise. AICAR in combination with forced or voluntary exercise did not impair Hsp25 increases and AICAR alone mimics exercise induced Hsp up‐regulation in sedentary muscle and may be one mechanism whereby AICAR and/or exercise improve outcomes with diabetes. Support or Funding Information APS UGSRF to KG This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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Key words
running wheel exercise training,treadmill,aicar treatment,hsp25 adaptations,cardiorespiratory
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