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Disruption of Adenylyl Cyclase Type 5 Mimics Exercise Training
Author(s) -
Zhang Jie,
Keim Catharine,
Lai Lo,
Yan Lin,
Vatner Stephen F.,
Vatner Dorothy E
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1240.21
Subject(s) - adenylyl cyclase , endocrinology , skeletal muscle , medicine , knockout mouse , physical exercise , stimulation , receptor
Adenylyl cyclase type 5 knockout mice (AC5 KO) exhibit enhanced exercise compared to their wild type (WT) littermates and also have enhanced mitochondrial function. Enhanced exercise performance, mediated in part by increased mitochondrial function, is also a feature of exercise training. Accordingly, the goal of this investigation was to compare mechanisms mediating the improved exercise in AC5 KO with that of exercise training in their WT littermates. To accomplish this, we compared genes up or down regulated in the two models using deep sequencing techniques. We also examined the phenotype of the skeletal muscle of AC5 KO to determine if it resembled exercise trained skeletal muscle. Exercise performance, measured by maximal distance, was increased in AC5 KO (n=6) by 32±9%, p<0.01, above levels in WT (449±39m, n=7). Similar significant increases were observed in maximal speed and work to exhaustion in AC5 KO. Chronic exercise training (1 hour of exercise training every day for one month) increased performance in WT (n=7), e.g., distance rose to 569±14m, similar to levels in AC5 KO without training. Chronic exercise training in AC5 KO mice (n=6) increased their performance further, as distance rose to 850±60m. However, a second month of exercise training did not increase WT performance significantly more. The next goal was to determine mechanisms. AC5 KO and trained WT mice shared similar gene expression in their gastrocnemius muscle with 183 genes commonly up‐ or down‐regulated. Shared gene ontology (GO) terms included important muscle regulatory gene sets including those involved in muscle contraction, metabolism, contractile fibers, and mitochondria. Both groups also had similar increases in oxidative fiber content in their gastrocnemius and extensor digitorum longus (EDL) muscle, indicating a fiber‐type switch in the exercising skeletal muscle. AC5 KO and trained WT mice both revealed increased SIRT1 protein levels in the gastrocnemius muscle and protection against oxidative stress. These results suggest that AC5 KO mice, without exercise training, perform better than even WT with exercise training and share similar mechanisms responsible for enhanced exercise capacity, and demonstrate considerably more reserve, allowing further improvement of performance with exercise training.