The impact of muscle inactivity and exercise training on histidine dipeptide homeostasis in rat skeletal muscle

Evidence suggests that muscle activity can affect muscle carnosine, but the results are mixed. To address this question, we investigated muscle carnosine under the two extremes of the muscle activity-inactivity spectrum. Forty-five male Wistar rats were divided into 3 groups: immobilisation ( n=16), SHAM control ( n=14), and immobilisation+exercise ( n=15). In the immobilised groups, one side was submitted to a sciatic nerve sectioning surgery, with the opposite side being submitted to a SHAM control surgery, creating 4 experimental conditions: denervated (DEN), SHAM active control (SHAM), denervated+exercise (DEN+Ex), and SHAM+exercise (SHAM+Ex). The immobilisation period was 12 weeks, and the swimming training period was 10 weeks (4 times per week, up to 30 min per session). The tibialis anterior (TA) and soleus muscles from both sides were assessed for carnosine and anserine content, total histidine-dipeptides (HCDs), cross-sectional fibre area (CSA) and fibre type distribution. Contractile function was determined ex-vivo in the extensor digitorum longus and the expression of the Carns1, Cndp2 and TauT genes was determined with real-time PCR in TA. Physical inactivity reduced drastically muscle mass, contractile function, and fibre CSA. Long-term post-denervation muscle paralysis reduced muscle carnosine and anserine content, which was not dependent on diet, age, sex or fibre-type. This demonstrates that muscle inactivity is a strong modulator of muscle HCDs content, at least under extreme conditions. Gene expression was not significantly altered in any of the experimental conditions. Exercise training, on the other hand, did not affect muscle HCDs, and may be a less potent regulator of muscle HCDs content.