Changes in protein turnover in skeletal muscle in response to fasting

In response to a 72-hr fast, rats weighing approximately 220 g initially exhibited a 28% reduction in total body weight and a 25% reduction in the weight of the gastrocnemius muscle. Reduced muscle weight was paralleled by a reduction in muscle protein, which, as determined in the perfused hemicorpus preparation, was the result of a 50% decrease in the rate of protein synthesis and an unchanged rate of protein degradation. During the first 24 hr of fasting, a decrease in the level of plasma insulin was associated with a block in peptide-chain initiation and a reduction in the efficiency of protein synthesis. Longer periods of fasting caused a decrease in the level of muscle RNA and a loss of protein synthetic capacity. Perfusion of muscle in the presence of insulin completely removed the block in peptide-chain initiation, restoring the efficiency of synthesis to normal, whereas the capacity of synthesis was unchanged. Although protein degradation in the 220-g rats was not altered by food deprivation, the degradative rate of 100-g rats fasted for 48 hr was 30-50% greater than that observed in fed controls. The increased rate of degradation in these preparations was accompanied by an increase in the specific activity of a lysosomal protease, cathepsin D. Although addition of insulin lowered the rate of protein degradation in the perfused muscle preparation under all conditions tested, the increase in degradation in the fasted, 100-g rats could not be explained solely on the basis of acute insulin deficiency.