SUBSTRATE REGULATION BY SKELETAL MUSCLE AFTER HINDLIMB SUSPENSION

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The extended limb unloading during space travel may diminish functional capacity such that mission safety and effectiveness are compromised. The hindlimb suspension model of limb unloading alters both biochemical and contractile characteristics of skeletal muscle causing atrophy and type I to type II conversion of muscle fibers. In contrast, exercise training induces alterations in the biochemical, but not contractile, characteristics of skeletal muscle, primarily an increased capacity to use fat as a substrate during exercise. The experiments in this project will differentiate between the consequences of intrinsic muscle fiber type conversion and the biochemical adaptations to normal exercise training. Preliminary experiments were conducted in the rat using infusions of [3-13C]lactate and [1,2-13C]acetate during rest, exercise, and exercise following glycogen depletion. We found that in the gastrocnemius (a type II muscle), incorporation of [3-13C]lactate into the TCA cycle increased from 15.7% to 24.8% and 45.9% during rest, after control exercise, and after exercise with glycogen depletion. At the same time, incorporation of [1,2-13C]acetate declined from 54.4% to 39.7% and 30.9%. Anaplerosis of the TCA cycle was proportional to exercise time. In contrast, the soleus (a type I muscle) took up a greater fraction of [1,2-13C]acetate and a lower fraction of [3-13C]lactate, with no detectable TCA cycle anaplerosis. This great difference between the soleus and the gastrocnemius provides a sensitive indicator of the metabolic consequences of any fiber type conversions induced by hindlimb suspension, and the efficacy of exercise training to partially attenuate the effects of fiber type conversion. (Service 7) REPORT PERIOD: (09/01/97-08/31/98)