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LAREW, K., G. R. HUNTER, D. E. LARSON-MEYER, B. R. NEWCOMER, J. P. MCCARTHY, and R. L. WEINSIER. Muscle Metabolic Function, Exercise Performance, and Weight Gain. Med. Sci. Sports Exerc., Vol. 35, No. 2, pp. 230–236, 2003.The study purpose was to determine the relationship: 1) of muscle metabolism to exercise performance and 2) of exercise performance to rate of weight gain. Eighty-three black and white premenopausal women were evaluated for maximum oxygen uptake (V̇O2max), isometric quadriceps and triceps surae strength, and 31P magnetic resonance spectroscopy of calf muscle metabolic capacity. Rate of weight gain was determined 1 yr later. Multiple regression was used to model dependent variables.Muscle aerobic capacity and strength of the quadriceps muscle independently contributed to endurance time on the treadmill (ET) in one model (overall R = 0.47, P < 0.01), and V̇O2max and strength of the quadriceps muscle independently contributed to ET in another model (R = 0.85, P < 0.001). In models of muscle strength, maximum creatine kinase activity and maximum anaerobic glycolytic rate independently contributed to triceps surae strength, after adjusting for triceps surae cross-section area (R = 0.63, P < 0.001). In another model, maximum creatine kinase activity was related to quadriceps strength independent of leg lean tissue (R = 0.31, P < 0.05). Rate of weight gain was related to muscle metabolic economy (r = −0.25, P = 0.04), quadriceps strength (r = −0.34, P < 0.01), V̇O2max (r = −0.22, P = 0.04), and ET (r = −0.21, P = 0.04). Rate of weight gain was modeled by muscle metabolic economy, V̇O2max, and quadriceps strength (R = 0.48, P < 0.01). Implications of findings are 1) greater strength and aerobic fitness—at the muscle and whole-body levels—improve endurance; 2) greater muscle anaerobic metabolism is associated with greater muscle strength, independent of muscle size; and 3) greater exercise endurance reduces weight gain.