Effects of experimental weight perturbation on skeletal muscle work efficiency, fuel utilization, and biochemistry in human subjects

Abstract

Maintenance of a body weight 10% above or below that "customary" for lean or obese individuals results in respective increases or decreases in the energy expended in low levels of physical activity (nonresting energy expenditure, NREE). These changes are greater than can be accounted for by the altered body weight or composition and are due mainly to altered skeletal muscle work efficiency at low levels of power generation. We performed biochemical analysis of vastus lateralis muscle needle biopsy samples to determine whether maintenance of an altered body weight was associated with changes in skeletal muscle histomorphology. We found that the maintenance of a 10% reduced body weight was associated with significant declines in glycolytic (phosphofructokinase, PFK) enzyme activity and, in particular, in the ratio of glycolytic to oxidative (cytochrome c oxidase, COX) enzyme activity without significant changes in the activities of enzymes relevant to mitochondrial density, respiratory chain activity, or fuel transport; or in skeletal muscle fiber type or glycogen stores. The fractional change in the ratio of PFK/COX activity in subjects following weight loss was significantly correlated with changes in the systemic respiratory exchange ratio (RER) and measures of mechanical efficiency of skeletal muscle at low workloads (pedaling a bicycle to generate 10 or 25 W of power). Thus, predictable changes in systemic skeletal muscle biochemistry accompany the maintenance of an altered body weight and account for a significant portion of the variance in skeletal muscle work efficiency and fuel utilization at reduced body weight.

Fig. 1.

Means ± SE percent change in bicycle ergometry, MRS, and in vitro skeletal muscle biopsy data from Wt_initial. Maintenance of a reduced body weight (Wt_−10%) is associated with a significant reduction in the respiratory exchange ratio (RER) during low-level exercise (bicycling to generate 10–25W of power) and muscle phosphofructokinase (PFK) and ratio of PFK/cytochrome c oxidase (COX). Maintenance of an elevated body weight (Wt_+10%) is associated with a significant increase in RER during low-level exercise (bicycling to generate 10 W of power). HADH, 2-hydroxyacyl CoA dehydrogenase activity. *P < 0.05 compared with zero.

Fig. 2.

Correlations of the ratios of glycolytic (PFK) to fatty acid oxidative (COX) enzyme activities with skeletal muscle work efficiency (solid circles) and the respiratory exchange ratio (RER, solid squares) during low-level exercise (bicycling to generate 10 W of power) at usual body weight (Wt_initial). Regression equations are efficiency = −0.0026(PFK/COX) + 0.11, R² = 0.26, P < 0.01. RER = −0.00098 (PFK/COX) + 0.82, R² = 0.025, not significant.

Fig. 3.

Correlations of the percentage changes in ratios of glycolytic (PFK) to fatty acid oxidative (COX) enzyme activities with skeletal muscle work efficiency (solid circles) and the RER (solid squares) during low-level exercise (bicycling to generate 10 W of power) in subjects studied before (Wt_initial) and after (Wt_−10%) weight loss. Regression equations are percentage change in efficiency = −1.38 (PFK/COX) + 1.54, R² = 0.56, P < 0.0001 and percentage change in RER = 0.48 (PFK/COX) − 3.81, R² = 0.29; P = 0.008