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.

The proteomic signature of insulin-resistant human skeletal muscle reveals increased glycolytic and decreased mitochondrial enzymes

“…Although the mitochondrial content and dysfunction in insulin-resistant states has been studied extensively [2-12, 32, 35, 36], few data exist about the potential role of glycolytic enzymes in insulin resistance. Consistent with increased glycolytic enzyme activity in insulin resistance are previous findings that the ratio between glycolytic (phosphofructokinase, GAPDH, hexokinase, PYGM) and oxidative enzyme activities (citrate synthase, cytochrome oxidase) was negatively correlated with insulin sensitivity [11], and that phosphofructokinase activity decreased upon 10% weight loss in obese individuals [37]. In contracting muscle, factors related to the energy state appear to control glycolysis [38], and therefore impaired mitochondrial function with less energy production could be responsible for increased glycolysis and, potentially, glycolytic enzyme abundance.…”

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

“…Although cachectic mice significantly reduced their locomotor activity in our study, total energy expenditure in cachectic mice remained elevated compared to pair-fed mice. While differences in muscle work efficiency may have contributed to the differences in total energy expenditure, 46,47 these data suggest that resting energy expenditure in cachectic mice is abnormally elevated in early cachexia when food intake is taken into consideration.…”

Extra Calories Cause Weight Gain—But How Much?

“…In addition, weight loss produces changes in hormones, the autonomic nervous system, and the intrinsic efficiency of muscle that serve to conserve energy. 3 Therefore, additional weight loss can only be achieved by a more severe diet or a more arduous physical activity routine. Most individuals do the opposite: after having achieved some weight loss, they resume their original diet and exercise habits.…”