Suppressed sympathetic outflow to skeletal muscle, muscle thermogenesis, and activity energy expenditure with calorie restriction

During weight loss, adaptive thermogenesis occurs where energy expenditure (EE) is suppressed beyond that predicted for the smaller body size. Here, we investigated the contributions of resting and nonresting EE to the reduced total EE seen after 3 weeks of 50% calorie restriction (CR) in rats, focusing on activity‐associated EE, muscle thermogenesis, and sympathetic outflow. Prolonged food restriction resulted in a 42% reduction in daily EE, through a 40% decrease in resting EE, and a 48% decline in nonresting EE. These decreases in EE were significant even when the reductions in body weight and lean mass were taken into account. Along with a decreased caloric need for low‐to‐moderate‐intensity treadmill activity with 50% CR, baseline and activity‐related muscle thermogenesis were also suppressed, though the ability to increase muscle thermogenesis above baseline levels was not compromised. When sympathetic drive was measured by assessing norepinephrine turnover (NETO), 50% CR was found to decrease NETO in three of the four muscle groups examined, whereas elevated NETO was found in white adipose tissue of food‐restricted rats. Central activation of melanocortin 4 receptors in the ventromedial hypothalamus stimulated this pathway, enhancing activity EE; this was not compromised by 50% CR. These data suggest that suppressed activity EE contributes to adaptive thermogenesis during energy restriction. This may stem from decreased sympathetic drive to skeletal muscle, increasing locomotor efficiency and reducing skeletal muscle thermogenesis. The capacity to increase activity EE in response to central stimuli is retained, however, presenting a potential target for preventing weight regain.