Adaptation to low calorie intake in obese mice: contribution of a metabolic component to diminished energy expenditures during and after weight loss

Abstract

Adaptive changes in energy expenditure (EE) in response to low calorie intake were assessed quantitatively in obese mice using techniques that measure EE chronically over weeks (by the comparative carcass method), and also over 24 h (by indirect calorimetry). Grossly obese mice were slimmed (by restricting food to 50 per cent of normal intake) until their body weight reached that of the lean. They were subsequently either maintained in the post-obese state by continued food restriction at 25 per cent below the obese controls, or refed at the same calorie intake as controls. Total EE (assessed over 3 week periods) fell by 30 per cent during weight loss (obese controls 1356 kJ vs obese-slimmed 966 kJ, P less than 0.001), by 25 per cent during maintenance of the post-obese weight (obese control 1443 kJ vs post-obese 1062 kJ, P less than 0.001), and remained diminished by 17 per cent during weight regain upon refeeding (obese control 1443 kJ vs slimmed/refed 1176 kJ, P less than 0.001). Similar reductions in daily oxygen consumption were also obtained by indirect calorimetry, and as a function of lean body mass, 24 h VO2 were lower than controls by 17 per cent, 9 per cent and 10 per cent respectively (P less than 0.01 at least), and remained so under conditions of locomotory restraint. It is calculated that in these obese mice, a metabolic component (unassociated with changes in lean body mass and activity) comprised nearly two-thirds of the adaptive fall in EE during weight loss, and one-half of the change in EE during both phases of post-obese weight maintenance and during weight regain. These studies therefore support the notion that in response to low calorie intake, adaptive changes in the efficiency of cellular energy utilization are of considerable quantitative importance in the resistance to weight loss and in the ease with which the obese condition is rapidly regained after slimming.