Regular exercise attenuates the metabolic drive to regain weight after long-term weight loss

1 Center for Human Nutrition, Department of Medicine, 2 Division of Endocrinology, Diabetes, and Metabolism, and 3 Department of Pediatrics, University of Colorado Denver, Denver, Colorado Submitted 2 April 2009 ; accepted in final form 1 July 2009 Weight loss is accompanied by several metabolic adaptations that work together to promote rapid, efficient regain. We employed a rodent model of regain to examine the effects of a regular bout of treadmill exercise on these adaptations. Obesity was induced in obesity-prone rats with 16 wk of high-fat feeding and limited physical activity. Obese rats were then weight reduced ( 14% of body wt) with a calorie-restricted, low-fat diet and maintained at that reduced weight for 8 wk by providing limited provisions of the diet with (EX) or without (SED) a daily bout of treadmill exercise (15 m/min, 30 min/day, 6 days/wk). Weight regain, energy balance, fuel utilization, adipocyte cellularity, and humoral signals of adiposity were monitored during eight subsequent weeks of ad libitum feeding while the rats maintained their respective regimens of physical activity. Regular exercise decreased the rate of regain early in relapse and lowered the defended body weight. During weight maintenance, regular exercise reduced the biological drive to eat so that it came closer to matching the suppressed level of energy expenditure. The diurnal extremes in fuel preference observed in weight-reduced rats were blunted, since exercise promoted the oxidation of fat during periods of feeding (dark cycle) and promoted the oxidation of carbohydrate (CHO) later in the day during periods of deprivation (light cycle) . At the end of relapse, exercise reestablished the homeostatic steady state between intake and expenditure to defend a lower body weight. Compared with SED rats, relapsed EX rats exhibited a reduced turnover of energy, a lower 24-h oxidation of CHO, fewer adipocytes in abdominal fat pads, and peripheral signals that overestimated their adiposity. These observations indicate that regimented exercise altered several metabolic adaptations to weight reduction in a manner that would coordinately attenuate the propensity to regain lost weight. fat oxidation; energy balance; indirect calorimetry; postobese; adipocyte cellularity Address for reprint requests and other correspondence: P. S. MacLean, Univ. of Colorado Denver, Center for Human Nutrition, Mailstop F8305, PO Box 6511, 12800 East 19th Ave., Aurora, CO 80045 (e-mail: paul.macle