Teske JA, Kotz CM. Effect of acute and chronic caloric restriction and metabolic glucoprivation on spontaneous physical activity in obesity-prone and obesity-resistant rats. Am J Physiol Regul Integr Comp Physiol 297: R176 -R184, 2009. First published May 6, 2009 doi:10.1152/ajpregu.90866.2008 and metabolic glucoprivation affect spontaneous physical activity (SPA), but it's unknown whether these treatments similarly affect SPA in selectively bred obesity-prone (OP) and -resistant (OR) rats. OR rats have greater basal SPA and are more responsive to treatments that modulate SPA, such as orexin A administration. We hypothesized that OR rats would be more sensitive to other treatments modulating SPA. To test this, continuous 24-h SPA was measured before and during acute (24 h) and chronic (8 wk) CR in OR, OP, and Sprague-Dawley rats. Pharmacological glucoprivation was produced by injection of 2-deoxyglucose (2-DG), and SPA was measured 5 h postinjection. Acute CR increased SPA in all groups; however, the effect was dependent on the index of SPA and time interval during the 24-h time period. In contrast to OR rats, chronic CR increased distance traveled, ambulatory episodes, and time spent in ambulation and stereotypy during the time interval preceding anticipation of food in OP and SpragueDawley rats. Although the effects of 2-DG treatment on SPA were minimal, OR rats had significantly greater SPA than OP and SpragueDawley rats independent of treatment. That chronic CR failed to result in significant changes in SPA in OR rats suggests that these rats may be especially unresponsive to treatments modulating feeding. This insensitivity coupled with elevated basal SPA levels may in part mediate phenotypic traits of lean rats. food deprivation; locomotor activity; diet-induced obesity THE RISING PREVALENCE OF OBESITY indicates that a sustained positive imbalance between energy intake and expenditure exists at the population level. However, it's unclear which factor, excessive intake or reduced energy expenditure, has contributed more to the obesity epidemic (19). Given the strong influence of genetics and environment on body weight gain, it's intriguing that spontaneous physical activity (SPA) has a strong familial and genetic component (65) and that lean adults and children display greater SPA than their obese counterparts (25,38). Similar to lean humans and nonhuman primates (63), rats selected for low weight gain [obesityresistant rats, (OR)] have greater SPA (57), body-weight adjusted SPA-associated energy expenditure (22), and nonresting energy expenditure (40). The response to treatments affecting food intake also differ between obese and lean rodents: weight gain following consumption of highly palatable diets (30) and weight regain after 50% caloric restriction (CR) is lower in OR rats (35). Further, fat oxidation was elevated in chow-fed OR rats (20). Moreover, total fat pad weight adjusted for body weight was significantly less in OR rats in response to early postweaning exercise (47). Hence, it's plausible t...