The ventromedial hypothalamus (VMH) is known to be involved in the regulation of energy metabolism but it may also modulate locomotor activity. Since prolonged fasting is marked by a succession of changes in energy utilization and locomotor activity, it was hypothesized that VMH may be a critical link controlling mobilization of energy stores and/or behavioral changes in response to fasting. To test this, the changes in rate of body mass loss, body content in lipid and protein, acid wheel-running activity were studied in fasted nonobese rats with VMH electrolytic lesions. Secondary effects of VMH obesity were ruled out by postoperative restricted feeding. During fasting, VMH lesions impaired neither the overall lipid mobilization nor the late rise in daily body mass loss, concomitant with the increase in net proteolysis. Despite that the onset of this late stage of fasting was significantly delayed in VMH vs. sham-operated rats (13 +/- 1 vs. 8 +/- 1 days, respectively), the final amount of reserve lipids (3 g) was closely similar in both groups: this is the first experimental evidence of the hypothesis of a lipidic set-point. These results indicate that VMH is not a critical link controlling the time-course of utilization of energy reserves. The increase in diurnal (and total) daily wheel-running observed in fasted sham-operated rats still occurred in fasted VMH rats but was significantly reduced and delayed. VMH nuclei and/or associated fibers are therefore involved in the fasting-induced rise in diurnal activity.
