Submitted on October 23, 2008
Revised on January 8, 2009
Accepted on January 8, 2009
Three-weeks of post-weaning exercise in DIO rats produces prolonged increases in central leptin sensitivity and signaling
Christa M. Patterson1, Sebastien G Bouret2, Ambrose A. Dunn-Meynell, and Barry E. Levin3*
1 New Jersey Medical School
2 the Saban Research Institute
3 VA Medical Center
* To whom correspondence should be addressed. E-mail: levin{at}umdnj.edu.
In rats selectively bred to develop diet-induced obesity (DIO), 3 wk of post-weaning exercise reduces weight and adipose regain for 10 wk after exercise cessation, despite intake of 31% fat high-energy (HE) diet. To test the hypothesis that this effect is due to increased central leptin sensitivity, 4 wk old DIO rats were fed HE diet and left sedentary (Sed), exercised for 3 wk and then remained sedentary for 10 additional weeks (Ex/Sed) or continued exercise for a full 13 wk (Ex). After 3 wk, leptin (5mg/kg,ip) induced a 36% decrease in 24 h food intake in Ex rats, while Sed rats had no change in 24 h intake. Ex rats also had 23% more leptin-induced phospho-STAT3 (pSTAT3)-expressing neurons in the arcuate nucleus (ARC) and 95% and 68% higher 125leptin receptor binding in the ventromedial and dorsomedial nuclei, than did Sed rats, respectively. At 7 wk after onset, leptin decreased 24 h intake by 20% in Ex and 24% in Ex/Sed rats without altering Sed intake. After a total of 13 wk, compared to Sed rats, Ex and Ex/Sed rats had 58% and 38% less fat, but leptin failed to decrease food intake in any group. Nevertheless, Ex, but not Ex/Sed rats still had 32% more ARC leptin-induced pSTAT3-expressing neurons than Sed rats. These data suggest that brief post-weaning exercise in DIO rats that are inherently leptin resistant causes a sustained resistance to obesity on HE diet which is, in part due to increased central leptin sensitivity.
