Effects Of LC Orexin-A On Spontaneous Activity In Obese Rats And Its Mechanism

Objective: To investigate the role of the locus coeruleus(LC) in enhanced orexin-A induced spontaneous activities of obesity-resistant rats and its mechanism and further explore whether LC associated with obesity resistance..Methods: Male Sprague-Dawley and selectively bred OR rats were used. A 26-gauge stainless steel cannula was directed towards the LC of rats. Orexin-A and the vehicle was injected through the cannula tract.And then, measured SPA, Indirect Calorimetry, total fat and fat-free mass. Adiposity was expressed by percent body fat. Results: Compared with SD rats,the OR rats had significantly lower body weight, fat and fat-free mass(P<0.05). OR rats showed significantly less adiposity(P<0.05) than SD rats. OR rats spent more time ambulating at 3 mo of age and spent more time vertical at 6 mo of age.This resulted in OR rats spending significantly more time moving as increase of age(P<0.05). After the injection of orexin-A, SPA of OR rats was higher than SD rats cause ambulating of OR rats significantly more than vertical activities. The OR rats have higher SPA, lower body weight, and yet the same daily energy expenditure as Sprague-Dawley rats which suggests that OR rats expend more energy on activities during the dark period. In OR rats, the two highest doses of orexin-A increased SPA significantly(P <0.05 for both doses) and this was dose dependent. In contrast, in Sprague-Dawley rats only the highest dose of orexin-A significantly increased SPA relative to vehicle(P <0.05).The two highest doses of orexin-A significantly increased SPA more robustly in OR rats relative to SD rats(250 pmol: P<0.05;500 pmol: P<0.05).Conclusions: Orexin-A infused into the LC stimulated SPA and related to obesity resistance.