目的:探讨Orexin-A对高脂饮食诱导的肥胖大鼠摄食和体重的影响。方法:通过检测SD大鼠24 h动态SPA的分布情况来定义HA大鼠和LA大鼠,创建饮食诱导肥胖(DIO)大鼠模型,向HA和LA大鼠延髓外侧下丘脑(rLH)和黑质多巴胺致密部(SN))微量注射orexin-A,观察orexin-A对能量消耗、自发动态运动(SPA)的作用,以及动态SPA对饮食诱导肥胖(DIO)的抵抗作用。结果:雄性SD大鼠在标准饮食情况下,24 h动态SPA呈正偏态分布,非固定SPA(ambulatory SPA)与瘦体重(lean mass,LM)(P〈0.05)以及总体重(P〈0.05)显著相关。HA和LA大鼠(high and low activity rats)间的固有SPA(intrinsic SPA)差异有显著统计学意义(P〈0.05)。与LA大鼠相比,HA大鼠延髓外侧下丘脑(rLH)和黑质多巴胺致密部(SN)的orexin-A反应性更高。在r LH和SN注射orexin-A能显著增加动态SPA(r LH:P〈0.05;SN:P〈0.05)。在HA和LA大鼠的r LH注射orexin-A,每种剂量与注射相同剂量的a CSF的大鼠相比效果有显著差异。而对于SN注射OXA,只有注射高剂量OXA的HA大鼠,与对照组相比,才出现著差异。在r LH注射OXA后,对HA/LA大鼠动态SPA均有显著影响(P〈0.05)。HA大鼠比LA大鼠能量消耗更高。不同的饮食对于HA和LA大鼠转化为SPA有不同的影响,HA大鼠对DIO敏感性低于LA大鼠。与LA大鼠相比,在LF(Low Fat)饮食条件下,转化为脂肪量的热量更少。结论:Orexin-A可通过增加大鼠活动量,使高脂饮食诱导的肥胖大鼠体重减轻。
Objective: To investigate the effect of orexin-A on food take and body weight in diet-induced obesity rats. Methods:After acclimation to the housing facilities, male Sprague-Dawley(SD) rats were classified rats as HA or LA on the basis of measurement of ambulatory and stereotypic SPAINT. Some of HA and LA rats were used to establish DIO models. Rats were prepared with unilateral cannulae targeting rLH or SN and orexin-A was injected as schedule. Body weight, fat and lean mass, food intake, SPA, indirect Calorimetry(IDC) of rats was measured. Results: There were significant differences in SPA between HA and LA rats but similar total body weight, fat mass. Higher level of ambulatory SPA was correlated with higher rLH orexin responsivity, and orexin regulation of SPA was distributed through multiple brain sites including the rLH and SN. Therefore, we proposed that HA rats might have higher rLH and SN orexin responsivity compared to LA rats. There were significant differences in rLH of HA and LA rats across all doses of orexin among individual doses of OXA against a CSF injection. On the contrary, for SN, there were only significant differences within HA rats at higher OXA. After adjustment for total body mass, HA rats showed significantly higher EE than LA rats(P0.05) while there were no differences in uncorrected EE between HA and LA rats averaged over IDC recording sessions doses. LA rats had higher DIO sensitivity than HA rats. Conclusions: Orexin A signaling contributes to the observed variations in SPA and DIO sensitivity.