Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota, USA.
Obesity (Silver Spring). 2013 Feb;21(2):353-60. doi: 10.1002/oby.20045.
Humans and rodents show large variability in their individual sensitivity to diet-induced obesity (DIO), which has been associated with differences in intrinsic spontaneous physical activity (SPA). Evidence from genetic and out-bred rat obesity models shows that higher activity of the orexin peptides results in higher intrinsic SPA and protection against DIO. Based on this, we hypothesized that naturally occurring variation in SPA and orexin signaling is sufficient to drive differences in sensitivity to DIO.
Orexin expression, behavioral responses to orexin-A, basal energy expenditure and sensitivity to DIO were measured in in non-manipulated male Sprague-Dawley rats selected for high and low intrinsic SPA.
Male Sprague-Dawley rats were classified as high-activity or low-activity based on differences in intrinsic SPA. High-activity rats showed higher expression of prepro-orexin mRNA, higher sensitivity to behavioral effects of orexin injection, higher basal energy expenditure and were more resistant to obesity caused by high-fat diet consumption than low-activity rats.
Our results define a new model of differential DIO sensitivity, the high-activity and low-activity rats, and suggest that naturally occurring variations in intrinsic SPA cause differences in energy expenditure that are mediated by orexin signaling and alter DIO sensitivity.
人类和啮齿动物在个体对饮食诱导肥胖（DIO）的敏感性方面存在很大差异，这与内在自发性体力活动（SPA）的差异有关。来自遗传和杂交肥胖大鼠模型的证据表明，食欲肽的活性更高会导致更高的内在 SPA，并能预防 DIO。基于这一点，我们假设 SPA 和食欲肽信号的自然变异足以导致对 DIO 敏感性的差异。
在选择具有高和低内在 SPA 的雄性 Sprague-Dawley 大鼠中测量了食欲肽的表达、对食欲肽-A 的行为反应、基础能量消耗和对 DIO 的敏感性。
雄性 Sprague-Dawley 大鼠根据内在 SPA 的差异分为高活性或低活性。高活性大鼠表现出更高的前食欲肽 mRNA 表达，对食欲肽注射的行为效应更敏感，基础能量消耗更高，并且比低活性大鼠更能抵抗高脂肪饮食引起的肥胖。
我们的研究结果定义了一种新的 DIO 敏感性差异模型，即高活性和低活性大鼠，并表明内在 SPA 的自然变异会导致能量消耗的差异，这些差异是由食欲肽信号介导的，并改变了 DIO 的敏感性。
