Effects of adiponectin on metabolic syndrome : analysis of transgenic mice expressing high levels of adiponectin

为了评估慢性高脂联素血症对代谢表型的影响，我们建立了3系在B6背景下表达人全长脂联素的转基因小鼠。在高脂肪/高蔗糖饮食中，表达高水平脂联素的转基因小鼠表现出显著降低的体重增加，与野生型B6小鼠相比，内脏和皮下脂肪组织中的脂肪积累较少，脂肪细胞较小。转基因小鼠的直肠温度较高，每日耗氧量较大，呼吸商较低。此外，高热量饮食诱导的氧化性DNA损伤显着减弱，在高脂联素血症的小鼠，尽管没有改变的食物消耗。通过重复回交将人脂联素转基因转移到KK-A-γ小鼠中。表达人脂联素的KK-A-γ小鼠在常规食物中也显示出提高的耗氧率、减少的体重增加和改善的胰岛素对外源性胰岛素的敏感性，证实了脂联素对肥胖相关代谢紊乱的有益作用。

To assess the effects of chronic hyperadiponectinemia on metabolic phenotypes, we established 3 lines of Transgenic mice expressing human full length adiponectin on B6 background. On high fat/high sucrose diet, the transgenic mice expressing high levels of adiponectin exhibited significantly decreased weight gain associated with less fat accumulation and smaller adipocytes in both the visceral and subcutaneous adipose tissues than wild-type B6 mice. The transgenic mice had higher rectal temperature, and greater daily oxygen consumption with a lower respiratory quotient. Moreover, high-calorie diet-induced oxidative DNA damage was significantly attenuated in the hyperadiponectinemic mice, despite unaltered food consumption. The human adiponectin transgene was transferred to KK-A^y mice by repeated back crosses. KK-A^y mice expressing human adiponectin also showed on regular chow elevated oxygen consumption rate, reduced weight gain, and improved insulin sensitivity to exogenous insulin, confirming the beneficial effects of adiponectin on obesity-related metabolic disorders.