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

脂联素对代谢综合征的影响：表达高水平脂联素的转基因小鼠的分析

• 批准号: 16590897
• 负责人: YAMADA Kentaro
• 金额: $ 2.3万
• 依托单位: KURUME UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590897/
• 关键词: adiponectin; transgenic mouse; metabolic syndrome; obesity; hyperlipidemia; KK-A^y mouse; トランスジェニックマウス; 代謝症候群

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.

为了评价慢性高脂联素血症对代谢表型的影响，我们建立了3株以B6为背景表达人全长脂联素的转基因小鼠。在高脂肪/高蔗糖饮食中，与野生型B6小鼠相比，高表达脂联素的转基因小鼠体重增加显著减少，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更高，日耗氧量更大，呼吸商更低。此外，高卡路里饮食诱导的氧化DNA损伤在高脂联素血症小鼠中显著减轻，尽管食物摄入量没有改变。用重复回交的方法将人脂联素基因导入KK-A^y小鼠体内。表达人脂联素的KK-A^y小鼠在正常饮食条件下也表现出氧耗率增加、体重增加减少、胰岛素对外源胰岛素的敏感性提高等表现，证实了脂联素对肥胖相关代谢紊乱的有益作用。