Reduced voluntary activity precedes adult-onset obesity in Nhlh2 knockout mice
Reduced voluntary activity precedes adult-onset obesity in Nhlh2 knockout mice
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DOI：
10.1016/s0031-9384(02)00885-5
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发表时间：
2002-11-01
影响因子：
2.9
通讯作者：
Good, DJ
中科院分区：
文献类型：
--
作者：
Coyle, CA;Jing, EX;Good, DJ
神经元碱性螺旋-环-螺旋转录因子Nhlh 2的靶向缺失导致小鼠成年肥胖。在3-25周龄的动物中测量体重和身体组成表明，虽然雄性和雌性Nhlh 2敲除（N2 KO）动物均显示成年发病肥胖，但肥胖发展的时间框架不同，雌性在7周龄时变得肥胖，而雄性在10周龄时变得肥胖。杂合（HET）动物也变得肥胖，但具有较慢的发作，表明Nhlh 2转录因子活性的剂量效应。在肥胖前期和肥胖N2 KO、HET和野生型（WT）动物中测量食物摄入、体温和自主活动，以确定哪些因素导致体重增加。虽然在老年肥胖N2 KO动物中发现了食物摄入量增加和体温降低，但在N2 KO小鼠中，只有减少的体力活动才会出现肥胖。N2 KO动物在昼夜节律或平衡和运动控制方面没有缺陷，表明自愿活动减少是行为变化的结果。这些数据证明了Nhlh 2转录因子在控制对能量消耗重要的基因中的作用，并且更具体地，动物的自愿身体活动。(C)2002年由Elsevier Science Inc.出版
Targeted deletion of the neuronal basic helix-loop-helix transcription factor Nhlh2 results in adult-onset obesity in mice. Measurement of body weight and body composition in animals aged 3-25 weeks indicates that while male and female Nhlh2 knockout (N2KO) animals both show adult-onset obesity, the time frame for development of obesity is different, with females becoming obese by 7 weeks of age and males becoming obese by 10 weeks of age. Heterozygous (HET) animals also become obese but with a slower onset, indicating a dosage effect for the activity of the Nhlh2 transcription factor. Food intake, body temperature, and voluntary activity were measured in both preobese and obese N2KO, HET, and wild-type (WT) animals to determine which factors contributed to weight gain. While increased food intake and decreased body temperature were found in older obese N2KO animals, only reduced physical activity preceded the onset of obesity in N2KO mice. N2KO animals had no deficit in either circadian rhythm or balance and motor control, indicating that reduced voluntary activity is the result of a behavioral change. These data demonstrate a role for the Nhlh2 transcription factor in controlling genes important to energy expenditure, and more specifically voluntary physical activity of animals. (C) 2002 Published by Elsevier Science Inc.