Effect of leptin deficiency on metabolic rate in ob/ob mice

Effect of leptin deficiency on metabolic rate in ob/ob mice
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DOI:
10.1152/ajpendo.1999.276.3.e443
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发表时间:
1999-03-01
影响因子:
5.1
通讯作者:
Berkowitz, DE
Berkowitz, DE
中科院分区:
医学2区
文献类型:
--
作者:
Breslow, MJ;Min-Lee, K;Berkowitz, DE

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代谢率降低可能导致瘦素缺乏(ob/ob)小鼠体重增加;然而,现有的研究因将O-2消耗量((V)除以点o(2))参考估计而不是真实的瘦体重而受到批评。为了评估瘦素缺乏是否会减少能量消耗,进行了四个独立的实验:1)NMR光谱用于测量脂肪和非脂肪质量,允许(V)在点o(2)上参考真正的非脂肪质量; 2)饮食控制用于试图消除ob/ob和C57 BL/6 J小鼠之间体重和成分的差异; 3)检测外源性瘦素(0.3 mg kg(-1)d(-1))对(V)的短期影响; 4)比较瘦素充足和成对喂养的ob ob动物的体重和组成。肥胖的动物有更大的质量,更少的瘦体重,和10%的代谢率高时,(V)超过点o(2)是指瘦体重。饮食操作在ob/ob和C57 BL/6 J动物中实现了相同的体重;然而,尽管C57 BL/6 J动物的体重增加,但ob/ob动物的脂肪量百分比仍然较高(55 vs 30%)。外源性瘦素在肥胖症/肥胖症动物中增加(V)超过0(2)点,但对照组动物没有。瘦素充足的ob ob小鼠的体重减轻大于配对喂养的动物(45 vs. 17%)。根据观察到的(V)比(2)点增加以及瘦素补充后体重减轻加快,我们得出结论,瘦素缺乏导致肥胖小鼠代谢率降低。相反,这些生理学研究表明,在肥胖和瘦的动物中比较(V)与点o(2)并没有产生关于瘦素对代谢的贡献的有用信息。
Reduced metabolic rate may contribute to weight gain in leptin-deficient (ob/ob) mice; however, available studies have been criticized for referencing O-2 consumption ((V) over dot o(2)) to estimated rather than true lean body mass. To evaluate whether leptin deficiency reduces energy expenditure, four separate experiments were performed: 1) NMR spectroscopy was used to measure fat and nonfat mass, permitting (V) over dot o(2) to be referenced to true nonfat mass; 2) dietary manipulation was used in an attempt to eliminate differences in body weight and composition between ob/ob and C57BL/6J mice; 3) short-term effects of exogenous leptin (0.3 mg kg(-1)day(-1)) on (V) over dot o(2) were examined; and 4)body weight and composition were compared in leptin-repleted and pair-fed ob lob animals. ob lob animals had greater mass, less lean body mass, and a 10% higher metabolic rate when (V) over dot o(2) was referenced to lean mass. Dietary manipulation achieved identical body weight in ob/ob and C57BL/6J animals; however, despite weight gain in C57BL/6J animals, percent fat mass remained higher in ob/ob animals (55 vs. 30%). Exogenous leptin increased (V) over dot o(2) in ob/ob but not control animals. Weight loss in leptin-repleted ob lob mice was greater than in pair-fed animals (45 vs. 17%). We conclude, on the basis of the observed increase in (V) over dot o(2) and accelerated weight loss seen with leptin repletion, that leptin deficiency causes a reduction in metabolic rate in ob lob mice. In contrast, these physiological studies suggest that comparison of (V) over dot o(2) in obese and lean animals does not produce useful information on the contribution of leptin to metabolism.