Induction of uncoupling protein expression in brown and white adipose tissue by leptin
Induction of uncoupling protein expression in brown and white adipose tissue by leptin
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DOI：
10.1210/en.140.1.292
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发表时间：
1999-01-01
期刊：
影响因子：
4.8
通讯作者：
Gettys, TW
中科院分区：
文献类型：
--
作者：
Commins, SP;Watson, PM;Gettys, TW
当能量摄入长期超过能量消耗时，发生过量体脂的沉积。在ob/ob小鼠中，瘦素的缺乏影响能量平衡方程的两个分量，并且小鼠在断奶后变得病态肥胖。用外源性瘦素治疗ob/ob小鼠通过减少食物摄入和刺激能量利用来降低体重，但是即使当盐水和瘦素注射的ob/ob小鼠成对喂养时，接受瘦素的小鼠也显著减轻体重。因此，本研究的目的是测试的假设，解偶联蛋白-1（UCP 1）的表达减少，从ob/ob小鼠的脂肪组织，并恢复与外源性瘦素治疗。将瘦小鼠和ob/ob小鼠（5-6周龄）在23 ℃下饲养并用瘦素（20 μ g/g BW.day）处理3天，然后将它们杀死。与同窝瘦鼠相比，ob/ob小鼠棕色脂肪组织（BAT）和腹膜后白色脂肪组织（WAT）中UCP 1信使RNA（mRNA）和蛋白水平较低。用瘦素治疗ob/ob小鼠体重减轻，并且在肩胛间BAT和腹膜后WAT中产生4- 5倍的UCP 1 mRNA水平增加。UCP 1 mRNA的增加伴随着来自每个组织的线粒体制备物中UCP 1蛋白的可比增加。鉴于UCP 1的唯一已知功能是解偶联氧化磷酸化，本研究结果与瘦素通过增加产热活性和能力（UCP 1）刺激ob/ob小鼠能量利用的结论一致。此外，本研究结果表明，UCP 1在ob/ob小鼠的BAT和WAT中的表达降低是导致其代谢效率增加和肥胖倾向的部分原因。
Deposition of excess body fat occurs when energy intake chronically exceeds energy expenditure, In ob/ob mice, the absence of leptin affects both components of the energy balance equation, and the mice become morbidly obese after weaning. Treatment of ob/ob mice with exogenous leptin reduces body weight by decreasing food intake and stimulating energy utilization, but even when saline- and leptin-injected ob/ob mice are pair-fed, mice receiving leptin lose significantly more weight. Therefore, the purpose of the present study was to test the hypotheses that uncoupling protein-1 (UCP1) expression is reduced in adipose tissue from ob/ob mice and is restored by treatment with exogenous leptin. Lean and ob/ob mice (5-6 weeks old) were housed at 23 C and treated with leptin (20 mu g/g BW.day) for 3 days before they were killed. Compared with levels in lean littermates, UCP1 messenger RNA (mRNA) and protein levels were lower in brown adipose tissue (BAT) and retroperitoneal white adipose tissue (WAT) from ob/ob mice. Treatment of ob/ob mice with leptin reduced body weight and produced a 4- to 5-fold increase in UCP1 mRNA levels in both interscapular BAT and retroperitoneal WAT. The increases in UCP1 mRNA were accompanied by comparable increases in UCP1 protein in mitochondrial preparations from each tissue. Given that the sole known function of UCP1 is to uncouple oxidative phosphorylation, the present results are consistent with the conclusion that leptin stimulates energy utilization in ob/ob mice by increasing thermogenic activity and capacity (UCP1). In addition, the present results suggest that decreased UCP1 expression in BAT and WAT of ob/ob mice is in part responsible for their increased metabolic efficiency and propensity to become obese.