Identification of a physiological role for leptin in the regulation of ambulatory activity and wheel running in mice
Identification of a physiological role for leptin in the regulation of ambulatory activity and wheel running in mice
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DOI：
10.1152/ajpendo.00546.2010
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发表时间：
2011-02-01
影响因子：
5.1
通讯作者：
Wisse, Brent E.
中科院分区：
文献类型：
--
作者：
Morton, Gregory J.;Kaiyala, Karl J.;Wisse, Brent E.
莫顿GJ，Kaiyala KJ，Fisher JD，Ogimoto K，Schwartz MW，Wisse Be。确定瘦素在调节小鼠行走活动和车轮运行中的生理作用。AM J生理学内分泌代谢酶300：E392-E401,2011。2010年11月9日首次出版；DOI：10.1152/ajpendo.00546.2010-尽管有证据表明有影响的遗传和后天因素，但调节自发体力活动的机制仍然缺乏特征。我们评估了瘦素缺乏的ob/ob小鼠和皮下注射瘦素前后禁食表现为低血浆症的野生型小鼠的步行活动和车轮运行情况。在ob/ob小鼠中，对野生型小鼠特有的血浆瘦素水平的治疗以剂量依赖的方式显著增加了行走活动(每暗周期增加4,000+/-200束中断，P<；0.05)和总能量消耗(TEE；在暗周期增加0.11+/-0.01千卡/小时，P<；0.05)，并显著增加了轮子跑(+350%，P<；0.05)。禁食有效地增加了野生型小鼠的行走活动和车轮跑动(AA：+25%，P<；0.05；车轮跑步：+80%，P<；0.05)，并且禁食对ob/ob小鼠的影响更为明显(AA：+400%，P<；0.05；车轮跑步：+1600%，P<；0.05)。然而，与随意喂养的ob/ob小鼠不同的是，生理性的瘦素替代减弱或阻止了禁食诱导的行走活动和轮子运行的增加，在野生型和ob/ob小鼠中都是如此。因此，血浆瘦素是自发身体活动的生理调节器，但瘦素对活动的影响的性质取决于食物的可获得性。
Morton GJ, Kaiyala KJ, Fisher JD, Ogimoto K, Schwartz MW, Wisse BE. Identification of a physiological role for leptin in the regulation of ambulatory activity and wheel running in mice. Am J Physiol Endocrinol Metab 300: E392-E401, 2011. First published November 9, 2010; doi: 10.1152/ajpendo.00546.2010.-Mechanisms regulating spontaneous physical activity remain poorly characterized despite evidence of influential genetic and acquired factors. We evaluated ambulatory activity and wheel running in leptin-deficient ob/ob mice and in wild-type mice rendered hypoleptinemic by fasting in both the presence and absence of subcutaneous leptin administration. In ob/ob mice, leptin treatment to plasma levels characteristic of wild-type mice acutely increased both ambulatory activity (by 4,000 +/- 200 beam breaks/dark cycle, P < 0.05) and total energy expenditure (TEE; by 0.11 +/- 0.01 kcal/h during the dark cycle, P < 0.05) in a dose-dependent manner and acutely increased wheel running (+350%, P < 0.05). Fasting potently increased ambulatory activity and wheel running in wild-type mice (AA: +25%, P < 0.05; wheel running: +80%, P < 0.05), and the effect of fasting was more pronounced in ob/ob mice (AA: +400%, P < 0.05; wheel running: +1,600%, P < 0.05). However, unlike what occurred in ad libitum-fed ob/ob mice, physiological leptin replacement attenuated or prevented fasting-induced increases of ambulatory activity and wheel running in both wild-type and ob/ob mice. Thus, plasma leptin is a physiological regulator of spontaneous physical activity, but the nature of leptin's effect on activity is dependent on food availability.