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研究组成果介绍:瘦素对于野生啮齿动物适应寒冷环境具有重要作用
(王德华)
说明:试着介绍一下我们研究组的一些主要研究结果,与有兴趣的同行进行交流,希望能碰撞出点火花来。也希望欲加入我们研究组的学子们,能进一步了解我们的工作和进展。更欢迎对我们工作有兴趣的学子们,带着自己的创新想法和绝技加入到我们的研究队伍中来。
恒温动物对不同环境的适应机理一直是我们研究组关注和研究的主题。
温度对于动物的生存,尤其是恒温动物的生存,是影响最大的环境因素之一。在寒冷环境中,恒温动物由于维持稳定体温的需要,需要从生理和行为上进行一系列调整,以应对由于代谢产热增加而导致的自身能量需求的增加,这样能量平衡就显得非常重要。所谓的能量平衡,就是说动物摄取的能量与各种生理行为活动消耗的能量保持收支平衡。这样在动物适应寒冷环境的过程中,决定动物能量平衡的两个重要因素:能量摄入(摄食)和能量消耗(产热)都呈现出复杂而精细地调控。我们研究组选取栖息于内蒙古草原的野生布氏田鼠为研究对象,以近年发现在能量代谢调控中发挥关键作用的脂肪分泌的激素-瘦素(leptin)为切入点,对其在寒冷适应过程中的作用机制进行了研究。
布氏田鼠(Lasiopodomys brandtii)是一种严格的植食性啮齿动物,隶属于田鼠亚科毛足田鼠属,主要栖息在我国的内蒙古高原、邻近的蒙古和俄罗斯的贝加尔地区。动物的分布区冬季严寒而漫长,长达5个月,年温差和昼夜温差都很大,最低温可以达到
基于这种假设,我们将成年的布氏田鼠从温暖环境(
为了进一步验证我们上面的发现,我们对布氏田鼠体内施加外源瘦素。施加的方法是用一种微渗透泵,注入定量的瘦素后将其植入动物体内,渗透泵可以定量控制瘦素的分泌速率。经外源瘦素处理后,我们发现在冷驯化条件下的布氏田鼠摄食量明显减少,下丘脑AgRP和褐色脂肪组织BAT线粒体内膜上的解偶联蛋白1(uncoupling protein 1, UCP1)的表达也明显降低,统计表明AgRP和摄食量呈现显著的相关关系。在整个瘦素信号作用通路上的其它分子如瘦素的长型受体Ob-Rb、细胞信号抑制因子SOCS3、神经肽NPY、POMC和CART 等的表达则没有受到外源瘦素处理的影响。这些结果表明,与常温条件下的情况相比,在寒冷环境中瘦素水平对动物的摄食水平和产热能力的调控机制发生了改变。根据分析,我们认为增食类神经肽AgRP在这个调节过程中很可能扮演了重要角色。当然,这只是一个推测,尚需要进一步的实验验证。
这是我们最近的一个研究结果,已经发表在《美国生理学杂志》上(Tang GB, Cui JG and Wang DH 2009 American Journal Physiology - Regulatory Integrative and Comparative Physiology 297:1293-1301.)
名称术语:
褐色脂肪组织 (Brown adipose tissue , BAT);
解偶联蛋白1 (Uncoupling protein 1, UCP1);
非颤抖性产热 (Nonshivering thermogenesis, NST);
瘦素 (Leptin);
增食类神经肽:AgRP (agouti-related protein), NPY (neuropeptide Y);
厌食类神经肽: POMC (proopiomelanocortin)和CART (cocaine- and amphetamine-regulated peptide)
瘦素的长型受体(Ob-Rb);
细胞信号抑制因子SOCS3 (suppressor-of-cytokine-signaling 3)。
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Am J Physiol Regul Integr Comp Physiol. 2009 Nov;297(5):R1293-301. Epub 2009 Sep 2.
Role of hypoleptinemia during cold adaptation in Brandt's voles (Lasiopodomys brandtii).
State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Chaoyang, Beijing.
Brandt's voles Lasiopodomys brandtii exhibit large increases in nonshivering thermogenesis to cope with chronic cold exposure, resulting in compensatory hyperphagia and fat mobilization. These physiological events are accompanied by a remarkable reduction in serum leptin levels. However, the role of hypoleptinemia in cold adaptation in this species is still unknown. In the present study, we tested the hypothesis that hypoleptinemia contributes to increases in food intake and brown adipose tissue (BAT) thermogenesis by modifying hypothalamic neuropeptides in cold-exposed Brandt's voles. Adult male voles were transferred to 5 degrees C for 28 days. Accompanied by a decrease in serum leptin levels, hypothalamic agouti-related protein (AgRP) mRNA levels were significantly increased, but there were no changes in the long form of leptin receptor (Ob-Rb), suppressor of cytokine signaling 3 (SOCS3), neuropeptide Y (NPY) mRNA, proopiomelanocortin (POMC), and cocaine- and amphetamine-regulated peptide (CART) mRNA levels in the hypothalamus. When cold-exposed voles were returned to warm (23 degrees C) for 28 days, body mass, food intake, serum leptin, and AgRP mRNA were restored to control levels. Leptin administration in cold-exposed voles decreased food intake as well as hypothalamic AgRP mRNA levels. There were no significant effects of leptin administration on hypothalamic Ob-Rb, SOCS3, NPY, POMC, CART mRNA, and uncoupling protein 1 levels under cold conditions. These results suggest that hypoleptinemia partially contributes to cold-induced hyperphagia, which might involve the elevation of hypothalamic AgRP gene expression. PMID: 19726709 [PubMed - indexed for MEDLINE]
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