Dissertation Research: Changes in Leptin Biology During Prehibernation in Bats

论文研究：蝙蝠冬眠前增肥的激素相关性肥胖与人类和其他动物的不良健康后果有关。 然而，增加的脂肪积累也是许多动物生命史某些阶段的重要生存适应。 例如，脂肪沉积有利于成功怀孕。 另一个适应性增肥的例子发生在冬眠的哺乳动物身上。 然而，季节性动物如何存款足够的脂肪储存以度过冬眠目前还没有解决;阐明冬眠前增肥的机制是这项研究的一个关键的长期目标。瘦素是哺乳动物脂肪组织与大脑沟通的重要激素。 瘦素是由脂肪细胞产生的，与身体脂肪成比例。 它通过激活细胞信号分子在大脑中起作用，导致代谢率增加和食欲下降。 在冬眠前的这段时间里，脂肪必须积累起来，大脑必须以某种方式忽略瘦素抑制食欲的作用。 这种情况可能发生的一种方式是，如果大脑细胞通常对瘦素做出反应，由于信号分子或瘦素受体减少而失败。 第二种方法是减少脂肪组织分泌的瘦素。 本计画将借由在小棕蝠冬眠前或冬眠期间的体外脂肪组织分泌瘦素来测试这两种可能性。 瘦素基因的激活状态将使用称为MALDI-TOF-质谱的复杂程序来确定，该程序能够区分DNA中修饰碱基与未修饰碱基的比例（基因激活的一种关键方式的标记）。 此外，将检查动物的大脑，以检验瘦素受体的活性形式和受体产生的信号分子在冬眠前减少的假设。 选择小棕蝠作为实验对象动物有很多原因。 它们非常丰富，存在于非常大的，繁荣的产妇群体和冬眠前群体中，在生态学上具有重要意义，并且在基本生理学和繁殖方面是最好理解的冬眠动物之一，为这项研究提供了大量的信息。更广泛的影响，这项研究包括：一个研究生和几个本科生在野外生物学和分子内分泌学的综合培训;提供关键信息的生存策略，在生态上重要的哺乳动物的顺序;和可能的关系瘦素生物学的季节性变化的机制异常瘦素生物学肥胖。

Dissertation Research: Hormonal Correlates of Prehibernatory Fattening in BatsEric P. Widmaier and Kristy TownsendBoston University Obesity is associated with adverse health consequences in people and other animals. However, increased fat accumulation is also an important survival adaptation during certain stages of the life histories of many animals. For example, fat deposition is beneficial to successful pregnancies. Another example of adaptive fattening occurs in hibernating mammals. How seasonal animals deposit adequate fat stores to survive hibernation is currently unresolved, however; clarifying the mechanism of prehibernatory fattening is a key long-term goal of this research. Leptin is an important hormone through which adipose tissue communicates with the brain in mammals. Leptin is produced by adipose cells in proportion to body fat. It acts within the brain by activating cell signaling molecules that result in increased metabolic rate and decreased appetite. During the prehibernatory period, when fat must be accumulated, the brain must somehow ignore the appetite-suppressing action of leptin. One way in which this could happen is if the cells of the brain which normally respond to leptin, fail to do because of reduced signaling molecules or leptin receptors. A second way in which the brain can be released from leptin inhibition is to reduce the amount of leptin secreted by adipose tissue. This project will test both possibilities by examining adipose tissue secretion of leptin in vitro in little brown bats before or during the prehibernatory fattening period. The activational state of the leptin gene will be determined using a sophisticated procedure called MALDI-TOF-mass spectrometry, which is capable of distinguishing the ratio of modified bases in DNA to non-modified bases (a marker of one key way in which genes are activated). In addition, the brains of the animals will be examined to test the hypothesis that active forms of the leptin receptor and the signaling molecules generated by the receptors are decreased in the prehibernatory period. Little brown bats are chosen as experimental subject animal for many reasons. They are extremely abundant and exist in very large, thriving maternity colonies and prehibernatory colonies, are of great importance ecologically, and are among the most well-understood hibernators in terms of their basic physiology and reproduction, providing substantial information on which to base this study. Broader impacts of this research include: integrated training of one graduate student and several undergraduate students in field biology and molecular endocrinology; providing critical information about survival strategies in an ecologically important mammalian order; and possible relation of mechanisms of seasonal changes in leptin biology to abnormal leptin biology in obesity.