Dissertation Research: Hormonal Correlates of Prehibernatory Fattening in Bats Eric P. Widmaier and Kristy Townsend Boston 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.