Obesity is a major health problem worldwide. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays essential roles in the regulation of energy balance in many species including humans. Thus, BDNF system could be one of the therapeutic targets for prevention and treatment of obesity. There is increasing evidence that regulation of energy balance and metabolism is not the same for both genders. Previous studies suggest that BDNF activates sympathetic nervous system to regulate metabolism. However, the exact neural circuit responsible for BDNF-induced energy metabolism is unknown. Additionally, females are more sensitive to BDNF's effects on the regulation of energy balance than males. The underlying neural mechanism for the sex differences in energy metabolism regulated by BDNF is unknown. This project will examine potential neural mechanism of BDNF system in regulating energy metabolism in male and female rats. First, the central nervous system-peripheral tissue circuit involving BDNF will be identified. Then changes in specific sympathetic molecular markers and sympathetic drive to metabolic tissues by BDNF administration will be assessed. Collectively, this project will provide direct neuroanatomical, neurofunctional, molecular, and neurochemical evidence underlying the mechanisms of BDNF's effects on metabolism and energy homeostasis. Additionally, this project will provide important new information about sex differences in response to BDNF administration. Such information is invaluable for identifying gender-specific biological targets for intervention to prevent or treat obesity. Furthermore, this project provides plentiful opportunities for graduate and undergraduate students to participate in research and to enhance research environment at Miami University, in agreement with the R15 mission.
As the prevalence of overweight and obesity is rising, the incidence of type 2 diabetes, cardiovascular disease, and some types of cancer is increasing at a similar alarming rate. It is essential that novel therapeutic and prevention strategies for obesiy are developed and this can only be achieved by attaining a clear understanding of the factors contributing to energy balance. The central nervous system receives information from the periphery relevant to an individual's energy balance through metabolic, neural, and endocrine signals. Understanding the neuroendocrine (brain-hormone) control of body weight regulation is critical before specific treatments can be identified. Brain-derived neurotrophic factor (BDNF) is an essential neuropeptide that plays an integral role in energy balance and metabolism in the CNS via activating sympathetic nervous system. There is increasing evidence that the regulation of body weight is not the same for both genders. The underlying neuroendocrine mechanisms of sex differences in energy homeostasis have not been unequivocally discerned. The results obtained from the studies proposed in this R15 proposal will elucidate and identify sex differences in the regulation of the BDNF signaling system with the long term goal to generate data that will be useful in developing gender-specific therapeutics to treat or prevent obesity.
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