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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Academic Research Enhancement Awards (AREA) (R15)
Project #
Application #
Study Section
Molecular and Cellular Endocrinology Study Section (MCE)
Program Officer
Hyde, James F
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Miami University Oxford
Schools of Arts and Sciences
United States
Zip Code
Cao, Jingyi; Zhu, Qi; Liu, Lin et al. (2018) Global Transcriptome Analysis of Brown Adipose Tissue of Diet-Induced Obese Mice. Int J Mol Sci 19:
Kalyani, Manu; Callahan, Phyllis; Janik, James M et al. (2017) Effects of Pup Separation on Stress Response in Postpartum Female Rats. Int J Mol Sci 18:
Kalyani, Manu; Hasselfeld, Kathryn; Janik, James M et al. (2016) Effects of High-Fat Diet on Stress Response in Male and Female Wildtype and Prolactin Knockout Mice. PLoS One 11:e0166416
Shen, Minqian; Shi, Haifei (2016) Estradiol and Estrogen Receptor Agonists Oppose Oncogenic Actions of Leptin in HepG2 Cells. PLoS One 11:e0151455
Shi, Haifei; Brown, Lynda M; Rahimian, Roshanak (2015) Sex/Gender Differences in Metabolism and Behavior: Influence of Sex Chromosomes and Hormones. Int J Endocrinol 2015:245949
Liu, Xian; Shi, Haifei (2015) Regulation of Estrogen Receptor ? Expression in the Hypothalamus by Sex Steroids: Implication in the Regulation of Energy Homeostasis. Int J Endocrinol 2015:949085
Shen, Minqian; Shi, Haifei (2015) Sex Hormones and Their Receptors Regulate Liver Energy Homeostasis. Int J Endocrinol 2015:294278
Gavini, Chaitanya K; Mukherjee, Sromona; Shukla, Charu et al. (2014) Leanness and heightened nonresting energy expenditure: role of skeletal muscle activity thermogenesis. Am J Physiol Endocrinol Metab 306:E635-47
Shen, Minqian; Kumar, Shiva P D Senthil; Shi, Haifei (2014) Estradiol regulates insulin signaling and inflammation in adipose tissue. Horm Mol Biol Clin Investig 17:99-107
Zhu, Zheng; Spicer, Elizabeth G; Gavini, Chaitanya K et al. (2014) Enhanced sympathetic activity in mice with brown adipose tissue transplantation (transBATation). Physiol Behav 125:21-9

Showing the most recent 10 out of 16 publications