Our scientific interest is to unravel the mechanism by which the central nervous system (CNS) regulates whole body metabolic homeostasis such as glucose and fat metabolism, energy expenditure, and food intake. Obesity and metabolic diseases have been increasing at the alarming rate and threatening our health and economy over the world. Understanding the mechanism underlying the regulation of metabolism is a fundamental step towards to designing new treatments for obesity and its associated diseases, and many other metabolic diseases. To unravel the mechanism by which the CNS regulates metabolism, we will utilize a variety of technique including, but not limited, generating transgenic animals, optogenetics, chemogenetics, in situ hybridization, immunohistochemistry, and biochemical assay. Currently, our lab is focused on two projects
1) The CNS regulates metabolic adaptations to high physical activity
Most, if not all, animals have evolved in the environment in which high physical activity is required in order to seek food for surviving. Our genetics is optimized to this metabolically challenging environment, and not ready for our modern sedentary lifestyle. Human and rodents studies have shown that high physical activity or exercise training can dramatically improve metabolism. A part of beneficial effects of exercise on metabolism results from metabolic adaptations to exercise such as increases the metabolic capacity of the skeletal muscle. Our lab will investigate the contributions of the CNS to metabolic adaptations to exercise.
2) The CNS regulates glucose metabolism independently of insulin
Insulin, which is secreted from pancreatic beta-cells, is essential for life. In fact, a person who lacks insulin develops severe disease, type 1 diabetes mellitus (T1DM). Insulin treatment has been saving the life of T1DM patients, yet the treatment is not still perfect. For instance, T1DM patients have a higher risk of cardiovascular diseases compared to same age of non-T1DM subjects. Previously we found that the CNS has a capability to regulate glucose metabolism independently of insulin. Our aim is to unravel the precise neuronal and molecular mechanism by which the CNS regulates glucose metabolism without insulin.
Fujikawa T, Castorena CM, Pearson M, Kusminski CM, Ahmed N, Battiprolu PK, Kim KW, Lee S, Hill JA, Scherer PE, Holland WL, Elmquist JK. SF-1 expression in the hypothalamus is required for beneficial metabolic effects of exercise. eLife. 2016; 5. PMID: 27874828
Fujikawa, T. *, and Coppari, R. *, Living without insulin: the role of leptin signaling in the hypothalamus. Front Neurosci, (2015) 9, 108. *co-corresponding author Williams, K.W., Liu, T., Kong, X., Fukuda, M., Deng, Y., Berglund, E.D., Deng, Z., Gao, Y., Liu, T., Sohn, J.-W., Jia, L., Fujikawa, T., Kohno, D., Sccotte, M., Lee, S., Lee, S., Sun, K., Chang, Y., Scherer, P.E., and Elmquist, J.K., Xbp1s in Pomc neurons connects ER stress with energy balance and glucose homeostasis. Cell metabolism, (2014) 20, 471-482.