Research Projects

Skeletal muscle energy expenditure (EE) could be a potential protection against metabolic disorders like type 2 diabetes. Studies have shown that skeletal muscle-specific over-expression of sarcolipin (SLN) increases EE by interacting with sarco(endo)plasmic reticulum calcium ATPase (SERCA). This interaction could be targeted pharmacologically to enhance EE as a strategy to restore skeletal muscle health and counter metabolic disorders. However, pharmacological agents targeting skeletal muscle metabolism have not yet reached clinical trials. Capsaicin (CAP), a natural product found in red chili peppers, has metabolic modulating effects and has been found to enhance SLN binding to SERCA. CAP binds at the SLN-SERCA interface through strong non-covalent interactions, forming a high affinity complex. The researchers propose a re-iterative approach based on cell biological evaluation and molecular modeling to achieve a promising SLN enhancer candidate. The main experiments will involve SERCA/SLN modeling, chemical synthesis, purification, and spectroscopic characterization of new compounds, measuring glucose uptake in muscle cells, measuring SERCA activity, measuring metabolic rate, and analyzing serum glucose levels in induced diabetes mice. This proposal will establish a novel concept and create an exciting new area of research in diabetes treatment.