Grant: Project Grant

Obesity is a serious health problem in Canada. Obesity is often accompanied by increased fat deposition in liver and intestine (and other cells and organs), which consequently leads to decreased action of a hormone called insulin. When insulin does not work well in liver and intestine, these organs increase production of particles that carry "bad" cholesterol in blood and cause heart disease and stroke. The amount of fat in liver and intestine is determined by fat production, fat breakdown (process called lipolysis) and fat export out of these organs. Lipolysis is carried out by proteins called lipases. We are researching one of these lipases called arylacetamide deacetylase (AADAC), which is present only in liver and small intestine. We are proposing experiments that will show that AADAC decreases fat levels in liver and intestine and therefore also the production of particles carrying "bad" cholesterol. AADAC might also metabolize certain drugs, including flutamide. Flutamide is used in treatment of cancer and polycystic ovarian syndrome and hence it is important to determine whether AADAC is indeed responsible for the harmful side effects in patients taking this drug. We have developed technology that will allow us to determine the importance of AADAC in fat and drug metabolism. This research will not only advance health-related knowledge but because deletions of AADAC gene in humans have been reported, this preclinical research program is expected to have tangible application for health care.