The effect of fatty-acid synthase inhibitor on PPAR-r and UCPZ, expression during steatotic liver ischemia reperfusion. (South Carolina Academy of Sciences Abstracts).

The transcription factor Peroxisome Proliferator Activated Receptor [gamma] has been shown to he involved in a variety of physiological processes including adipocyte differentiation, fat storage, inflammatory response, and insulin sensitization in liver and muscle tissue. Problems such as Kupffer cell dysfunction, microcirculatory changes, ATP depletion, the generation of reactive oxygen species, and increased leukocyte adhesion resulting from the ischemia reperfusion period of the liver transplantation sometimes lead to graft failure or primary nonfunction of the liver. These problems are more exaggerated in people with clinical obesity. Current studies show that the mechanisms by which steatotic livers are more susceptible are related to an increased sensitivity to endotoxin and high levels of uncoupling protein 2 at baseline. Cerulenin is an antibiotic that is effective at inhibiting the passage of fatty acids from the cytoplasm to the mitochondria. It is our hypothesis that decreasing the amount of free fatty acids, which are PPAR [gamma] agonists, may result in a decrease in UCP2 and PPAR [gamma] expression in murine hepatocytes. This study seeks to show a relationship between PPAR [gamma] expression and obesity by analyzing the total RNA content of isolated murine hepatic tissue that has been exposed to ischemia reperfusion injury to detect changes in the regulation PPAR [gamma] and UCP2.

John Lucas
Department of Biology, Erskine College
Stephen Shafizadeh, Kenneth Chavin
Division of Transplant Surgery, Medical University of South Carolina