| The work presented here has displayed the problems associated with liver steatosis in the setting of transplantation and ischemia/reperfusion. We have identified new and more accurate ways to determine the total amount of steatosis as well as its fatty acid components. By better understanding the makeup of steatosis, we were able to develop ways to increase the use of these steatotic livers for transplantation. The use of monoclonal antibodies against lipopolysaccharide (anti-DCLA and anti-J5) determined that indeed LPS is a major component in ischemia/reperfusion injury with bowel congestion following a transplant. To better understand the mechanistic role of the anti-LPS monoclonal antibodies employed to protect the liver from LPS, we began to determine the LPS receptors (TLR4) role in I/R injury. We found that the steatotic animals had higher levels of TLR4 than lean livers, which possibly implicated TLR4 expression in the outcome of steatotic livers following transplant. This work also explored the role of fatty acid synthase inhibition in decreasing liver steatosis. The aim used epigallocatechin gallate (EGCG), a green tea flavonoid and fatty acid synthase inhibitor as a short-term treatment of liver steatosis. We determined that EGCG decreased liver steatosis and reduced liver injury following I/R with bowel congestion. The results have shown that EGCG and anti-LPS antibodies have a possible role to protect transplant patients from PNF following I/R. Ultimately, the hope is that these therapeutics may someday play a role in the clinical setting, taking the research from the bench top to the bedside. |
