HEPATIC CES3/TGH IS DOWNREGULATED IN THE EARLY STAGES OF LIVER CANCER DEVELOPMENT IN THE RAT

COMANZO, CG; CEBALLOS, MP; PARODY, JP; LORENZETTI, MF; PISANI, GB; RONCO, MT; ALVAREZ ML; CARRILLO, MC; QUIROGA, AD

Congreso; LII Reunión Anual de SAIB 2016; 2016

Cancer development is associated with metabolic changes. We have previously established a model of hepatic preneoplasia in which adult rats were subjected to a 2-phase model of hepatocarcinogenesis (initiated-promoted, IP) for 6 weeks until they develop altered hepatic foci (AHF). Objectives: to study lipid metabolism and the role of carboxylesterase 3/triacylglycerol hydrolase (Ces3/Tgh) in the early stages of liver cancer development. Results: we found that a whole metabolic shift occurs in order to favor cancer development. IP animals presented with increased plasma lipids due to increased VLDL secretion as well as increased liver lipid accretion due to stimulated transacetylase activity rather than lipogenesis, compared to control rats. Ces3/Tgh presented with a perilobular distribution surrounding lipid droplets in normal livers. It is downregulated both at the protein and mRNA level in liver homogenates and is almost undetectable inside the AHF with no changes in the surrounding tissue. Ces3/Tgh expression is regulated by ω-3 fatty acids, thus, supplementation of diet with fish oil, allowed the restoration of Ces3/Tgh expression inside the foci and, more interestingly, led to the decrease in number and volume of the AHF. Conclusions: these studies show a preventive role of Ces3/Tgh in liver cancer development.