It is accepted that cancer development is associated with metabolic changes. Previously, we established a model of hepatic preneoplasia in which adult rats were subjected to a 2-phase model of hepatocarcinogenesis (initiated-promoted, IP) for 6weeks until they develop altered hepatic foci (AHF). Here, 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. We found that carboxylesterase 3/triacylglycerol hydrolase (Ces3/Tgh) presented with a perilobular distribution surrounding lipid droplets in normal livers. However, 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. These studies show a preventive role of Ces3/Tgh in liver cancer development.
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Highlights Vitamin K2 blocks IFN-α-2b-induced reduction in size and volume of the altered hepatic foci in rats Vitamin K2 inhibits IFN-α-2b-induced apoptosis in rat preneoplastic livers Vitamin K2 inhibition of IFN-α-2b-induced apoptosis is mediated by increased levels of total hepatic Bcl-2 in rat preneoplastic livers
The present work provides novel data concerning the preventive actions of glycerol during the development of liver cancer and represents an economically feasible intervention to treat high-risk individuals.
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