title: Hepatic carboxylesterase 3 (Ces3/Tgh) is downregulated in the early stages of liver cancer development in the rat.
abstract: 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.
authors: Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina; Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario, Argentina. Electronic address: quiroga@ifise-conicet.gov.ar.
authors: Ariel D
authors: AD
authors: Quiroga
authors: Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina. Electronic address: ceballos@ifise-conicet.gov.ar.
authors: María P
authors: MP
authors: Ceballos
authors: Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina. Electronic address: parody@ifise-conicet.gov.ar.
authors: Juan P
authors: JP
authors: Parody
authors: Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina. Electronic address: cgcomanzo@gmail.com.
authors: Carla G
authors: CG
authors: Comanzo
authors: Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina. Electronic address: lorenzetti@ifise-conicet.gov.ar.
authors: Florencia
authors: F
authors: Lorenzetti
authors: Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario, Argentina. Electronic address: gpisani@fbioyf.unr.edu.ar.
authors: Gerardo B
authors: GB
authors: Pisani
authors: Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina. Electronic address: ronco@ifise-conicet.gov.ar.
authors: María T
authors: MT
authors: Ronco
authors: Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina; Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario, Argentina. Electronic address: alvarez@ifise-conicet.gov.ar.
authors: María de L
authors: ML
authors: Alvarez
authors: Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina; Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario, Argentina. Electronic address: carrillo@ifise-conicet.gov.ar.
authors: María C
authors: MC
authors: Carrillo
keywords: Carboxylesterases; Hypertriglyceridemia; Lipid metabolism; Liver preneoplasia; Polyunsaturated fatty acids; Rat