Gene expression modulation of rat liver cholesterol metabolism by oleoyl-estrone

Abstract

Since oleoyl-estrone (OE) decreases circulating cholesterol in the rat, we analyzed the response to OE treatment of hepatic gene expressions related with cholesterol metabolism. Male overweight rats treated with oral OE (10 nmol/g daily) were compared with a pair-fed (PF) group and controls fed ad libitum. Serum parameters and liver lipid and cholesterol contents were measured. Total tissue RNA was used for real-time PCR analysis of the gene expression of enzymes and regulatory factors of liver cholesterol metabolism. Cholesterol-7α-hydroxylase and ABC transporter A1 protein levels were estimated by Western blot. Pair-feeding and OE treatment reduced the expression of 3-hydroxy-3-methyl-glutaryl-CoA synthase. OE increased the expression of the LDL receptor. Cholesterol disposal, through bile acids synthesis, was increased in PF and more markedly in OE rats. Gene expressions of the ABC transporter A1 and apolipoproteins A1 and E were increased in OE rats. The expression of liver X receptor was lower in PF than in OE and controls. The rapid disappearance of circulating cholesterol elicited by OE is consequence of: (1) decreased mevalonate pathway activity, (2) a higher expression of the LDL-receptor, and (3) the activation of the oxidation of cholesterol to form bile acids as a consequence of the higher cholesterol concentrations found in liver, also affected by energy availability.