Liver expression of the nuclear hormone receptors PPAR, LXR, and RXR and blood parameters of lipid and carbohydrate metabolism in strains of mice susceptible and resistant to hepatocarcinogenesis

Abstract

Earlier it was shown that male mice of the DD/He strain were highly susceptible to ortho-aminoa-zotoluene (OAT) induced hepatocarcinogenesis, and resistant to spontaneous liver tumor development as compared to male mice of the CC57BR/Mv strain. In the present work we have made a comparative investigation of peroxisome proliferator-activated receptor (PPAR), liver X-receptor (LXR) and retinoic X-receptor (RXR) mRNA levels in liver as well as concentrations of corticosterone, glucose, lipids and insulin in blood of male DD/He and CC57BR/Mv mice. Using the multiplex RT-PCR method it was found that PPAR-α, PPAR-γ, RXR-α, and RXR-β mRNA content was significantly lower in the liver of DD mice than in CC57BR mice. No significant interstrain differences were found in the content of LXR-α and LXR-β mRNA. In DD mice there was more than the 3-fold decrease of blood content of corticosterone (involved in PPAR and RXR regulation). DD mice demonstrated a significant decrease in blood serum glucose and insulin concentrations as well as higher reactivity to insulin as compared with NN57BR mice. Elevated blood total cholesterol and HDL cholesterol levels were found in DD mice whereas triglyceride content was basically the same in both mouse strains. It is known that glucocorticoids, PPAR and RXR play crucial role in transcription regulation of the inflammation response. Therefore our data on decreased corticosterone level in blood, PPAR and RXR mRNA content in the liver of the DD suggest that sensitivity of this strain of mice to the development of OAT-induced hepatocarcinomas may be associated with increased inflammatory reaction to this carcinogen.