Hepatic RNA Metabolism in Male and Female Obese Rats Fed Cholesterol

Abstract

DNA-dependent RNA polymerase activity was studied in liver nuclei from genetically lean or obese rats of the Zucker strain (males and females). Two recommended and modified assay procedures were adopted: a conventional Mg++-dependent system (I); and an Mn++-dependent-(NH4)2SO4-stimulated system (II). Assays were carried out in liver nuclear fractions from rats fed either a control purified diet or a standardized cholesterol-containing diet. Liver nuclei from obese rats had higher levels of polymerase activity by either assay procedure; the activity measured in nuclear material derived from females (of either genotype) was consistently higher than those from males. However, cholesterol feeding resulted in a depression of nuclear RNA polymerase activity in obese and lean rats of both sexes only when method I was used, suggesting that this depression (which also reflects changes in microsomal protein synthesis) may be more closely related to ribosomal RNA synthesis. An examination of RNA synthesis in vivo generally supported these findings. Using 14C-orotic acid, it was shown that the greatest percentage decrease was associated with a crude nucleolar fraction.