Dietary conjugated linoleic acid induces peroxisome-specific enzyme accumulation and ornithine decarboxylase activity in mouse liver

Abstract

Previous studies have shown that the dietary fatty acids, conjugated linoleic acids (CLA), inhibit carcinogenesis in the colon, mammary gland, forestomach, and skin. Several properties of this chemoprotective polyunsaturated fatty acid suggest it will act as an hepatic peroxisome proliferator. This study evaluated the effect of dietary CLA on the accumulation of enzymes associated with peroxisome proliferation in rodent liver. Female SENCAR mice were fed one of four semipurified diets containing 5% corn oil without CLA (“control diet”) or supplemented with incremental levels of CLA (0.5%, 1.0% or 1.5% by weight of diets) for 6 weeks. Hepatic mRNA levels of several enzymes known to be induced during peroxisome proliferation [i.e., acyl-CoA oxidase (ACO), cytochrome P4504A1 (CYP4A1), and liver fatty acid binding protein (FABP)] were measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Diets containing 0.5%, 1.0% or 1.5% CLA were associated with approximately 6-, 9-, and 9-fold increases in ACO mRNA, respectively, compared with mRNA levels in mice fed the control diet. The steady state levels of FABP and CYP4A1 mRNA accumulation were maximal in animals fed 1.0% CLA diets and less magnified in mice fed 1.5% CLA diets. Western blot analysis revealed that the relative abundance of ACO protein in livers of mice fed CLA-containing diet groups (0.5%, 1.0%, and 1.5% CLA) were 2.5, 3.0, and 3.0 times the level ACO protein of mice fed the control diet (0.0% CLA). Because most peroxisome proliferators are considered nongenotoxic hepatocarcinogens in rodents, the effect of dietary CLA on ornithine decarboxylase (ODC) activity, a measure of cell proliferation and tumor promotion, was quantified. Activity on hepatic ODC was increased by approximately 10-fold for mice fed 1.0% and 1.5% diets, respectively, compared with those fed the control or 0.5% CLA diets. These data suggest that CLA displays the typical peroxisome proliferation response, i.e., induction of ACO, CYP4A1 and FABP accumulation and cell proliferation in rodent liver.