DIETARY CONJUGATED LINOLEIC-ACID INDUCES PEROXISOME-SPECIFIC ENZYME ACCUMULATION AND ORNITHINE DECARBOXYLASE ACTIVITY IN MOUSE-LIVER

Previous studies have shown that the dietary fatty acids, conjugated l inoleic acids, (CLA), inhibit carcinogenesis in the colon, mammary gla nd, forestomach, and skin. Several properties of this chemoprotective polyunsaturated fatty acid suggest it will act as an hepatic peroxisom e proliferator. This study evaluated the effect of dietary CLA on the accumulation of enzymes associated with peroxisome proliferation in ro dent 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 indu ced during peroxisome proliferation [i.e., acyl-CoA oxidase (ACO), cyt ochrome P4504A1 (CYP4A1), and live fatty acid binding protein (FABP)] were measured by quantitative reverse transcriptase-polymerase chain r eaction (RT-PCR). Diets containing 0.5%, 1.0% or 1.5% CLA were associa ted with approximately 6-, 9-, and 9-fold increases in ACO mRNA, respe ctively, compared with mRNA levels in mice fed the control diet. The s teady state levels of FABP and CYP4A1 mRNA accumulation were maximal i n animals fed 1.0% CLA diets and less magnified in mice fed 1.5% CLA d iets. Western blot analysis revealed that the relative abundance of AC O protein in livers of mice fed CLA-containing diet groups (0.0% CLA). Because most peroxisome proliferators are considered nongenotoxic hep atocarcinogens in rodents, the effect of dietary CLA on ornithine deca rboxylase (ODC) activity, a measure of cell proliferation and tumor pr omotion, was quantified. Activity of hepatic ODC was increased by appr oximately 10-fold for mice fed 1.0% and 1.5% diets, respectively, comp ared 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. (C) 1997 Elsevier Science Inc. 1997.