Altered Lipid Parameters in Hepatic Subcellular Membrane Fractions Induced by Fumonisin B1

Abstract  Alteration of lipid constituents of cellular membranes has been proposed as a possible mechanism for cancer promotion by fumonisin B1 (FB1). To further investigate this hypothesis a dietary dosage which initiates and promotes liver cancer (250 mg FB1/kg) was fed to male Fischer rats for 21 days and the lipid composition of plasma, microsomal, mitochondrial and nuclear subcellular fractions determined. The effect of FB1 on the cholesterol, phosphatidylcholine (PC) and phosphatidylethanolamine (PE), as well as sphingomyelin (SM) and the phospholipids-associated fatty acid (FA) profiles, were unique for each subcellular membrane fraction. PE was significantly increased in the microsomal, mitochondrial and plasma membrane fractions, whereas cholesterol was increased in both the microsomal and nuclear fraction. In addition SM was decreased and increased in the mitochondrial and nuclear fractions, respectively. The decreased PC/PE and polyunsaturated/saturated (P/S) FA ratio in the different membrane fractions suggest a more rigid membrane structure. The decreased levels in polyunsaturated fatty acids in PC together with a pronounced increase in C18:1ω9 and C18:2ω6 were indicative of an impaired delta-6 desaturase. The increased ω6/ω3 ratio and decreased C20:4ω6 PC/PE ratio due to an increase in C20:4ω6 in PE relatively to PC in the different subcellular fractions suggests a shift towards prostanoid synthesis of the E2 series. Changes in the PE and C20:4ω6 parameters in the plasma membrane could alter key growth regulatory and/or other cell receptors in lipid rafts known to be altered by FB1. An interactive role between C20:4ω6 and ceramide in the mitochondria, is suggested to regulate the balance between proliferation and apoptosis in altered initiated hepatocytes resulting in their selective outgrowth during cancer promotion effected by FB1.