Dietary Fat Interacts with PCBs to Induce Changes in Lipid Metabolism in Mice Deficient in Low-Density Lipoprotein Receptor

Abstract

There is evidence that dietary fat can modify the cytotoxicity of polychlorinated biphenyls (PCBs) and that coplanar PCBs can induce inflammatory processes critical in the pathology of vascular diseases. To test the hypothesis that the interaction of PCBs with dietary fat is dependent on the type of fat, low-density lipoprotein receptor–deficient (LDL-R−/−) mice were fed diets enriched with either olive oil or corn oil for 4 weeks. Half of the animals from each group were injected with PCB-77. Vascular cell adhesion molecule-1 (VCAM-1) expression in aortic arches was non-detectable in the olive-oil–fed mice but was highly expressed in the presence of PCB-77. PCB treatment increased liver neutral lipids and decreased serum fatty acid levels only in mice fed the corn-oil–enriched diet. PCB treatment increased mRNA expression of genes involved in inflammation, apoptosis, and oxidative stress in all mice. Upon PCB treatment, mice in both olive- and corn-oil–diet groups showed induction of genes involved in fatty acid degradation but with up-regulation of different key enzymes. Genes involved in fatty acid synthesis were reduced only upon PCB treatment in corn-oil–fed mice, whereas lipid transport/export genes were altered in olive-oil–fed mice. These data suggest that dietary fat can modify changes in lipid metabolism induced by PCBs in serum and tissues. These findings have implications for understanding the interactions of nutrients with environmental contaminants on the pathology of inflammatory diseases such as atherosclerosis.

Changing ratios of omega-6 to omega-3 fatty acids can differentially modulate polychlorinated biphenyl toxicity in endothelial cells

“…Furthermore, coplanar PCBs can suppress delta 5 and 6 desaturase activities, thus disrupting the synthesis of fatty acid precursors for eicosanoid metabolism [17]. Our own data from plasma and livers of LDL receptor-deficient mice support the hypothesis that treatment with PCBs can facilitate clearance of linoleic acid from plasma into vascular tissues [18]. Such a change in lipid milieu could exacerbate fatty acid-and/or PCB-induced oxidative stress and a vascular inflammatory response.…”

Lipid Adjustment in the Analysis of Environmental Contaminants and Human Health Risks

“…Investigators typically have insufficient biologic information to specify the correct analytic model, often resulting in analytic strategies based on unverified assumptions. For example, research indicates a possible causal effect of PCBs on serum lipid levels (Hennig et al 2005; Langer et al 2003). Additionally, lipid levels have been suggested to affect breast cancer risk (Atalay et al 2004), but their impact on other health end points has received limited attention.…”

Hepatocellular carcinoma and the risk of occupational exposure

“…Other studies in workers exposed to the PCB have reported an increased incidence of liver tumors [185][186][187][188] . Some possible mechanisms by which PCB can cause cancer have been assumed: Reactive oxygen species (ROS) is produced through the enzymatic oxidation or autoxidation of PCB; PCB determines the increased expression of genes responsible for inflammation and apoptosis in the liver; and PCB has "toxic" effects on certain genes, such as the loss of part of a chromosome and chromosome breakage [189][190][191][192][193][194][195][196][197][198][199] . ROS are also able to reduce telomerase activity which can determine telomere shortening.…”