Endotoxin-induced alterations of lipid and fatty acid compositions in rat liver peroxisomes

The structure/function of peroxisomal lipids in rat liver treated with a su blethal dose of endotoxin, a lipopolysaccharide (LPS), was investigated. Pe roxisomes isolated from LPS-treated rat liver had remarkable alterations in lipid content compared with saline treated control liver peroxisomes. Chol esterol and phospholipids (PL) decreased significantly by 28.7% and 50.8%, respectively, leading to the change in the ratio of cholesterol/phospholipi ds (control 0.081 versus LPS 0.118, P <0.001). A quantitative analysis from LPS-treated rat liver peroxisomes showed a general decrease in all classes of PL. No such alterations were observed in lipid content of other subcell ular organelles. The peroxisomal fatty acid composition in LPS-treated anim als was also altered. An analysis of fatty acid composition in PL and phosp hatidylcholine from LPS-treated peroxisomes showed an increase in arachidon ic acid (C20:4) and docosahexaenoic acid (C22:6). Very long chain (VLC) fat ty acids (>C22:0) were also found increased in all classes of lipids in LPS -treated peroxisomes. Gadolinium chloride (GAD) mediated inactivation of Ku pffer cells (KC) normalized cholesterol/PL ratio in LPS-treated peroxisomes . Collectively, the results indicate that the peroxisome metabolism of lipi ds and fatty acids is specifically altered in endotoxin-treated rat liver a nd at least part of the alterations may be mediated by factors released by KC.