Major clofibrate effects on liver and plasma lipids are independent of changes in polyunsaturated fatty acid composition induced by dietary fat

The effects of clofibrate on the content and composition of liver and plasm a lipids was studied in mice fed for 4 wk on diets enriched in n-6 or n-3 p olyunsaturated fatty acids (PUFA) from sunflower oil (SO) or fish oil (FO), respectively; both oils were fed at 9% of the diet (dry weight basis). Onl y FO was hypolipidemic. Both oil regimes led to slightly increased concentr ations of phospholipids (PL) and triacylglycerols (TC) in liver as compared with a standard chow diet containing 2% fat. Clofibrate promoted hypolipid emia only in animals fed SO. Its main effect was to enlarge the liver, such growth increasing the amounts of major glycerophospholipids while depletin g the TC. SO and FO consumption changed the proportion of n-6 or n-3 PUFA i n liver and plasma lipids in opposite ways. After clofibrate action, the PU FA of liver PL were preserved better than in the absence of oil supplementa tion. However, most of the drug-induced changes (e.g., increased 18:1n-9 an d 20:3n-6, decreased 22:6/20:5 ratios) occurred irrespective of lipids bein g rich in n-6 or n-3 PUFA. The concentration of sphingomyelin (SM), a minor liver lipid that virtually lacks PUFA, increased with the dietary oils, de creased with clofibrate, and changed its fatty acid composition in both sit uations. Thus, oil-increased SM had more 22:0 and 24.0 than clofibrate-decr eased SM, which was significantly richer in 22:1 and 24:1.