DIFFERENTIAL-EFFECTS OF FIBRATES ON THE ACYL COMPOSITION OF MICROSOMAL PHOSPHOLIPIDS IN RATS

1 The time-course and comparative effects of treatment with clofibrate (CFB), bezafibrate (BFB), and gemfibrozil (GFB) on the acyl compositi on of the main microsomal phospholipids, i.e, phosphatidylcholine and phosphatidylethanolamine, have been studied in male Sprague-Dawley rat s. 2 The administration of the three fibrates caused a strong peroxiso mal induction and a hypolipidaemic effect. Concerning the changes in a cyl composition, CFB and BFB behaved in a similar way, with difference s which could be attributed to their different potency as peroxisome i nducers, whereas GFB showed a somewhat distinct profile. 3 The three d rugs increased the relative content of palmitic, palmitoleic and oleic acids, whereas the levels of stearic acid and also those of long chai n, highly unsaturated fatty acids docosatetraenoic, docosapentaenoic a nd docosahexaenoic acids were reduced. In general, these effects appea red from the first day of treatment and were highly correlated with pe roxisomal proliferation. In addition, they were more evident in the ph osphatidylcholine than in the phosphatidylethanolamine fraction. 4 Fib rates increased total monounsaturated fatty acids, whereas a decrease in total polyunsaturated fatty acids in the phosphatidylcholine fracti on was observed in CFB- and BFB-, but not in GFB-treated rats. Clear d ifferences appeared between CFB and BFB on the one hand, and GFB on th e other when the influence of fibrate treatment on the molar percentag es of linoleic, eicosatrienoic, arachidonic and mead acids was analyze d. 5 GFB increased linoleic acid content in phosphatidylethanolamine, whereas CFB and BFB decreased its level in both phospholipid fractions . In contrast, CFB and BFB enhanced eicosatrienoic and mead acids in b oth fractions and arachidonic acid in phosphatidylethanolamine, wherea s GFB had practically no effect. 6 The different behaviour of GFB may be explained on the basis of two different observations. First, GFB is the weakest peroxisomal inducer of the three fibrates tested. Second, GFB is the strongest inhibitor in vitro of some of the enzyme activit ies related to fatty acid chain modelling, particularly elongases and desaturases.