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Differential effects of fibrates on the acyl composition of microsomal phospholipids in rats
Author(s) -
Vázquez Manuel,
Muñoz Sonia,
Alegret Marta,
Adzet Tomás,
Merlos Manuel,
Laguna Juan C.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb16413.x
Subject(s) - chemistry , phosphatidylethanolamine , phosphatidylcholine , arachidonic acid , gemfibrozil , bezafibrate , docosapentaenoic acid , medicine , endocrinology , biochemistry , polyunsaturated fatty acid , linoleic acid , phospholipid , docosahexaenoic acid , fatty acid , biology , cholesterol , enzyme , membrane
1 The time‐course and comparative effects of treatment with clofibrate (CFB), bezafibrate (BFB), and gemfibrozil (GFB) on the acyl composition of the main microsomal phospholipids, i.e. phosphatidylchoβ line and phosphatidylethanolamine, have been studied in male Sprague‐Dawley rats. 2 The administration of the three fibrates caused a strong peroxisomal induction and a hypolipidaemic effect. Concerning the changes in acyl composition, CFB and BFB behaved in a similar way, with differences which could be attributed to their different potency as peroxisome inducers, whereas GFB showed a somewhat distinct profile. 3 The three drugs increased the relative content of palmitic, palmitoleic and oleic acids, whereas the levels of stearic acid and also those of long chain, highly unsaturated fatty acids docosatetraenoic, docosapentaenoic and docosahexaenoic acids were reduced. In general, these effects appeared from the first day of treatment and were highly correlated with peroxisomal proliferation. In addition, they were more evident in the phosphatidylcholine than in the phosphatidylethanolamine fraction. 4 Fibrates increased total monounsaturated fatty acids, whereas a decrease in total polyunsaturated fatty acids in the phosphatidylcholine fraction was observed in CFB‐ and BFB‐, but not in GFB‐treated rats. Clear differences appeared between CFB and BFB on the one hand, and GFB on the other when the influence of fibrate treatment on the molar percentages of linoleic, eicosatrienoic, arachidonic and mead acids was analyzed. 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 both fractions and arachidonic acid in phosphatidylethanolamine, whereas 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 activities related to fatty acid chain modelling, particularly elongases and desaturases.