Inhibition of lipid synthesis by clofibrate: comparative study of human skin, rat skin, and rat liver in vitro.
The effects of clofibrate (ethyl p-chlorophenoxyisobutyrate) on lipid synthesis by human skin were studied in vitro. The drug was found to inhibit lipid synthesis from [1-(14)C]acetate or [U-(14)C]glucose. While the synthesis of all classes of lipids was suppressed, inhibition of sterol synthesis was more pronounced than that of fatty acids and glycerides. By comparison, sodium p-chlorophenoxyisobutyrate was less effective as an inhibitor. The addition of glucose to the incubation medium enhanced lipid synthesis from both [1-(14)C]acetate and [U-(14)C]glucose. The inhibitory effect of clofibrate could be partially reversed by increasing the glucose concentration in the incubation medium. Rat skin and rat liver were studied similarly, using [1-(14)C]-acetate as a tracer for lipid synthesis, and the inhibitory effect of clofibrate was also demonstrated. Of the three tissues studied, human skin was the most sensitive to the drug and yielded more reproducible results.
D000085:Acetates / Q000378:metabolism; D000818:Animals; D002247:Carbon Isotopes; D002845:Chromatography; D002850:Chromatography, Gel; D002855:Chromatography, Thin Layer; D002994:Clofibrate / Q000494:pharmacology*; D003864:Depression, Chemical; D005227:Fatty Acids / Q000096:biosynthesis; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D005989:Glycerides / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D012867:Skin / Q000187:drug effects*; D012964:Sodium / Q000494:pharmacology; D013045:Species Specificity; D013261:Sterols / Q000096:biosynthesis; D014280:Triglycerides / Q000096:biosynthesis
D000085:Acetates; D002247:Carbon Isotopes; D005227:Fatty Acids; D005989:Glycerides; D008055:Lipids; D013261:Sterols; D014280:Triglycerides; D012964:Sodium; D002994:Clofibrate; D005947:Glucose