The participation of ethyl 4-benzyloxybenzoate (BRL 10894) and other aryl-substituted acids in glycerolipid metabolism.

Investigation into the mechanism of action of BRL 10894 (ethyl 4-benzyloxybenzoate), a compound possessing hypolipidemic activity in the rat, disclosed participation in glycerolipid metabolism. In the presence of BRL 10894, an abnormal metabolite was synthesized in vitro using liver slices or rings of small intestine with glycerol, palmitate, or monoolein as substrate, and using adipose tissue with pyruvate as substrate. Esters related chemically to BRL 10894 and other pharmacologically active acids (e.g., ibuprofen) also produced abnormal metabolites in vitro. With BRL 10894 in the diet, a similar metabolite was produced in vivo in rats and accumulated in adipose tissue. Chemical characterization of the material synthesized in vivo showed that the metabolite was a triglyceride in which one fatty acid moiety was substituted by the acid of BRL 10894. Additional proof of this structure was obtained by comparison with reference material synthesized in our laboratories. The study of the initimate involvement of exogenous acids in glycerolipid turnover is of value in the characterization of pharmacologically important acids and may be of use in achieving a greater understanding of certain aspects of lipid metabolism.