Response of Hepatic Microbodies to a Hypolipidemic Agent, Ethyl Chlorophenoxyisobutyrate (cpib)

Current knowledge regarding the origin of microbodies, their function in cell metabolism, the manner in which they are destroyed or disposed of by the cell, and their responses to pathological conditions is limited, but emerging information concerning their chemical composition (1, 2), the structure and content of their nucleoid (1, 3-5), and their possible relationship to other cell organelles (6, 7) provides a stimulating and useful background for further investigation. Though a limited range of alteration in the number or structure of microbodies has been described, these organelles, compared to other cell constituents, appear relatively indolent and unresponsive to most experimental manipulations. Accordingly, new information relating their morphologic and biochemical responses to specific metabolic stimuli may prove useful for further studies. Current experiments in our laboratories have revealed conspicuous numerical and ultrastrucrural changes in microbodies following administration of a hypolipidemic agent (ethyl chlorophenoxyisobutyrate, CPIB) capable of lowering serum lipid levels in man (8, 9) and in experimental animals (10). The observations, though preliminary, provide strong support for the proposal of Novikoff and Shin (7) that microbodies are related to lipid metabolism because the structural changes are accompanied by a decrease in liver cholesterol and triglyceride levels, and an increase in liver catalase activity and weight. Concomitantly, a slight increase in liver protein and phospholipid occurs (11, 12). Two electron microscope studies of rat liver following CPIB treatment have been reported. Paget (13) described an increase in size and number of mitochondria and the formation of "giant lysosomes" of uncertain identity. The second report (14) related the effects of CPIB treatment to numerical changes in microbodies and to enzyme activity in rat liver, but neither alterations of the matrix nor other changes in fine structure of microbodies were described. M A T E R I A L A N D M E T H O D S