ABSTRACT
This chapter proposes to review our knowledge concerning the effect of fat-soluble xenobiotics on the ability of the intestine to synthesize and secrete lipids and lipoproteins. Intestinal tissue in man and experimental animals has a wide variety of metabolic capabilities which are associated with maintaining the integrity of the tissue and with performing the functions of nutrient absorption and transport. Chylomicrons are synthesized during fat absorption and are the principal transport vehicle for the transference of exogenous lipid from the intestinal lumen to the blood circulation via the lymphatic system. Inhibition of triglyceride synthesis in rat intestinal mucosa has been demonstrated both in vivo and in vitro with the anorexic compound, fenfluramine; in this case inhibition appears to result from inhibition of fatty acylCoA transfer to monoglyceride by monoacylglycerol acyltransferase. The significance of intestinal apoprotein synthesis to lipid transport was evident in patients with abetalipoproteinemia and has since been demonstrated in animal models with protein synthesis inhibitors such as puromycin.
