Control of Synthesis and Secretion of Intestinal Apolipoprotein A-IV by Lipid

Abstract

Apolipoprotein (apo) A-IV, a component of intestinally secreted, triacylglycerol-rich lipoproteins, has recently been proposed as a physiological controller of gastric function and food intake. Thus, it is important to understand the mechanisms involved in the control of expression, synthesis and secretion of apo A-IV. Apo A-IV is a member of a closely linked, multigene cluster which includes apolipoproteins A-I and C-III. Expression and synthesis of apo A-IV display marked variability with regard to species, tissue, stage of development and response to hormones, but intestinal apo A-IV is consistently stimulated by dietary lipid. The precise molecular mechanisms underlying the response of apo A-IV to lipid have not been clearly defined. Most evidence supports the hypothesis that some aspect of lipid transport is necessary for the apo A-IV response, but only part of this response may be due to a direct effect of intestinal lipid: recent findings suggest a connection between intestinal production of apo A-IV and hormonal and/or neural factors associated with operation of the "ileal brake." Thus, apo A-IV may play an integrative role in the modulation of both upper gastrointestinal function and ingestive behavior.