The role of apolipoprotein A-IV in the regulation of food intake.

Apolipoprotein A-IV (apo A-IV) is a glycoprotein synthesized by the human intestine. In rodents, both the small intestine and liver secrete apo A-IV, but the small intestine is the major organ responsible for the circulating apo A-IV. Intestinal apo A-IV synthesis is markedly stimulated by fat absorption and appears not to be mediated by the uptake or reesterification of fatty acids to form triglycerides. Rather, the formation of chylomicrons acts as a signal for the induction of intestinal apo A-IV synthesis. Intestinal apo A-IV synthesis is also enhanced by a factor from the ileum, probably peptide tyrosine-tyrosine. The inhibition of food intake by apo A-IV is mediated centrally. The stimulation of intestinal synthesis and the secretion of apo A-IV by lipid absorption are rapid; thus, apo A-IV likely plays a role in the short-term regulation of food intake. Other evidence suggests that apo A-IV may also be involved in the long-term regulation of food intake and body weight. Chronic ingestion of a high-fat diet blunts the intestinal apo A-IV response to lipid feeding and may explain why the chronic ingestion of a high-fat diet predisposes both animals and humans to obesity.