The role of apolipoprotein A-IV in food intake regulation

Apolipoprotein (apo) A-IV is a glycoprotein synthesized by the human intest ine. In rodents, both the small intestine and the liver secrete apo A-IV; t he small intestine, however, is by far 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 reesterif ication of fatty acids to form triglycerides. Rather, it is the formation o f chylomicrons that acts as a signal for the induction of intestinal apo A- IV synthesis. Intestinal apo A-IV synthesis is also enhanced by a factor fr om the ileum and that factor is probably peptide tyrosine-tyrosine (PYY). T he inhibition of food intake by apo A-IV is probably mediated centrally. Th e stimulation of intestinal synthesis and secretion of apo A-IV by lipid ab sorption are rapid; thus, apo A-IV likely plays a role in the short-term re gulation of food intake. Other evidence suggests that apo A-IV may also be involved in the longterm regulation of food intake and body weight. Chronic ingestion of a high fat diet blunts the intestinal apo A-IV response to li pid feeding and may explain why the chronic ingestion of a high fat diet pr edisposes both animals and humans to obesity.