The focus of this article is to review evidence that
apolipoprotein A-IV (
apo A-IV) acts as a satiety factor. Additionally, information regarding the general involvement of
apo A-IV in the regulation of food intake and
body weight is stated.
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 circulating
apo A-IV. There is now solid evidence that the hypothalamus, especially the arcuate nucleus, is another active site of
apo A-IV expression. Intestinal
apo A-IV synthesis is markedly stimulated by fat absorption and does not appear to be mediated by the uptake or reesterification of
fatty acids to form
triglycerides. Rather, the local 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 (PYY). The inhibition of food intake by
apo A-IV is mediated centrally. The stimulation of intestinal synthesis and 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, as it is regulated by both
leptin and
insulin. Chronic ingestion of a high-fat diet blunts the intestinal as well as the hypothalamic
apo A-IV response to
lipid feeding. It also suppresses
apo A-IV gene expression in the hypothalamus. Whereas it is tempting to speculate that
apo A-IV may play a role in diet-induced
obesity, we believe the confirmation of such a proposal awaits further experimental evidence.