Apolipoprotein A-IV (
apo A-IV) is secreted by the intestine associated with
chylomicron. Intestinal
apo A-IV synthesis is stimulated by fat absorption, which is probably mediated by
chylomicron formation. The stimulation of
apo A-IV synthesis in the jejunum and ileum is attenuated by intravenous
leptin infusion. Intestinal
apo A-IV synthesis is also stimulated by
a factor from the ileum, probably
peptide tyrosine-tyrosine (PYY), which has been demonstrated to affect satiety.
Apo A-IV has been proposed to physiologically control food intake, a function not shared by
apo A-I, and this inhibitory effect is centrally mediated. Recently,
apo A-IV was demonstrated in the hypothalamus. The hypothalamic
apo A-IV level was reduced by food deprivation and restored by
lipid feeding. Intracerebroventricular administration of
apo A-IV antiserum increased feeding and decreased the hypothalamic
apo A-IV mRNA level, implying that feeding is normally limited by endogenous
apo A-IV. Central administration of
neuropeptide Y (NPY) significantly increased hypothalamic
apo A-IV mRNA levels in a dose-dependent manner. The stimulation of intestinal synthesis and secretion of
apo A-IV by
lipid absorption are rapid; thus,
apo A-IV is capable of short-term regulation of food intake. Evidence also suggests
apo A-IV's involvement in the long-term regulation of food intake and
body weight. Chronic ingestion of high fat blunts the hypothalamic
apo A-IV response to
lipid feeding and may therefore explain why chronic intake of high fat predisposes animals and humans to
obesity.