Apolipoprotein A-IV, food intake, and obesity.
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.
Tso
Patrick
P
Department of Pathology, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA. tsopp@email.uc.edu
Liu
Min
M
D000315:Adrenalectomy / Q000379:methods; D000818:Animals; D001054:Apolipoproteins A / Q000235:genetics / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007421:Intestine, Small / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology; D050356:Lipid Metabolism; D009478:Neuropeptide Y / Q000008:administration & dosage; D009765:Obesity / Q000378:metabolism*; D014628:Vagotomy / Q000379:methods
D001054:Apolipoproteins A; D004151:Dipeptides; D020738:Leptin; D009478:Neuropeptide Y; C042696:tyrosyltyrosine