Apolipoprotein A-IV: a circulating satiety signal produced by the small intestine

How fat feeding, especially lipoproteins and apolipoproteins, may affect food intake is unclear. Apolipoprotein A-IV (apo A-IV) is a protein associated with chylomicrons, and its synthesis by the small intestine is markedly stimulated following ingestion of fat. We explored the anorectic effect of chylous lymph on feeding behavior. Intestinal lymph samples collected during lipid infusion intraduodenally when administered intravenously markedly suppressed food intake in fasting rats. To determine if the suppressor was lipid or apo A-IV, fasting rats were infused intravenously with a 2% Intralipid emulsion, but it did not suppress food intake. These data suggest that the factor in chylous lymph that suppresses food intake is probably apo A-IV. To test this, apo A-IV in chylous lymph was removed by immunoprecipitation, and the chylous lymph with apo A-IV removed lost its anorectic effect. Next, we infused purified apo A-IV intravenously in fasted rat, and it inhibited food intake in a dose-dependent manner. We therefore conclude that increased apo A-IV in chylous lymph is a factor involved in anorexia after fat feeding. Infusion of 0.5 microgram of apo A-IV into the third ventricle failed to suppress food intake. Higher doses (1 microgram or higher) of apo A-IV infused into the third ventricle inhibited food intake in a dose-dependent manner. To further test the hypothesis that apo A-IV is an important factor controlling food intake, we administered goat anti-rat apo A-IV serum into the third ventricle of rats that were allowed food and water ad libitum. In all rats tested, this treatment resulted in enhanced food intake. In conclusion, we propose that apo A-IV may act centrally to control food intake.