Increased apolipoprotein A-IV in rat mesenteric lymph after lipid meal acts as a physiological signal for satiation

Chylomicron transport and apolipoprotein A-IV (apo A-IV) output in mesenteric lymph increases significantly after a lipid meal. Mesenteric lymph collected from lymph-fistula rats after lipid infusion exerted an anorectic effect on 24 h fasted rats after administration through chronically indwelling right atrial catheter. Lymph before lipid infusion and lymph collected from a rat fed lipid plus Pluronic L-81 (a potent inhibitor of chylomicron formation) had no anorectic effect. Chylomicron and apo A-IV-rich lymph lost its anorectic effect after specific immunoprecipitation of apo A-IV by a monospecific antibody. Intravenous infusion of the same amount of purified apo A-IV as in chylous lymph 6-8 h after a lipid meal suppressed food intake. This unique physiological function of apo A-IV is not shared by apolipoprotein A-I. It is proposed that apo A-IV is a circulating signal released in response to fat feeding and that it is likely to mediate the anorectic effect of a lipid meal.