EFFECTS OF COMPONENTS DERIVED FROM HPLC PURIFICATION OF HUMAN SATIETIN ON INGESTION, BODY-WEIGHT, AND TASTE-AVERSION IN THE RAT

The putative satiety agent human satietin (h-SAT) once thought to be h omogenous has been separated by high-performance liquid chromatography (HPLC) into components designated peak A (P-A, 53%/w) and Peak B (P-B , 47%/w); P-B contains a putative satiety agent. In Experiment 1, male Sprague-Dawley rats were divided into six (n = 9-11) groups (Grps) an d ICV infused: Grp 1, artificial cerebrospinal fluid (a-CSF), 10 mu l/ rat; Grp 2, albumin (ALB), 53 mu g/rat; Grp 3, semipurified (sp) h-SAT (parent compound), 100 mu g/rat; Grp 4, P-A, 53 mu g/rat; Grp 5, P-B, 47 mu g/rat; and Grp 6, P-A+B, 53 + 47 mu g/rat, respectively. Compar ed to Grp 1, food intake, the first day postinfusion, was suppressed i n Grp 3 (p < 0.01) and equally attenuated (p < 0.06) in Grps 5 and 6. Body weight remained suppressed (p < 0.05) in Grps 3, 5, and 6 for 3 d ays and in Grps 3 and 6 (p < 0.05) for an additional 3 days; Grps 2 an d 4 did not differ from Grp 1. These data show P-B suppresses food int ake comparably to P-A+B and causes a prolonged weight loss. In Experim ent 2, sph-SAT and a recombination of P-A and P-B was tested for avers iveness using the two-bottle test. Both sph-SAT and P-A + B significan tly suppressed food intake, but only sph-SAT was found to be aversive. These data show that most likely during HPLC processing of sph-SAT an aversive component was lost.