Background and aims-The mechanism of intraduodenal fat induced inhibition of food intake is still unclear. Therefore, we tested the ability of duodenal fatty acids to suppress food intake at a lunchtime meal; in addition, we were interested to test if these eVects were mediated by cholecystokinin (CCK) A receptors. Subjects and methods-Three sequential double blind, three period crossover studies were performed in 12 healthy males each: (1) subjects received intraduodenal fat with or without 120 mg of tetrahydrolipstatin, an inhibitor of gastrointestinal lipases, or saline; (2) volunteers received intraduodenal long chain fatty acids, medium chain fatty acids, or saline; (3) subjects received long chain fatty acids or saline together with concomitant intravenous infusions of saline or loxiglumide, a specific CCK-A receptor antagonist. The eVect of these treatments on food intake and feelings of hunger was quantified. Results-Intraduodenal fat perfusion significantly (p<0.05) reduced calorie intake. Inhibition of fat hydrolysis abolished this eVect. Only long chain fatty acids significantly (p<0.05) decreased calorie intake, whereas medium chain fatty acids were ineVective. Infusion of loxiglumide abolished the eVect of long chain fatty acids. Conclusions-Generation of long chain fatty acids through hydrolysis of fat is a critical step for fat induced inhibition of food intake; the signal is mediated via CCK-A receptors. (Gut 2000;46:688-693)

In healthy subjects, tegaserod markedly accelerated gastric emptying and small intestinal transit, and induced a small but significant acceleration of colonic transit. Tegaserod can act as a promotile agent throughout the gastrointestinal tract.

Exogenous cholecystokinin (CCK) induces early satiety when infused into humans. Whether alimentary CCK (CCK-A) receptor blockade stimulates food intake in humans is, however, uncertain. The aim of the present investigation was, therefore, to establish the effect of CCK-A receptor blockade on satiety and eating behavior in healthy volunteers. To further explore the role of endogenous CCK, the effects of the specific CCK-A receptor antagonist loxiglumide (Lox; 22 micromol. kg(-1). h(-1)) on satiety and eating behavior were investigated in healthy men and compared with saline infusions (as placebo) in a series of randomized, double-blind, placebo-controlled, crossover studies. Lox produced a slight (7%), but not significant (P = 0.104), increase in food intake that was accompanied by a modest (10%), but significant (P < 0.004), increase in calorie intake. Fluid ingestion was not affected by Lox. Subjects experienced more hunger and delayed fullness during Lox infusion than during saline infusion (P < 0.05). This study provides further evidence that CCK is an endogenous physiological satiety signal acting through CCK-A receptor-mediated mechanisms. Repeated-dose studies comparing hunger and satiety responses after CCK-A receptor blockade in healthy subjects and patients with eating disorders may help clarify the possible involvement of endogenous CCK in these conditions.

Intraduodenal fat inhibits gastric emptying and exerts early satiation in animals and humans, but it is not clear whether the effects are mediated by cholecystokinin (CCK) in humans. Here, we tested whether CCK-A receptors mediate the inhibition of fat on food intake. Two sequential, double-blind, crossover studies were performed in 24 male subjects. First, subjects received either intraduodenal fat or saline together with a preload of either water or banana shake. Second, 12 subjects received either intraduodenal fat or saline perfusion plus a concomitant infusion of saline or loxiglumide, a specific CCK-A receptor antagonist, together with a preload of banana shake. In both studies, subjects were free to eat and drink as much as they wished. Fat induced a reduction in calorie intake (P < 0.05) compared with controls. Furthermore, a decrease in hunger feelings was observed. Infusion of loxiglumide abolished the effects of fat. Duodenal fat interacts with an appetizer to modulate energy intake in humans. This effect is mediated by CCK-A receptors.

u. I. Elmadfa, Reduzierung d e r Lipidperoxidation in Forellenfilet durch Supplementierung des Futters mit Vitamin E, Erniihrungsumschau 41, (3) 116 [1994]. H. Schdfer u . I. Elmadfa, Die Wirkung nicht verseifbarer Nahrungsfettkomponenten auf die Lipidperoxidation in Abhlngigkeit des Fettsluremusters, Fette Seifen . Anstrichmittel 85, H. Schdfer u. I. Elmadfa, EinfluB verschiedener Lagerungstemperaturen u n d Lagerungszeiten auf die Peroxidbildung in Fut-563-566 [ 19831. terproben bei Zusatz von a-o d e r y-Tocopherol, Tierphysiol. Tierernahr., Futtermittelkunde 51 (4). 229 -236 [1984]. A. Kornfefd and L. E. Croon, 4-Dimethyl-4-monomethyl and 4,4-dimethylsterols in some vegetable oils, Lipids 16, 306-314 [1981]. B. Schmirr, N . Both u. 1. Elmadfa, Der EinfluB unverseifbarer Nahrungskomponenten auf d a s Plasmacholesterin d e r Ratte bei cholesterinarmer Diat in Abhangigkeit vom FettsPuremuster, Fette . Seifen . Anstrichmittel 85,577-581 [1983].Eingegangen a m 23. Januar 1995.Tocopherole -Antioxidantien der Natur * G . P o n g r a c z , H . W e i s e r u n d D . M a t z i n g e r ** E Hoffmann-La Roche AG, Basel, SchweizDie Tocopherole sind biologisch wirksame Naturstoffe. Sie sind sowohl in vivo als auch in vitro wirksam. Vitamin E ist das wichtigste fettlosliche Antioxidans in den Zellmembranen, aber ebenso auch in den pflanzlichen blen. Die Gemeinsamkeiten resp. Unterschiede in der Wirkung in vivo und in vitro werden bei folgenden Tocopherolen diskutiert:-Tocopherol- Homologe: a-, 8-, y-. &Tocopherol (TL); hachste Vitamin-E-Wirkung a-TL; beste Antioxidans (A0)-Wirkung in vitro y-TL. -Tocotrienole ('IT): Hachste Vitamin-E-Wirkung a-TT (30% von a-TL); beste AO-Wirkung y -n . a-Tocopherol-Stereoisomere: RRR-, RRS-, RSS-, SSS-, RSR-, SRS-, SRR-, SSR-a-TL. AktivitBtsbereich: In abnehmender Reihenfolge von 1.0 bis 0.21; AO-Wirkung in vitro: Alle 8 Stereoisomere sind identisch. AktivitPtsverhBltnis all-rac-: RRR-a-TL-Acetat-. 1:1.36. -Iso-a-Tocopherol (2-Phyty1, 2-methy1, 5,6,7-trimethyl, 8-chromanol): Keine in vivo-Wirkung im Oxydationsmittel induzierten HPmolysetest; linear ansteigende AO-Wirkung in Speisefetten ohne pro-oxidative Wirkung in haheren Konzentrationen.