Disruption of the behavioral satiety sequence by simmondsin.

Simmondsin, a cyanoglycoside from jojoba meal, reduces food intake after oral administration. To diagnose if it acts by inducing satiation or by creating abnormal physiological effects, an observational study was undertaken to investigate the effects of simmondsin on feeding and other behaviors. Particular attention was paid to the behavioral sequence associated with satiety (BSS). At first contact, simmondsin non-significantly reduced food intake by 17% and had little effect on feeding and associated behaviors. The behavioral structure was preserved and a small shift of the onset of resting to the left was observed, suggesting a small satiative action of simmondsin at first contact. Simmondsin given for the second time caused a more pronounced food intake reduction of 52% due to a reduction in eating duration, mean bout intake and mean bout length, and to an increase in latency to eat. At second contact, simmondsin caused a strong switching in active behaviors, disrupting the BSS. The simmondsin-induced hyperactivity suggests that simmondsin produces aversiveness with second contact. Our results indicate that simmondsin exerts multiple effects. It probably facilitates a small natural process of satiation/satiety at first contact, but creates abnormal physiological effects resulting in aversive reactions from second contact on.

Receptor-mediated biological responses are prolonged using hydrophobized ligands.

Hormone-receptor interactions occur following three-dimensional diffusion of the ligand to the membrane-embedded receptor. However, prior hydrophobization of the ligand might restrict its movement to two dimensions along the membrane surface, and the biological response might therefore be modulated. This idea was tested using the C-terminal nonapeptide, CCK9, of the satiating hormone, cholecystokinin (CCK). The hormone was lipidated by linking it covalently to distearoylphosphatidylethanolamine via a poly(ethylene glycol) (PEG) spacer. The desired conjugate was isolated by thin-layer chromatography and incorporated into preformed small unilamellar dimyristoylphosphatidylcholine (DMPC) vesicles. The hormone-bearing vesicles were injected intraperitoneally into Wistar rats and food intake monitored. Compared to the biological effect elicited by the same amount of soluble non-derivatized CCK9, food intake reduction showed a delayed onset, but lasted for a significantly longer time. We believe this prolonged effect was due to the transfer of the derivatized CCK9 from the vesicles to the natural membrane containing the hormone receptor. Ultimately, this event may result in sustained receptor occupation and, thus, food intake reduction. The underlying mechanism for the physiological effects observed may be of relevance in interpreting results obtained using artificial measuring devices; for example, the signal produced by biosensors may be drastically affected by the hydrophobicity of the ligand.

Simmondsin: effects on meal patterns and choice behavior in rats.

Simmondsin, a glycoside from jojoba meal, decreases food intake after oral administration. The present experiments are designed to clarify the mechanism of simmondsin's anorectic activity. The meal pattern analysis shows that simmondsin supplementation at different doses results in a dose-dependent food intake reduction, which is more pronounced after prior simmondsin experience. The effect of simmondsin on meal patterns (decreased meal size, meal duration and eating rate, increased latency to eat) is most severe at the highest concentration. Rats familiar with simmondsin more seriously postpone their first meal than with first contact, resulting in a decrease of the meal frequency and the day/night feeding ratio. Rats given the choice between a control diet and a simmondsin-supplemented (0.5%) diet, after half an hour, have a significant preference for the control diet. Simmondsin seems to have a specific flavor when mixed in the food since rats recognise the feeder containing simmondsin. The ability of simmondsin to induce conditioned taste aversion (CTA) was also investigated. Rats receiving simmondsin at concentrations of 0.15%, 0.25% or 0.5% during their conditioning develop significant taste aversions to the saccharin solutions. The performed experiments indicate that the simmondsin activity shows some analogy with the satiating molecule cholecystokinin (CCK) at first contact, but shows more analogy with the illness-inducing agent lithium chloride (LiCl) after prior experience with simmondsin. Rats familiar with simmondsin avoid simmondsin-supplemented food by directly monitoring its presence, and by learning to relate it to the postingestive consequences of consumption.

Simultaneous determination of carbohydrates and simmondsins in jojoba seed meal (Simmondsia chinensis) by gas chromatography.

Separate methods for the analyses of soluble carbohydrates in different plants and simmondsins in jojoba seed meal are described. A reliable gas chromatographic procedure for the simultaneous quantification of D-pinitol, myo-inositoL sucrose, 5-alpha-D-galactopyranosyl-D-pinitol. 2-alpha-D-galactopyranosyl-D-pinitol, simmondsin, 4-demethylsimmondsin, 5-demethylsimmondsin and 4,5-didemethylsimmondsin as trimethylsilyl derivatives in jojoba seed meal has been developed. The study of different extraction mixtures allowed for the quantitative recovery of the 9 analytes by a mixture of methanol-water (80:20, v/v) in the concentration range between 0.1 and 4%. Comparison of the separation parameters on three different capillary stationary phases with MS detection allowed for the choice of the optimal gas chromatographic conditions for baseline separation of the analytes.