Satietin; a 50,000 dalton glycoprotein in human serum with potent, long-lasting and selective anorectic activity

Abstract

Satietin, a 50,000 dalton anorectic glycoprotein was isolated from human serum. Its isoelectric point is 7.0. It contains 14-15% amino acids and 70-75% carbohydrates. Its biological activity survives digestion with proteases and boiling. Satietin is a highly potent anorectic substance. The intracerebroventricular administration of 10-20 micrograms satietin suppresses food intake in rats during the first day of feeding after deprivation of food for 96 hours to half of the amount eaten by untreated controls (ID50). The onset of the effect can be detected within 30 minutes, the peak effect is reached within an hour. The effect lasts 24-30 hours. Satietin acts both at intravenous and subcutaneous administration (ID50 = 0.5-0.75 mg/kg) in rats deprived of food for 96 hours. The peak effect is reached within an hour and lasts over 24 hours. In contrast to the anorectic drugs in clinical use and to the endogenous anorectic substances (like cholecystokinin and calcitonin) satietin proved to be highly selective in suppressing food intake. Considering that satietin is widely distributed in the world of vertebrates, its concentration in the blood is amazingly high, its site of effect is in the central nervous system and it induces satiety without having any other detectable central or peripheral effect, the hypothesis was forwarded that satietin may play the role of a rate limiting blood-borne satiety signal in the negative feedback of food intake, i.e. serving as the essential chemical link connecting the gastrointestinal tract and the brain in the regulation of feeding.

Endogenous Anorectic Agents-Satietins

“…Independent of the route of ad ministration, the peak effect was reached within 1 hr, and the inhibition of food intake lasted over 24 hr (74,84,85).…”

“…As the essential mechanism of action of an anorectic compound, i.e. whether it acts via feeding or satiety, can be resolved by analyzing the substance-induced changes in the micro structure of eating, the effect of satietin in comparison to amphetamine and fenfluramine was studied in this respect (74,89).…”

“…With the aid of TCA most of the higher molecular weight proteins and peptides that accompany satietin in the ultrafiltrate could be percipitated. The isolation procedure was then followed by two steps of gelchromatography (using Sephadex G 15 and Bio-Gel P-2 columns), continued with affinity chromatography on Con-A-Sepharose column, and finished by a last desalting step on Bio-Gel P-2 column (68)(69)(70)(71)(72)(73)(74).…”

Satietins, α1‐glycoproteins in human plasma with potent, long‐lasting and selective anorectic activity

“…Up to the present we detected and isolated two closely related anorectic al-glycoproteins from human serum which I named satietin and satietin-D, respectively (for a review see ref. 16).…”

“…16). Nine peptides, the most relevant ones, are listed in Table VII, showing the main physiological effects of these endogenous substances which are exerted in the physiological dose range of the peptides, whereas usually much higher doses are needed (i.v.…”