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Titolo:
A spermine-coupled cholesterol metabolite from the shark with potent appetite suppressant and antidiabetic properties
Autore:
Zasloff, M; Williams, JI; Chen, Q; Anderson, M; Maeder, T; Holroyd, K; Jones, S; Kinney, W; Cheshire, K; McLane, M;
Indirizzi:
Magainin Pharmaceut, Plymouth Meeting, PA 19462 USA Magainin Pharmaceut Plymouth Meeting PA USA 19462 h Meeting, PA 19462 USA
Titolo Testata:
INTERNATIONAL JOURNAL OF OBESITY
fascicolo: 5, volume: 25, anno: 2001,
pagine: 689 - 697
SICI:
0307-0565(200105)25:5<689:ASCMFT>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
OBESE GENE; SQUALAMINE; LEPTIN;
Keywords:
diabetes; obesity; leptin; anorexia; Squalus acanthias; squalamine;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
16
Recensione:
Indirizzi per estratti:
Indirizzo: Zasloff, M Magainin Pharmaceut, S110 Campus Dr, Plymouth Meeting, PA 19462USA Magainin Pharmaceut S110 Campus Dr Plymouth Meeting PA USA 19462
Citazione:
M. Zasloff et al., "A spermine-coupled cholesterol metabolite from the shark with potent appetite suppressant and antidiabetic properties", INT J OBES, 25(5), 2001, pp. 689-697

Abstract

OBJECTIVE: We describe the pharmacological properties of a novel spermine-cholesterol adduct, MSI 1436 (3 beta -N-1(spermine)-7 alpha, 24R-dihydroxy-5 alpha -cholestane 24-sulfate), which causes reversible suppression of food and fluid intake in mammals resulting in profound weight loss, not associated with other signs or symptoms of illness, and which exhibits antidiabetic properties in genetically obese mice. METHODS: Wild-type rodents and strains with genetic obesity were studied. Effects on food and fluid intake, body weight and composition were examinedalong with pharmacological and toxicological parameters. RESULTS: MSI-1436 induces profound inhibition of food and fluid intake in rats and mice, resulting in significant weight loss. MSI-1436 is active when introduced directly into the third ventricle of the rat, suggesting the compound acts on central targets. Pair-feeding studies suggest that MSI-1436causes weight loss by suppressing food intake. Fluid intake is also profoundly reduced but animals remain normally hydrated and defend both water andelectrolyte balance from parenteral administration. MSI-1436 is active in ob/ob, db/db, agouti and MC4 receptor knockout mice. MSI-1436 has been administered to ob/ob mice over a 4 month period via a regimen that safely controls body weight, glucose homeostasis and serum cholesterol levels. Following MSI-1436 treatment, db/db mice preferentially mobilize adipose tissue and hyperglycemia is corrected. CONCLUSION: A naturally occurring spermine metabolite of cholesterol, isolated from the dogfish shark, Squalus acanthias, has been identified that induces profound reduction in food and fluid intake in rodents in a setting where thirst is preserved and fluid and electrolyte homeostasis appears to be functioning normally. MSI-1436 probably acts on a central target involving neural circuits that lie downstream from the leptin and the MC4 receptors. Although long-term administration can be accomplished safely in mice, theutility of this compound as a potential human therapeutic awaits an analysis of its pharmacological properties in man.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 19:10:35