Effects of Combined Oleoyl-Estrone and Rimonabant on Overweight Rats

• Published in: Journal of Pharmacological Sciences Vol. 104; no. 2; pp. 176 - 182
• Main Authors: Ferrer-Lorente, Raquel, Cabot, Cristina, Fernández-López, José-Antonio, Alemany, Marià
• Format: Journal Article
• Language: English
• Published: Japan Elsevier B.V 2007; The Japanese Pharmacological Society; Elsevier
• Subjects: adipose tissue; Animals; Anti-Obesity Agents - pharmacology; Appetite - drug effects; Blood Glucose - drug effects; Cholecystokinin - blood; Cholecystokinin - drug effects; Cholesterol - blood; Drug Synergism; Drug Therapy, Combination; Eating - drug effects; energy balance; Energy Metabolism - drug effects; Estrone - analogs & derivatives; Estrone - pharmacology; Fatty Acids, Nonesterified - blood; Ghrelin; Glucagon-Like Peptide 1 - drug effects; Glucagon-Like Peptide 1 - metabolism; Insulin - blood; Leptin - blood; Male; obesity; Obesity - drug therapy; Oleic Acids - pharmacology; oleoyl-estrone; Overweight - drug effects; Peptide Hormones - blood; Peptide Hormones - drug effects; Piperidines - pharmacology; Pyrazoles - pharmacology; Rats; Rats, Wistar; Rimonabant; Triglycerides - blood; adipose tissue; oleoyl-estrone; rimonabant; energy balance; obesity
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.FP0061441

Oleoyl-estrone (OE) decreases appetite, maintains energy expediture, induces lipolysis (sparing protein), and decreases cholesterolemia and insulin resistance. Rimonabant (SR141716) is a cannabinoid-receptor inhibitor that decreases appetite and mobilizes fat. We studied whether their combination improves their slimming effects. Male overweight rats Received daily gavages of 5.3 mg/kg OE, 10 mg/kg rimonabant, or both drugs during 10 days. Body weight and composition, energy balance, adipose tissue weight, and serum hormones and metabolites were measured. OE halved food intake and maintained energy expenditure at the expense of body fat. Rimonabant effects on appetite and energy balance were less marked, resulting in lower lipid mobilization. OE and rimonabant followed the OE pattern, with no additive or synergic effects. Glycemia was maintained, but OE decreased insulin, GLP-1, and cholesterol, whilst rimonabant increased cholecystokinin and cholesterol, and decreased NEFA. Both drugs decreased leptin and triacylglycerols; ghrelin was unchanged. The results hint at different mechanisms of action of both drugs: we can assume that OE effects do not involve the cannabinoid pathway. OE does not seem to act, either, after 10 days, through the secretion of ghrelin or the intestinal appetite-controlling peptides tested.