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Acta Physiologica 2012; Volume 206, Supplement 693
Joint FEPS and Spanish Physiological Society Scientific Congress 2012
9/8/2012-9/11/2012
Santiago de Compostela, Spain
ELAIDYL-SULFAMIDE, AN OLEOYLETHANOLAMIDE-MODELED ANTIOBESITY DRUG, REDUCES BODY WEIGHT GAIN AND PLASMA CHOLESTEROL IN RATS
Abstract number: P264
M Decara1 J, Romero-Cuevas2 M, Rivera2 P, Macias-Gonzalez3 M, Vida4 M, J Pavon4 F, Serrano4 A, Cano5 C, Fresno5 N, Perez-Fernandez5 R, Rodriguez de Fonseca4 F, Suarez4 J
1--, Vivia Biotech S.L., Avda. Carlos Haya 75, 1ordm;C, 29010, Mlaga, Spain. ,
2Laboratorio de Medicina Regenerativa, IBIMA/Hospital Carlos Haya, Avda. Carlos Haya 82, 29010, Mlaga, Spain. ,
3de Endocrinologa y Nutricin, IBIMA, Hospital Virgen de la Victoria, Campus Universitario de Teatinos, s/n, 29010, Mlaga, Spain.,
4Laboratorio de Medicina Regenerativa. IBIMA, Hospital Carlos Haya, Avda. Carlos Haya 82, 29010, Mlaga, Spain. ,
5--, Instituto de Qumica Mdica, IQM-CSIC, Juan de la Cierva 3, 28006, Madrid, Spain
Objectives:
We have modeled elaidyl-sulfamide (ES), a sulfamoyl analog of oleoylethanolamide (OEA), a lipid mediator of satiety that works through the peroxisome proliferator activated receptor alpha (PPARa).
Materials:
We have characterized the pharmacological profile of ES (0.3-3 mg/kg) by means of in silico molecular docking to the PPARa?receptor, in vitro transcription through PPARa??and in vitro and in vivo administration to obese rats.
Results:
ES interacts with PPARa binding site in a similar way than OEA, is capable of activating PPARa?and?reduces feeding when administered to food-deprived rats in a dose-dependent manner. When ES was given to obese male rats for 7 days, it reduced feeding and weight gain, lowered plasma cholesterol and reduced plasmatic activity of transaminases, indicating a clear improvement of hepatic function. This pharmacological profile is associated to modulation of both cholesterol and lipid metabolism regulatory genes including the sterol-response-element-binding proteins SREBF1/2 and its regulatory proteins INSIG1/2 in liver and white adipose tissue. ES treatment induced the expression of thermogenenic regulatory genes including the uncoupling proteins UCP1/2/3 in brown adipose tissue and UCP3 in white adipose tissue.
Conclusions:
We propose that ES and related compounds may be useful for the treatment of obesity associated to dyslipemia.
This work is supported by the seventh Framework Programme of European Union (grant number HEALTH-F2-2008-223713, REPROBESITY).
To cite this abstract, please use the following information:
Acta Physiologica 2012; Volume 206, Supplement 693 :P264