Antiadipogenic effect of carnosic acid, a natural compound present in Rosmarinus officinalis, is exerted through the C/EBPs and PPARγ pathways at the onset of the differentiation program

M GAYA; V. REPETTO; J. TONEATTO; C. ANESINI; G. PIWIEN PILIPUK; S. MORENO

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS

ELSEVIER SCIENCE BV

Lugar: Amsterdam ; Año: 2013 vol. 1830 p. 3796 - 3806

0304-4165

Background: Obesity is a serious health problem all over the world, and inhibition of adipogenesis constitutes one of the therapeutic strategies for its treatment. Carnosic acid (CA), the main bioactive compound of Rosmarinus officinalis extract, inhibits 3T3-L1 preadipocytes differentiation. However, very little is known about the molecular mechanism responsible for its antiadipogenic effect. Methods: we evaluated the effect of CA on the differentiation of 3T3-L1 preadipocytes analyzing the process of mitotic clonal expansion, the level of adipogenic markers, and the subcelular distribution of C/EBPâ. Results: CA treatment only during the first day of 3T3-L1 differentiation process was enough to inhibit adipogenesis. This inhibition was accompanied by a blockade of mitotic clonal expansion. CA did not interfere with C/EBPâ and C/EBPä mRNA levels but blocked PPARã, and FABP4 expression. C/EBPâ has different forms known as LIP and LAP. CA induced an increase in the level of LIP within 24 h of differentiation, leading to an increment in LIP/LAP ratio. Importantly, overexpression of LAP restored the capacity of 3T3-L1 preadipocytes to differentiate in the presence of CA. Finally, CA promoted subnuclear de-localization of C/EBPâ. Conclusions: CA exerts its anti-adipogenic effect in a multifactorial manner by interfering mitotic clonal expansion, altering the ratio of the different C/EBPâ forms, inducing the loss of C/EBPâ proper subnuclear distribution, and blocking the expression of C/EBPá and PPARã.