Visit our Expo - Redox and Inflammation signaling 2012

Session XIV : Transcriptional and translational control Poster XIV, 17
Lipid metabolism alterations induced by mitochondrial dysfunction in preadipocytes: a
new role for the transcription factor CREB
Aurélia De Pauw 1 , Sebastien Vankoningsloo 1 , Andrée Houbion 1 , Silvia Tejerina 1 ,
Catherine Demazy 1 , Françoise de Longueville 2 , Vincent Bertholet 2 , Patricia Renard 1 ,
José Remacle 1,2 , Martine Raes 1 and Thierry Arnould 1
1
Laboratory of Biochemistry and Cellular Biology, University of Namur (F.U.N.D.P.),
Rue de Bruxelles, 61, 5000 Namur, Belgium. Email : HYPERLINK
"mailto:thierry.arnould@fundp.ac.be" thierry.arnould@fundp.ac.be,
2
Eppendorf
Array Technologies, Rue du Séminaire, 12, 5000 Namur, Belgium.
The role of mitochondria in cellular lipid homeostasis, adipogenesis and insulin sensitivity is
now evidenced in various pathologies resulting from genetic alterations or chronical exposure
to molecules that impair mitochondrial activity. However, the molecular mechanisms
underlying abnormal fat distribution induced by mitochondrial dysfunction remain poorly
understood. In this study, we showed that respiratory complex III inhibition by antimycin A
as well as mitochondrial protein synthesis inhibition trigger the accumulation of triglyceride
vesicles in 3T3-L1 fibroblasts. We also found that antimycin A treatment triggers CREB
activation in these cells. To delineate how mitochondrial dysfunction induces triglyceride
accumulation in preadipocytes, we developed a low-density DNA microarray that contains 89
probes allowing gene expression analysis for major effectors and/or markers of adipogenesis.
We thus determined gene expression profiles in 3T3-L1 incubated with antimycin A and
compared the patterns obtained with differentially expressed genes during the course of in
vitro adipogenesis induced by a standard proadipogenic cocktail. After a 8-day treatment, a
set of 39 genes was found to be differentially expressed in antimycin A-treated cells among
which CHOP-10 (C/EBP homologous protein-10), GPDmit (mitochondrial glycerol-
3phosphate dehydrogenase), and SCD1 (stearoyl-CoA desaturase 1). We also demonstrated
that the overexpression of dominant negative mutants of CREB (K-CREB and M1-CREB) as
well as siRNA transfection that respectively disrupt the factor activity and expression inhibit
antimycin A-induced triglyceride accumulation. These results highlight a new role for CREB
in the control of triglyceride metabolism during the adaptative response of preadipocytes to
mitochondrial dysfunction.
T. Arnould and A. De Pauw are respectively Research Associate and Research Assistant of
FNRS (Fonds National de la Recherche Scientifique, Brussels, Belgium).S. Tejerina is a
recipient of a CUD (Coopération Universitaire au Développement) fellowship.
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