Visit our Expo - Redox and Inflammation signaling 2012

Session XIV : Transcriptional and translational control Poster XIV, 70
Characterization of 3T3-L1 adipocytes dedifferentiation induced by a mitochondrial
dysfunction
Silvia Tejerina1, Aurélia De Pauw1, Sebastien Vankoningsloo1, Andrée Houbion1,
Catherine Demazy1, Françoise de Longueville2, Vincent Bertholet2, Patricia Renard1,
José Remacle1,2, Martine Raes1 and Thierry Arnould1
1Laboratory of Biochemistry and Cellular Biology, University of Namur (F.U.N.D.P.),
Rue de Bruxelles, 61, 5000 Namur, Belgium. Email : thierry.arnould@fundp.ac.be,
2Eppendorf Array Technologies, Rue du Séminaire, 12, 5000 Namur, Belgium.
Studies of several lipid disorders have evidenced a strong link between mitochondrial
dysfunction and fat storage abnormalities and it is now well accepted that a mitochondrial
dysfunction affects lipid-metabolizing tissues. However, molecular mechanisms involved in
the adipocyte dedifferentiation programme are still poorly understood. In this study, we set up
an experimental model to characterize the dedifferentiation of 3T3-L1 adipocytes induced by
a mitochondrial dysfunction triggered by FCCP, an uncoupling molecule. Differentiating
adipocytes incubated for several days with FCCP show modifications in their phenotype and
are characterized by a decrease in the triglyceride content accompanied by an increase in
glycerol release (a marker of fatty acid mobilization). However, mechanisms and cell
signaling seem to be totally different than the ones triggered by TNFalpha! a cytokine
known to stimulate adipocyte dedifferentiation, as PKA and MEK1/2 inhibitors do not modify
the triglyceride content in FCCP-treated adipocytes. Using a low density cDNA microarray
allowing gene expression analysis for numerous adipogenic markers, we also found a
significant decrease in the expression of genes encoding key transcription factors involved in
adipogenesis (PPARgamma and C/EBPalpha) in adipocytes with impaired mitochondrial
activity. Decrease in the activity of these transcriptional regulators has also been confirmed by
DNA-binding activity assays. Finally, among the genes found to be differentially expressed in
differentiating adipocytes, CHOP-10/GADD153, a natural dominant negative mutant of
C/EBPbeta is specifically up-regulated in adipocytes with uncoupled mitochondria. These
results highlight some new effectors potentially involved in adipocyte dedifferentiation in
response to a 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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