title: Ascorbic acid is a dose-dependent inhibitor of adipocyte differentiation, probably by reducing cAMP pool.
abstract: Ascorbic acid (AA) is the active component of vitamin C and antioxidant activity was long considered to be the primary molecular mechanism underlying the physiological actions of AA. We recently demonstrated that AA is a competitive inhibitor of adenylate cyclase, acting as a global regulator of intracellular cyclic adenosine monophosphate (cAMP) levels. Our study, therefore, aimed to determine new targets of AA that would account for its potential effect on signal transduction, particularly during cell differentiation. We demonstrated that AA is an inhibitor of pre-adipocyte cell line differentiation, with a dose-dependent effect. Additionally, we describe the impact of AA on the expression of genes involved in adipogenesis and/or the adipocyte phenotype. Moreover, our data suggest that treatment with AA partially reverses lipid accumulation in mature adipocytes. These properties likely reflect the function of AA as a global regulator of the cAMP pool, since an analog of AA without any antioxidant properties elicited the same effect. Additionally, we demonstrated that AA inhibits adipogenesis in OP9 mesenchymal cell line and drives the differentiation of this line toward osteogenesis. Finally, our data suggest that the intracellular transporter SVCT2 is involved in these processes and may act as a receptor for AA.
authors.affiliation: Nutrition, Obesity and Risk of Thrombosis, INSERM U 1062, INRA 1260, Aix-Marseille University Marseille, France.
authors.forename: Fryad
authors.initials: F
authors.lastname: Rahman
authors.affiliation: Nutrition, Obesity and Risk of Thrombosis, INSERM U 1062, INRA 1260, Aix-Marseille University Marseille, France.
authors.forename: Fadi
authors.initials: F
authors.lastname: Al Frouh
authors.affiliation: Nutrition, Obesity and Risk of Thrombosis, INSERM U 1062, INRA 1260, Aix-Marseille University Marseille, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Bordignon
authors.affiliation: Service of Electron Microscope, Faculté de Médecine, Aix-Marseille University Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Fraterno
authors.affiliation: Nutrition, Obesity and Risk of Thrombosis, INSERM U 1062, INRA 1260, Aix-Marseille University Marseille, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Landrier
authors.affiliation: Nutrition, Obesity and Risk of Thrombosis, INSERM U 1062, INRA 1260, Aix-Marseille University Marseille, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Peiretti
authors.affiliation: Nutrition, Obesity and Risk of Thrombosis, INSERM U 1062, INRA 1260, Aix-Marseille University Marseille, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Fontes
keywords: adipocytes; ascorbic acid; cell differentiation; cyclic AMP