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A Novel Inhibitory Protein in Adipose Tissue, the Aldo-Keto Reductase AKR1B7: Its Role in Adipogenesis

Institut National de la Santé et de la Recherche Médicale, Unité 449; Institut National de la Recherche Agronomique, Unité Mixte de Recherche 1235; and Université Claude Bernard (J.T., J.G., M.B., D.N.), F-69000 Lyon, France; and Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6547 (A.M.L.-M., A.M.), F-63170 Aubière, France

Address all correspondence and requests for reprints to: Danielle Naville, Institut National de la Santé et de la Recherche Médicale Unité 449-Institut National de la Recherche Agronomique Unité Mixte de Recherche 1235, Faculté de Médecine Laennec, 8, rue Guillaume Paradin, 69372 Lyon Cedex 08, France. E-mail: naville{at}lyon.inserm.fr.

The aldo-keto reductase 1B7 (AKR1B7) encodes an aldose-reductase that has been reported as a detoxification enzyme until now. We have demonstrated that AKR1B7 is differently expressed in various mouse white adipose tissues depending on their location. Its expression is associated with a higher ratio of preadipocytes vs. adipocytes. The cells that express AKR1B7 did not contain lipid droplets, and the expression level of akr1b7 was very low in mature adipocytes. We have defined the role of AKR1B7 in adipogenesis using either primary cultures of adipose stromal cells (containing adipocyte precursors) or the 3T3-L1 cell line. Under the same differentiation conditions, adipose stromal cells from tissues that expressed AKR1B7 had a decreased capacity to accumulate lipids compared with those that did not express it. Moreover, the overexpression of sense or antisense AKR1B7 in 3T3-L1 preadipocytes inhibited or accelerated, respectively, their rate of differentiation into adipocytes. In vivo experiments demonstrated that AKR1B7-encoding mRNA expression decreased in adipose tissues from mice where obesity was induced by a high-fat diet. All these results attributed for the first time a novel role to AKR1B7, which is the inhibition of adipogenesis in some adipose tissues.

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