Aldose Reductases Influence Prostaglandin F<sub>2α</sub> Levels and Adipocyte Differentiation in Male Mouse and Human Species - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Endocrinology Année : 2015

Aldose Reductases Influence Prostaglandin F Levels and Adipocyte Differentiation in Male Mouse and Human Species

Résumé

Aldose reductases (AKR1B) are widely expressed oxidoreductases whose physiological function remains elusive. Some isoforms are genuine prostaglandin F2α (PGF2α) synthases, suggesting they might influence adipose homeostasis because PGF2α inhibits adipogenesis. This was shown by Akr1b7 gene ablation in the mouse, which resulted in increased adiposity related to a lower PGF2α content in fat. Yet humans have no ortholog gene for Akr1b7, so the role of aldose reductases in human adipose homeostasis remains to be explored. We analyzed expression of genes encoding human and mouse aldose reductase isoforms in adipose tissues and differentiating adipocytes to assess conserved mechanisms regulating PGF2α synthesis and adipogenesis. The Akr1b3 gene encoded the most abundant isoform in mouse adipose tissue, whereas Akr1b7 encoded the only isoform enriched in the stromal vascular fraction. Most mouse aldose reductase gene expression peaked in early adipogenesis of 3T3-L1 cells and diminished with differentiation. In contrast with its mouse ortholog Akr1b3, AKR1B1 expression increased throughout differentiation of human multipotent adipose-derived stem cells, paralleling PGF2α release, whereas PGF2α receptor (FP) levels collapsed in early differentiation. Pharmacological inhibition of aldose reductase using Statil altered PGF2α production and enhanced human multipotent adipose-derived stem adipocyte differentiation. As expected, the adipogenic effects of Statil were counteracted by an FP agonist (cloprostenol). Thus, in both species aldose reductase-dependent PGF2α production could be important in early differentiation to restrict adipogenesis. PGF2α antiadipogenic signaling could then be toned down through the FP receptor or aldose reductases down-regulation in human and mouse cells, respectively. Our data suggest that aldose reductase inhibitors could have obesogenic potential.
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hal-02108053 , version 1 (22-10-2019)

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Emilie Pastel, Jean-Christophe Pointud, Gaëlle Loubeau, Christian Dani, Karem Slim, et al.. Aldose Reductases Influence Prostaglandin F Levels and Adipocyte Differentiation in Male Mouse and Human Species. Endocrinology, 2015, 156 (5), pp.1671-1684. ⟨10.1210/en.2014-1750⟩. ⟨hal-02108053⟩
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