White adipose tissue development is tightly regulated by pro-and anti-adipogenic factors. In obesity, its increased development leads to many metabolic complications. To date, little is known about the factors that control negatively its growth. In this context, the laboratory has focused researches on the murine aldose reductase Akr1b7 role in white adipose tissue. Akr1b7 is expressed in stromal vascular fraction of white adipose tissue and exhibits an anti-adipogenic action on a preadipocyte cell line. Generation and study of Akr1b7-/- knockout mice allows us to demonstrate that lack of Akr1b7 leads to adipose tissue expansion due to hypertrophy and hyperplasia of adipose cells associated to insulin resistance. Akr1b7-/- mice are not hyperphagic but show reduced basal metabolic rate. This phenotype confirms Akr1b7 involvement in adipose tissue physiology. Akr1b7 regulates development of adipose tissue by a PGF2α-dependent inhibition of both adipogenesis and lipogenesis. On the other hand, we have developed a transgenic murine model over-expressing the human aldose reductase AKR1B1 in adipose tissue. Against all odds and contrary to Akr1b7, this model shows a pro-adipogenic effect of AKR1B1. These in vivo data reveal new and opposed activities of different aldose reductase isoforms and open new avenues to understand the mecanisms regulating fat homeostasis and its disturbances.
Role of aldose reductases in the physiology of white adipose tissue : murine genetic models of loss and gain of function