Soy and the soy isoflavone genistein promote adipose tissue development in male mice on a low fat diet

Purpose Several nutrients act as phytoestrogens, being anti-adipogenic when consumed with a fat-rich diet. Their effect on a low-fat diet (LFD) background is unknown. We tested soy and genistein effects on adipose tissue in LFDfed mice and genistein activity in the 3T3-L1 adipogenesis model. Methods C57BL/6 J male mice were fed an 8.5 % soysupplemented LFD (SS-LFD) or a soy-free LFD (SF-LFD) for 147 days. Groups of 3-week-old (pubertal) and 6-weekold (adult) mice on the SF-LFD were also treated with 17ßestradiol (E2, 5 lg/kg/day) ip or pure genistein (5 mg/kg/ day) by gavage for 15 days. Body fat deposition and gene expression profiles were evaluated. E2 and genistein effects on ERa, ERb and PPARc transcriptional activities were characterized in ERa- or ERb-transfected 3T3L1 cells during differentiation, by the use of reporter plasmids. Results The SS-LFD group increased fat mass compared with the SF-LFD group. Genistein alone increased while E2 decreased fat pads in the 15-day-treated mice. In visceral fat, genistein differentially regulated 13 metabolic pathways compared to E2. PPARc-controlled genes were downregulated by E2, while they were upregulated by genistein. In 3T3-L1 cells, genistein activated ERb-driven transcription, differentiation and lipid accumulation, while inhibited ERa-driven transcription, without effects on lipid accumulation. E2 activated both ERs only in preadipocytes. In differentiated untransfected cells, genistein inhibited PPARc, while activated PPARc in the presence of ERb. Conclusions Soy and genistein at nutritional doses induce fat development in LFD-fed mice and adipogenesis in 3T3- L1 cells, with a mechanism that involves, at least in vitro, ERb and is dependent on cell differentiation stage.