Growth restriction in utero is associated with increased risk of obesity in later life. Recently, epigenetic inheritance was identified as an important component of this phenomenon, but the precise molecular mechanisms that underpin the association between growth restriction and obesity remain unknown. Now, on p. , Walter Stünkel and colleagues report a role for SOX6 in adipocyte differentiation, and suggest that SOX6 may be a key player in the association between growth restriction and obesity. By comparing adipocytes differentiated from mesenchymal stem cells from normal and growth-restricted newborn umbilical cords, the authors show that SOX6 is upregulated in growth-restricted adipocytes and that it activates key adipogenic players including PPARγ, C/EBPα and MEST. The authors also show that SOX6 interacts with β-catenin, possibly inhibiting WNT/β-catenin signalling to promote adipogenesis. Importantly, the role of SOX6 in regulating adipogenesis was also demonstrated in vivo, using Sox6 antisense oligonucleotides to target white adipose tissue in mice. Taken together, these data demonstrate a clear role for SOX6 in regulating adipocyte differentiation and adipogenesis in vivo, and provide a possible mechanistic link between growth restriction in utero and obesity in later life.
