Adipogenesis, diabetes and wnt signalling
The concept of adipose tissue plasticity is well known, as is the fact that a positive energy balance drives increased adiposity in vivo. Less well accepted or indeed understood, are the molecular mechanisms that negatively regulate adipose tissue plasticity particularly under physiological and/or patho-physiological conditions. The latter is clearly relevant when one considers the possibility that there may be a limit in the extent to which adipose tissue can expand. Our laboratory has been investigating two candidate signalling networks that are likely to be important negative local regulators of adipogenesis, In vivo. The Wnt/β-catenin signaling network is implicated in lineage determination of mesenchymal stem cells but is also a good candidate for adipose tissue remodeling during normal physiology. In contrast, pro-inflammatory cytokines such as TNF-α are also potent anti-adipogenic signals and are good candidates for limiting adipose tissue expansion during pathological disease states such as cachexia and obesity-associated metabolic syndrome. Significant strides are now being made in elucidating the regulation, physiological relevance, and molecular effectors of these anti-adipogenic signals. One of our recent studies have identified the Wnt modulator Dapper1 as a new preadipocyte gene involved in the regulation of murine and human adipogenesis. Our findings from this and related studies will be presented. These new insights provide functional networks with therapeutic potential for treating diseases such as obesity and associated metabolic disorders.