Adipogenesis in Rodent Skin, The Dermal Adipose Layer: What Signals Adipocyte Development in the Lower Dermis?

Abstract

Research into adipogenesis has become increasingly more fundamental as our understanding of diabetes and obesity develops. Adipose tissue (fat) exists in many depots throughout the body. While widely known that there is a subcutaneous adipose depot beneath the skin, more recently a separate dermal adipose layer, within the lower dermis of rodent skin, has been found. However, the developmental origins and timings of adipogenesis in this dermal layer are not well characterised. This thesis aims to study adipogenesis within this layer, by creating an in vivo-like model and investigating signalling pathway effects.
Firstly, the hypothesis of an inhibition signal from the upper dermis and the role of the G0/G1 switch gene 2 (G0S2) in the dermal adipose tissue was explored. Experiments showed G0S2 expression in the lower dermis during development. PPARγ has been shown as a main regulator of adipogenesis, together with C/EBPα. The potential role of PPARγ in early adipogenesis was investigated, using immunofluorescence analysis.
Microarray analysis studies previously showed molecular differences between in vitro and in vivo, therefore model systems, more closely related to in vivo conditions, are necessary. An organ culture and a cell culture model were developed. The cell culture model, using 3D cell spheres, proved most useful to investigate signalling in adipocyte development. The EGF/EGFR, TGFβ/BMP and KGF/KGFR pathways were studied, by supplementing cultures with an activator or inhibitor of the receptor of each pathway. Differential levels of oil red O staining and therefore adipocyte formation, were observed.
In conclusion, this work was found to suggest commitment of the cells to the adipocyte lineage begins earlier, than from when microarray data was collected. While not conclusive, it provides an insight and direction for further studies, in terms of PPARγ and potential adipogenic inhibition signals in the upper dermis, as well as a model system.