Effects of fat cells on keratinocytes and fibroblasts in a reconstructed rat skin model using collagen gel matrix culture

BACKGROUND: Fat cells (stromal tissue cells), not only have the function of lipid metabolism, but produce various cytokines that exert an influence on other cell types through paracrine or endocrine mechanisms. OBJECTIVES: To elucidate possible roles of fat cells in the skin, we examined their effects on the biological behaviour of keratinocytes and dermal fibroblasts in culture. METHODS: In the present study, focusing upon fat cell--keratinocyte or fat cell--dermal fibroblast interactions, we used a reconstructed skin system with rat skin cells in a three-dimensional collagen gel matrix culture. RESULTS: In this coculture system, fat cells promoted the proliferation and differentiation of keratinocytes. When keratinocytes were seeded directly on the fat cell layer without dermal fibroblasts, they proliferated extensively and formed a thick epidermal layer with a well-differentiated structure. Conversely, fat cells inhibited the proliferation of dermal fibroblasts. These effects of fat cells were presumed to be mediated by cytokines derived from the fat cells. CONCLUSIONS: The effects of fat cells could not be mimicked by the addition of leptin, tumour necrosis factor-alpha or insulin-like growth factor-II, suggesting that fat cells are mediating these activities via some other cytokines.