Rat preputial sebocyte differentiation involves peroxisome proliferator-activated receptors

The hallmark of sebaceous epithelial cell (sebocyte) differentiation is the accumulation of fused neutral fat droplets. Very little sebocyte differentiation occurs, however, in primary or organ culture, even upon incubating with androgens, which are required for maturation in vivo. We hypothesized that sebocyte cell culture systems lack activators of the peroxisome proliferator-activated receptors that are involved in adipocyte differentiation, We here report that activation of peroxisome proliferator-activated receptor gamma and alpha by their respective specific Ligands, a thiazolidinedione and a fibrate, induced lipid droplet formation in sebocytes but not epidermal cells, Linoleic acid and carbaprostacyclin, both peroxisome proliferator-activated receptor delta and alpha ligand-activators, were more effective but less specific, stimulating lipid formation in both types of cells. Either was more effective than the combination of peroxisome proliferator-activated receptor gamma and alpha activation, suggesting that peroxisome proliferator-activated receptor delta is involved in this lipid formation. Linoleic acid 0.1 mM stimulated significantly more advanced sebocyte maturation than any other treatment, including carbaprostacyclin, which suggests a distinct role of long chain fatty acids in sebocyte differentiation. Peroxisome proliferator-activated receptor gamma 1 mRNA was demonstrated in sebocytes, but not in epidermal cells; it was more strongly expressed in freshly dispersed than in cultured sebocytes. In contrast, peroxisome proliferator-activated receptor delta mRNA was expressed to a similarly high extent before and after culture in both sebocytes and epidermal cells. These findings are compatible with the concepts that peroxisome proliferator-activated receptor gamma 1 gene expression plays a unique role in the differentiation of sebocytes, while peroxisome proliferator-activated receptor delta activation and long chain fatty acids finalize sebocyte maturation and are capable of stimulating epidermal lipid formation. These findings have implications for the development of new modalities of treatment for acne vulgaris.