The study of PPAR expression profiles and the identification of target genes and ligands in the skin and its appendages as well as the utilization of PPAR mouse mutant models have unveiled distinct physiological functions of the PPARs (Table 3). In particular, activation of PPARs regulates differentiation and proliferation, lipid metabolism, inflammation, and apoptosis. However, the molecular mechanisms by which PPARs coordinate the regulation of these processes remain largely unknown, and thus PPARs represent a major research target for the understanding and treatment of many skin diseases including acne.
The research reviewed here focused on PPAR activity in human epidermis and its appendages. The data demonstrates that PPARs regulate many of the physiological processes that are involved in acne. However, it is also apparent that there is some discrepancies with regard to the physiological effects of PPAR ligands on sebaceous lipogenesis, which may be attributed to the different study models used, but this requires further elucidation. It would be of particular interest to evaluate the efficacy of PPAR ligands on acne and other skin disorders in the clinic.
Since the completion of this manuscript, more research has been done into examining the effects of PPAR ligands on sebaceous lipogenesis. The PPAR ligands GW7647, GW0742, GW2433, rosiglitazone, and GW4148 significantly increased lipogenesis in SEB-1 sebocytes (121), confirming earlier reports referenced in this chapter. Interestingly, patient data collected in the same paper showed increased sebum secretion in patients receiving fibrates for hyperlipidemia or thialzolidienediones for diabetes. However, this is in contrast to observation in healthy volunteers, and one might argue that these patients are treated for metabolic diseases of the liver and pancreas, which may also effect sebaceous gland metabolism, and therefore these data should be treated with caution. In addition, PPAR involvement in the prostaglandin pathway has been shown in a recent paper where PPARy activation has been implicated in oxidative stress-mediated prostaglandin E(2) production in SX95 human sebaceous cells (122).
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