Abstract
Lipoprotein delivery of fatty acids and cholesterol is linked with peroxisome proliferator-activated receptor (PPAR) activation in adipocytes and macrophages. We postulated that similar interactions exist in sebaceous epithelial cells (sebocytes) in which PPAR activation induces differentiation. High-density lipoprotein (HDL) and very low-density lipoprotein (VLDL) markedly enhanced sebocyte differentiation above that found with PPAR agonists and were more potent than explicable by their lipid content. The PPARγ antagonist GW5393 reduced sebocyte differentiation to all PPAR isoform agonists, HDL and VLDL, suggesting that the lipoprotein effect on differentiation occurs partially through activation of PPARγ. Furthermore, we found that sebocytes expressed a unique pattern of lipogenic genes. Our results demonstrate that HDL and VLDL are the most potent inducers of sebocyte differentiation tested to date, and these actions are partially inhibited by PPAR antagonists. This suggests that substrates provided by lipoproteins are targeted to sebocytes and affect their own disposition via PPAR activation.
Highlights
Sebaceous epithelial cell differentiation is defined by increasing accumulation of lipid droplets, the major component of sebum
We show that the specific PPARδ agonist (GW742) exhibits a dose-response effect on sebocyte differentiation (P < 0.001; Figure 1) and is equipotent to the PPARδ, α agonist cPGI2 at 1 μM
Our studies show that the lipoproteins High-density lipoprotein (HDL) and very low-density lipoprotein (VLDL) are the most effective inducers yet reported of rat sebocyte colony differentiation
Summary
Sebaceous epithelial cell (sebocyte) differentiation is defined by increasing accumulation of lipid droplets, the major component of sebum. Peroxisome proliferator-activated receptor (PPAR) isoforms, which were originally discovered because of their key roles in adipogenesis and lipid metabolism, have been shown to strongly stimulate sebocyte differentiation in vitro [1,2,3,4]. Linoleic acid is the most effective stimulator of sebocyte differentiation tested far [1, 2], but its physiological relevance is suspect since its action requires a relatively high concentration (10−4 M), and it inappropriately stimulates LFCs in epidermal cells [1], which raises the possibility that it mainly acts as a fatty acid substrate for lipogenesis
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