Coding Skin for Care: PPAR Ligands as Retinoid Alternatives and Adjuvants—An Exploration

Jan 6th, 2022

John Simon Craw, Ph.D. Rodan & Fields, San Francisco; George Majewski, Contrast Product Development, Walnut, CA

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Read the full article in the January 2022 digital edition. . .

PPAR refers to “peroxisome proliferator-activated receptors,” which are proteins found in the nucleus of cells. These receptors occur as three different isoforms: PPARα, PPARβ/δ and PPARγ. In skin, PPARs are expressed in cell types including keratinocytes, melanocytes, sebocytes, adipocytes and hair follicles. Similar to other nuclear receptors, such as retinoid and vitamin D receptors, PPARs are ligand-activated transcription factors that alter cellular functions. With ligand-induced activation, PPARs form a complex by heterodimerizing with RXR retinoid receptors, which binds to the PPAR-response element location on the DNA strand, leading to an increase or decrease in expression of the target genes.^{1, 2}

Both natural endogenous and synthetic PPAR ligands are known to produce a range of skin-related bioactivities, including the synthesis of epidermal lipids and proteins, maintenance of epidermal homeostasis and the regulation of energy metabolism on a transcriptional level. For example, the activation of PPARα and PPARγ by linolenic acids has been shown to induce anti-proliferative effects; promote differentiation and stratum corneum formation; increase expression of ceramides, filaggrin, transglutaminase-1, loricrin, involucrin and aquaporin-3; and increase lamellar body formation. Further, all PPAR isotypes exert anti-inflammatory effects through the regulation of major inflammatory markers, e.g., TNFα, IL1, IL-6, IL8, making PPARs a useful target for functional skin care.³

References

Hawkins, S.S., Shingleton, W., Adamus, J. and Meldrum, H. (2010). Peroxisome proliferator-activated receptors: Role in skin health and appearance of photoaged skin. In: Farage, M.A., Miller, K.W. and Maibach, H.I. (eds), Textbook of Aging Skin. Springer, Berlin, Heidelberg.
Di-Poï, N., Michalik, L., Desvergne, B. and Wahli, W. (2004). Functions of peroxisome proliferator-activated receptors (PPAR) in skin homeostasis. Lipids 39 1093-1099.
Schmuth, M., Moosbrugger-Martinz, V., Blunder, S. and Dubrac, S. (2014). Role of PPAR, LXR and PXR in epidermal homeostasis and inflammation. Biochimica et Biophysica Acta (BBA)—Molecular and Cell Biology of Lipids, vol 1841, issue 3, pp 463-473.