Peroxisome proliferator-activated receptors increase human sebum production

Nishit R. Trivedi, Zhaoyuan Cong, Amanda M. Nelson, Adam J. Albert, Lorraine L. Rosamilia, Surendra Sivarajah, Kathryn L. Gilliland, Wenlei Liu, David T. Mauger, Robert A. Gabbay, Diane M. Thiboutot

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

Sebum production is key in the pathophysiology of acne, an extremely common condition, which when severe, may require treatment with isotretinoin, a known teratogen. Apart from isotretinoin and hormonal therapy, no agents are available to reduce sebum. Increasing our understanding of the regulation of sebum production is a milestone in identifying alternative therapeutic targets. Studies in sebocytes and human sebaceous glands indicate that agonists of peroxisome proliferator-activated receptors (PPARs) alter sebaceous lipid production. The goal of this study is to verify the expression and activity of PPARs in human skin and SEB-1 sebocytes and to assess the effects of PPAR ligands on sebum production in patients. To investigate the contribution of each receptor subtype to sebum production, lipogenesis assays were performed in SEB-1 sebocytes that were treated with PPAR ligands and isotretinoin. Isotretinoin significantly decreased lipogenesis, while the PPARα agonist-GW7647, PPARδ agonist-GW0742, PPARα/δ agonist-GW2433, PPARγ agonist rosiglitazone, and the pan-agonist-GW4148, increased lipogenesis. Patients treated with thiazolidinediones or fibrates had significant increases in sebum production (37 and 77%, respectively) when compared to age-, disease-, and sex-matched controls. These data indicate that PPARs play a role in regulating sebum production and that selective modulation of their activity may represent a novel therapeutic strategy for the treatment of acne.

Original languageEnglish (US)
Pages (from-to)2002-2009
Number of pages8
JournalJournal of Investigative Dermatology
Volume126
Issue number9
DOIs
StatePublished - Sep 1 2006

Fingerprint

Sebum
Peroxisome Proliferator-Activated Receptors
Isotretinoin
Lipogenesis
rosiglitazone
Acne Vulgaris
Ligands
Teratogens
Fibric Acids
Therapeutics
Sebaceous Glands
Thiazolidinediones
Assays
Skin
Modulation
Lipids

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Trivedi, Nishit R. ; Cong, Zhaoyuan ; Nelson, Amanda M. ; Albert, Adam J. ; Rosamilia, Lorraine L. ; Sivarajah, Surendra ; Gilliland, Kathryn L. ; Liu, Wenlei ; Mauger, David T. ; Gabbay, Robert A. ; Thiboutot, Diane M. / Peroxisome proliferator-activated receptors increase human sebum production. In: Journal of Investigative Dermatology. 2006 ; Vol. 126, No. 9. pp. 2002-2009.
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abstract = "Sebum production is key in the pathophysiology of acne, an extremely common condition, which when severe, may require treatment with isotretinoin, a known teratogen. Apart from isotretinoin and hormonal therapy, no agents are available to reduce sebum. Increasing our understanding of the regulation of sebum production is a milestone in identifying alternative therapeutic targets. Studies in sebocytes and human sebaceous glands indicate that agonists of peroxisome proliferator-activated receptors (PPARs) alter sebaceous lipid production. The goal of this study is to verify the expression and activity of PPARs in human skin and SEB-1 sebocytes and to assess the effects of PPAR ligands on sebum production in patients. To investigate the contribution of each receptor subtype to sebum production, lipogenesis assays were performed in SEB-1 sebocytes that were treated with PPAR ligands and isotretinoin. Isotretinoin significantly decreased lipogenesis, while the PPARα agonist-GW7647, PPARδ agonist-GW0742, PPARα/δ agonist-GW2433, PPARγ agonist rosiglitazone, and the pan-agonist-GW4148, increased lipogenesis. Patients treated with thiazolidinediones or fibrates had significant increases in sebum production (37 and 77{\%}, respectively) when compared to age-, disease-, and sex-matched controls. These data indicate that PPARs play a role in regulating sebum production and that selective modulation of their activity may represent a novel therapeutic strategy for the treatment of acne.",
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Trivedi, NR, Cong, Z, Nelson, AM, Albert, AJ, Rosamilia, LL, Sivarajah, S, Gilliland, KL, Liu, W, Mauger, DT, Gabbay, RA & Thiboutot, DM 2006, 'Peroxisome proliferator-activated receptors increase human sebum production', Journal of Investigative Dermatology, vol. 126, no. 9, pp. 2002-2009. https://doi.org/10.1038/sj.jid.5700336

Peroxisome proliferator-activated receptors increase human sebum production. / Trivedi, Nishit R.; Cong, Zhaoyuan; Nelson, Amanda M.; Albert, Adam J.; Rosamilia, Lorraine L.; Sivarajah, Surendra; Gilliland, Kathryn L.; Liu, Wenlei; Mauger, David T.; Gabbay, Robert A.; Thiboutot, Diane M.

In: Journal of Investigative Dermatology, Vol. 126, No. 9, 01.09.2006, p. 2002-2009.

Research output: Contribution to journalArticle

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AU - Trivedi, Nishit R.

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AU - Albert, Adam J.

AU - Rosamilia, Lorraine L.

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