Regulation of Lipid Metabolism in Human Sebaceous Glands

Project: Research project

Project Details

Description

DESCRIPTION (provided by the applicant): Acne is the most common skin disease
affecting young people. In addition to psychological distress and feelings of
low self-esteem, acne can lead to permanent facial scarring. The production of
sebum (oil) by sebaceous glands is a key factor in the development of acne.
Apart from isotretinoin and hormonal therapy, there are no drugs that
effectively reduce sebum production. Unfortunately, these drugs have
significant side effects, including birth defects. No recent advances have been
made in our ability to therapeutically reduce sebum production in part due to
our lack of knowledge regarding the mechanisms regulating human sebum
production. The overall goal of this research is to elucidate the mechanisms
that regulate human sebum production in order to identify novel therapeutic
target sites whose pharmacological ligands will offer safe and effective
alternatives to isotretinoin for the treatment of acne. Peroxisome
proliferator-activated receptors (PPARs) and sterol response element binding
proteins (SREBPs) are key transcriptional regulators of lipid metabolism in a
variety of tissues. The central hypothesis to be tested is that PPARs regulate
lipid metabolism in human sebaceous glands. The effects of linoleic acid and
other PPAR agonists on lipid metabolism will be determined using assays of
lipid transport, synthesis, and catabolism in addition to an analysis of gene
expression. 13-cis retinoic acid is the most potent sebosuppressive agent.
PPARs and retinoids share common DNA binding sites, and in this regard can
mediate transcription of common genes. Our secondary hypothesis is that 13-cis
retinoic acid reduces sebum production by altering the expression of
PPAR-regulated genes. The effects of 13-cis retinoic acid on gene expression
will be examined in human sebocytes and in skin from patients treated with
isotretinoin. Data generated from the proposed experiments will advance our
understanding of the mechanisms regulating sebum production and can lead to
identification of potential additional therapeutic target sites in the
treatment of acne.
StatusFinished
Effective start/end date4/1/023/31/03

Funding

  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $287,450.00

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