title: Adapalene suppresses sebum accumulation via the inhibition of triacylglycerol biosynthesis and perilipin expression in differentiated hamster sebocytes in vitro.
abstract: BACKGROUND
  Acne is a chronic inflammatory disease in sebaceous glands and pilosebaceous units where excess sebum production and follicular hyperkeratinization are observed. Adapalene, which exerts comedolytic and anti-inflammatory effects, is used for the topical treatment of mild to moderate acne.
  
  
  OBJECTIVE
  We examined the effect of adapalene on sebum production and accumulation in sebaceous gland cells (sebocytes).
  
  
  METHODS
  The regulation of sebum production was examined by oil red O and nile red staining and the measurement of triacylglycerols (TGs) in differentiated hamster sebocytes. The gene expression and production of diacylglycerol acyltransferase-1 (DGAT-1) and perilipin 1 (PLIN1) were analyzed using real-time PCR and Western blotting, respectively.
  
  
  RESULTS
  Adapalene suppressed sebum accumulation as lipid droplets in spontaneously and insulin-differentiated hamster sebocytes. The TG production, and the gene expression and production of DGAT-1, a rate-limiting enzyme of TG biosynthesis, were dose-dependently inhibited by adapalene in insulin-, 5α-dihydrotestosterone- or a peroxisome proliferator activating receptor γ agonist, troglitazone-differentiated hamster sebocytes. In addition, the inhibition of TG production by adapalene interfered with antagonists against nuclear retinoic acid and retinoid X receptors (CD2665 and UVI3006, respectively) in the differentiated sebocytes. Furthermore, the production of PLIN1, a lipid storage droplet protein, was transcriptionally inhibited by adapalene in the differentiated sebocytes.
  
  
  CONCLUSIONS
  These results suggest that adapalene exerts an inhibitory action for sebum accumulation due to the suppression of TG and PLIN1 production in differentiated hamster sebocytes. Furthermore, these findings may contribute to a novel understanding of the molecular mechanisms of adapalene for acne treatment and prevention.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan. satotak@toyaku.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.forename: Noriko
authors.initials: N
authors.lastname: Akimoto
authors.forename: Kimiko
authors.initials: K
authors.lastname: Kitamura
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kurihara
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Hayashi
authors.forename: Akira
authors.initials: A
authors.lastname: Ito
mesh_terms: D000068816:Adapalene; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003879:Dermatologic Agents / Q000494:pharmacology*; D051048:Diacylglycerol O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D009281:Naphthalenes / Q000494:pharmacology*; D047495:PPAR gamma / Q000187:drug effects / Q000378:metabolism; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D047490:Retinoid X Receptor alpha / Q000187:drug effects / Q000378:metabolism; D012627:Sebaceous Glands / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012629:Sebum / Q000378:metabolism*; D014280:Triglycerides / Q000096:biosynthesis*
chemical_list: D002352:Carrier Proteins; D003879:Dermatologic Agents; D009281:Naphthalenes; D047495:PPAR gamma; D000070778:Perilipin-1; D010750:Phosphoproteins; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047490:Retinoid X Receptor alpha; D014280:Triglycerides; D000068816:Adapalene; D051048:Diacylglycerol O-Acyltransferase