title: Activation of the prostanoid FP receptor inhibits adipogenesis leading to deepening of the upper eyelid sulcus in prostaglandin-associated periorbitopathy.
abstract: OBJECTIVE
  To investigate the effects of prostaglandin (PG) analogues on adipogenesis so as to clarify the mechanism of a side effect of topical PG analogues: deepening of the upper eyelid sulcus (DUES), which has been reported in this decade.
  
  
  METHODS
  The 3T3-L1 preadipocytes were treated to promote differentiation into mature adipocytes. During the early and late stages of differentiation (days 0, 2, and 7), 1 to 1000 nM latanoprost acid (LAT-A), travoprost acid (TRA-A), tafluprost acid (TAF-A), bimatoprost (BIM), bimatoprost acid (BIM-A), unoprostone (UNO), or prostaglandin F2a (PGF2α) was applied to cells. Oil red O staining was used to detect intracellular lipids on day 10. Stained areas measured on a photograph were compared with those in control cultures. All experiments were performed in a masked manner. Next, similar experiments were performed using primary cultured mouse adipocytes from FP receptor knockout and wild-type mice.
  
  
  RESULTS
  When PGs were added on day 0 or 2, LAT-A, TAF-A, BIM-A, and PGF2α significantly inhibited adipogenesis (P < 0.01 on day 0, P < 0.05 on day 2) at concentrations of 10 nM and 100 nM, and TRA-A inhibited adipogenesis only at 100 nM. Bimatoprost and UNO did not affect adipogenesis at any concentration. When PGs were added on day 7, 100 nM LAT-A, BIM-A, or PGF2α significantly suppressed adipogenesis (P < 0.05). In mouse primary adipocyte cultures, LAT-A, TAF-A, BIM-A, TRA-A, and PGF2α significantly suppressed adipogenesis in wild-type adipocytes (P < 0.05), but adipogenesis was not suppressed by any of the PG compounds in FP knockout mouse adipocytes.
  
  
  CONCLUSIONS
  Prostaglandin analogues have the potential to inhibit adipogenesis through FP receptor stimulation. Although these findings should be further analyzed in model systems more closely related to orbital fat, PG analogues may directly lead to reduced orbital fat by inhibiting adipogenesis.
authors: Department of Ophthalmology, University of Tokyo, Tokyo, Japan.
authors: Yukako
authors: Y
authors: Taketani
authors: Reiko
authors: R
authors: Yamagishi
authors: Takashi
authors: T
authors: Fujishiro
authors: Masaki
authors: M
authors: Igarashi
authors: Rei
authors: R
authors: Sakata
authors: Makoto
authors: M
authors: Aihara
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000473:pathology; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005143:Eyelids / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009915:Orbit / Q000473:pathology*; D009916:Orbital Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011465:Prostaglandins, Synthetic; D011982:Receptors, Prostaglandin / Q000378:metabolism*
chemical_list: D011465:Prostaglandins, Synthetic; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor
keywords: FP receptor; deepening of the upper eyelid sulcus; lipids; prostaglandins