PMID- 24508785 OWN - NLM STAT- MEDLINE DCOM- 20140506 LR - 20220330 IS - 1552-5783 (Electronic) IS - 0146-0404 (Linking) VI - 55 IP - 3 DP - 2014 Mar 4 TI - Activation of the prostanoid FP receptor inhibits adipogenesis leading to deepening of the upper eyelid sulcus in prostaglandin-associated periorbitopathy. PG - 1269-76 LID - 10.1167/iovs.13-12589 [doi] AB - PURPOSE: 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 (PGF2alpha) 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 PGF2alpha 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 PGF2alpha significantly suppressed adipogenesis (P < 0.05). In mouse primary adipocyte cultures, LAT-A, TAF-A, BIM-A, TRA-A, and PGF2alpha 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. FAU - Taketani, Yukako AU - Taketani Y AD - Department of Ophthalmology, University of Tokyo, Tokyo, Japan. FAU - Yamagishi, Reiko AU - Yamagishi R FAU - Fujishiro, Takashi AU - Fujishiro T FAU - Igarashi, Masaki AU - Igarashi M FAU - Sakata, Rei AU - Sakata R FAU - Aihara, Makoto AU - Aihara M LA - eng PT - Journal Article DEP - 20140304 PL - United States TA - Invest Ophthalmol Vis Sci JT - Investigative ophthalmology & visual science JID - 7703701 RN - 0 (Prostaglandins, Synthetic) RN - 0 (Receptors, Prostaglandin) RN - 0 (prostaglandin F2alpha receptor) SB - IM MH - Adipocytes/drug effects/pathology MH - Adipogenesis/*drug effects MH - Animals MH - Cells, Cultured MH - Disease Models, Animal MH - Eyelids/*drug effects/pathology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Orbit/*pathology MH - Orbital Diseases/chemically induced/*metabolism/pathology MH - Prostaglandins, Synthetic MH - Receptors, Prostaglandin/*metabolism OTO - NOTNLM OT - FP receptor OT - deepening of the upper eyelid sulcus OT - lipids OT - prostaglandins EDAT- 2014/02/11 06:00 MHDA- 2014/05/07 06:00 CRDT- 2014/02/11 06:00 PHST- 2014/02/11 06:00 [entrez] PHST- 2014/02/11 06:00 [pubmed] PHST- 2014/05/07 06:00 [medline] AID - iovs.13-12589 [pii] AID - 10.1167/iovs.13-12589 [doi] PST - epublish SO - Invest Ophthalmol Vis Sci. 2014 Mar 4;55(3):1269-76. doi: 10.1167/iovs.13-12589.