Activation of the prostanoid FP receptor inhibits adipogenesis leading to deepening of the upper eyelid sulcus in prostaglandin-associated periorbitopathy.
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 (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.
['Taketani|Yukako|Y|', 'Yamagishi|Reiko|R|', 'Fujishiro|Takashi|T|', 'Igarashi|Masaki|M|', 'Sakata|Rei|R|', 'Aihara|Makoto|M|']
D017667:Adipocytes D050156:Adipogenesis D000818:Animals D002478:Cells, Cultured D004195:Disease Models, Animal D005143:Eyelids D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D009915:Orbit D009916:Orbital Diseases D011465:Prostaglandins, Synthetic D011982:Receptors, Prostaglandin
FP receptor deepening of the upper eyelid sulcus prostaglandins lipids