Fig. 9.
Prostaglandin F2α ethanolamide (PGF2αEA) and bimatoprost (Bim) potential effects. A chain of discoveries resulted from research on the endocannabinoid system (eCBS). The discovery that certain Cannabis sativa phytocannabinoids activate the body cannabinoid receptors CB1 and CB2 had directed researchers to discover the eCBS and the endocannabinoids (eCBs), as AEA (93, 94). PGF2αEA is an eCB (AEA) bioactive metabolite, which belongs to the wider lipid signaling network—the endocannabinoidome (eCBome) (34). This paper adds a new ring to the eCBome cognizance chain to ring a bell about its noteworthy roles. We showed that the chief eCB mediator AEA metabolite PGF2αEA induces preadipocyte proliferation and inhibits PPARG activity, in a mitogen-activated protein kinase kinase (MAPKK)-dependent fashion, which complements our previous discovery of its anti-adipogenic effect (21). We suggest that PGF2αEA might favor healthier fat storage and white fat plasticity, to outbalance obesity complications driver—hypertrophy (17). We parallelly showed that its pharmaceutical analog Bim presented similar effects, which might provide support in explaining the quick recovery of ocular fat pads with drug cessation. It is time o’clock to recognize and update our pathophysiology books to include the eCBome (34), especially to further revive obesity research (23, 24, 95, 96, 97, 98). We further emphasize the potential power of the research virtuous circle; clinical observation-research-discovery-clinical application, both within the same discipline and also beyond it to link relatively unrelated disciplines, such as ophthalmology and obesity research (53, 99), to guide towards more efficient multidisciplinary and interdisciplinary discoveries. This figure and the graphical abstract were created with BioRender.com and with MindtheGraph.com. Fig. 9 ink bottle icon was made by Luvdat from www.flaticon.com. AEA, N-arachidonoyl-ethanolamine; PPARG, peroxisome proliferator-activated receptor gamma.