Palomares, BelenRuiz-Pino, FranciscoNavarrete, CarmenVelasco, InmaculadaSanchez-Garrido, Miguel AJimenez-Jimenez, CarlaPavicic, CarolinaVazquez, Maria JAppendino, GiovanniBellido, M LuzCalzado, Marco ATena-Sempere, ManuelMuñoz, Eduardo2023-01-252023-01-252018-10-06Palomares B, Ruiz-Pino F, Navarrete C, Velasco I, Sánchez-Garrido MA, Jimenez-Jimenez C, et al. VCE-004.8, A Multitarget Cannabinoquinone, Attenuates Adipogenesis and Prevents Diet-Induced Obesity. Sci Rep. 2018 Oct 31;8(1):16092http://hdl.handle.net/10668/13145Over the past few years, the endocannabinoid system (ECs) has emerged as a crucial player for the regulation of food intake and energy metabolism, and its pharmacological manipulation represents a novel strategy for the management of metabolic diseases. The discovery that VCE-004.8, a dual PPARγ and CB2 receptor agonist, also inhibits prolyl-hydroxylases (PHDs) and activates the HIF pathway provided a rationale to investigate its effect in in vitro models of adipogenesis and in a murine model of metabolic syndrome, all processes critically regulated by these targets of VCE-004.8. In accordance with its different binding mode to PPARγ compared to rosiglitazone (RGZ), VCE-004.8 neither induced adipogenic differentiation, nor affected osteoblastogenesis. Daily administration of VCE-004.8 (20 mg/kg) to HFD mice for 3-wks induced a significant reduction in body weight gain, total fat mass, adipocyte volume and plasma triglycerides levels. VCE-004.8 could also significantly ameliorate glucose tolerance, reduce leptin levels (a marker of adiposity) and increase adiponectin and incretins (GLP-1 and GIP) levels. Remarkably, VCE-004.8 increased the FGF21 mRNA expression in white and brown adipose, as well as in a BAT cell line, qualifying cannabinoaminoquinones as a class of novel therapeutic candidates for the management of obesity and its common metabolic co-morbidities.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Cell differentiationDiet, high-fatFeeding behaviorFibroblast growth factorsHEK293 cellsAdipogenesisAdiposityAnimalsBiomarkersBody compositionCannabidiolHormonesHumansInsulin resistanceMaleMice, inbred C57BLObesityOsteoblastsPPAR gammaWeight gainresearch article30382123open accessAdipogénesisAdiposidadAumento de pesoBiomarcadoresComposición corporalObesidadResistencia a la insulina10.1038/s41598-018-34259-02045-2322PMC6208444https://www.nature.com/articles/s41598-018-34259-0.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208444/pdf