%0 Journal Article %A Palomares, Belen %A Ruiz-Pino, Francisco %A Navarrete, Carmen %A Velasco, Inmaculada %A Sanchez-Garrido, Miguel A %A Jimenez-Jimenez, Carla %A Pavicic, Carolina %A Vazquez, Maria J %A Appendino, Giovanni %A Bellido, M Luz %A Calzado, Marco A %A Tena-Sempere, Manuel %A Muñoz, Eduardo %T VCE-004.8, A Multitarget Cannabinoquinone, Attenuates Adipogenesis and Prevents Diet-Induced Obesity. %D 2018 %U http://hdl.handle.net/10668/13145 %X Over 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. %K Cell differentiation %K Diet, high-fat %K Feeding behavior %K Fibroblast growth factors %K HEK293 cells %~