RT Journal Article
T1 VCE-004.8, A Multitarget Cannabinoquinone, Attenuates Adipogenesis and Prevents Diet-Induced Obesity.
A1 Palomares, Belen
A1 Ruiz-Pino, Francisco
A1 Navarrete, Carmen
A1 Velasco, Inmaculada
A1 Sanchez-Garrido, Miguel A
A1 Jimenez-Jimenez, Carla
A1 Pavicic, Carolina
A1 Vazquez, Maria J
A1 Appendino, Giovanni
A1 Bellido, M Luz
A1 Calzado, Marco A
A1 Tena-Sempere, Manuel
A1 Muñoz, Eduardo
K1 Cell differentiation
K1 Diet, high-fat
K1 Feeding behavior
K1 Fibroblast growth factors
K1 HEK293 cells
AB 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.
PB Nature Publishing Group
YR 2018
FD 2018-10-06
LK http://hdl.handle.net/10668/13145
UL http://hdl.handle.net/10668/13145
LA en
NO Palomares 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):16092
NO Tis work was supported by grants SAF2014-53763-P, SAF2017-87701-R (EM) and BFU2014-57581-P and BFU2017-83934-P (M.T.-S.) (Ministerio de Economía y Competitividad, Spain; co-funded with EU funds fromFEDER Program); Project PIE14-00005 (Flexi-Met, Instituto de Salud Carlos III, Ministerio de Sanidad, Spain); Project P12-FQM-01943 (M.T.-S.; Junta de Andalucía, Spain). CIBER Fisiopatología de la Obesidad y Nutrición isan initiative of Instituto de Salud Carlos III. Senior authors are indebted with Prof. Francesc Villarroya (University of Barcelona, Spain) and Prof. Angela M. Valverde (Instituto de Investigaciones Biomedicas Alberto Sols, Madrid,Spain) for provision of the pBAT cell line, important for conduction of some of the experiments included in this study. None of the funding bodies played any role in the study design, data collection and analysis, the decisionto publish, or the preparation of the manuscript. BP is a predoctoral fellow supported by the i-PFIS program, Instituto de Salud Carlos III (IFI15/00022; European Social Fund “investing in your future”).
DS RISalud
RD Apr 9, 2025