VCE-004.8, A Multitarget Cannabinoquinone, Attenuates Adipogenesis and Prevents Diet-Induced Obesity

Sci Rep. 2018 Oct 31;8(1):16092. doi: 10.1038/s41598-018-34259-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis / drug effects*
  • Adiposity / drug effects
  • Animals
  • Biomarkers / metabolism
  • Body Composition / drug effects
  • Cannabidiol / pharmacology
  • Cannabidiol / therapeutic use*
  • Cell Differentiation / drug effects
  • Diet, High-Fat
  • Feeding Behavior
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism
  • HEK293 Cells
  • Hormones / metabolism
  • Humans
  • Insulin Resistance
  • Male
  • Mice, Inbred C57BL
  • Obesity / drug therapy*
  • Obesity / prevention & control*
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • PPAR gamma / agonists
  • PPAR gamma / metabolism
  • Weight Gain / drug effects


  • Biomarkers
  • Hormones
  • PPAR gamma
  • fibroblast growth factor 21
  • Cannabidiol
  • Fibroblast Growth Factors