Abstract
CONTEXT:
Obesity is associated with a low-grade inflammatory state, and adipocyte hyperplasia/hypertrophy. Obesity inhibits the “browning” of white adipose tissue. Cannabinoid receptor 2 (CB2) agonists reduce food intake and induce anti-obesity effect in mice. A common missense CB2-variant, Q63R, causes CB2 reduced function.
OBJECTIVE:
To evaluate the influence of CB2 receptor on the modulation of childhood obesity and of adipocyte activity and morphology.
DESIGN:
CB2-Q63R variant was analyzed in obese Italian children. The effects of an inflammatory stimulus and those of drugs selectively acting on CB2 were investigated on in-vitro adipocytes obtained from mesenchymal stem cells of adult healthy donors or from subcutaneous adipose biopsies of adult non-obese and obese subjects.
SETTING:
Department of Women, Child and General and Specialist Surgery of the Second University of Naples.
PATIENTS OR OTHER PARTICIPANTS:
Five hundred and one obese Italian children (age 11±2.75). Twelve healthy bone marrow donors (age 36.5±15). Seventeen subjects, 7 lean (age 42±10) and 10 obese (age 37.8±12), underwent subcutaneous adipose tissue biopsies.
MAIN OUTCOME MEASURES:
Effects of CB2 stimulation on adipokine, perilipin and UCP-1 expression.
RESULTS:
The less-functional CB2-R63 variant was significantly associated with a high z-score BMI. CB2 blockade with AM630 reverse agonist increased inflammatory adipokine release and fat storage and reduced browning. CB2 stimulation with JWH-133 agonist reversed all of the obesity-related effects.
CONCLUSION:
CB2 receptor is a novel pharmacological target that should be considered for obesity.
- PMID: 27294325
- [PubMed – as supplied by publisher]
