Relation Between Pregnenolone Endocannabinoids in Normal-weight and Obese Men

Relation Between Pregnenolone Endocannabinoids in Normal-weight and Obese Men

Measured plasmatic concentration of pregnenolone and endocannabinoid in fasting conditions and over a meal in obese and normal-weight men subjects, to research a dysfunction in the negative feed-back between pregnenolone and CB1 ligand in obese subjects. This dysfunction could participate to the hyperactivity of endocannabinoid system saw in obesity.

Endocannabinoid system is an orexigenic key system, controlling the energy balance. It is composed of receptors (ex: CB1), of endogenous ligands, the endocannabinoids (ex: anandamide and 2- arachidonoylglycerol) and of enzymes implied in the synthesis and the degradation of the endocannabinoids. Researches resulting from our group highlighted anomalies of the plasmatic concentrations of endocannabinoid, in obese subject compared to normal-weight subject. Those being higher in obese subject with a flatness of post prandial reduction of AEA, so maintenance of elevated levels which can facilitate the food catch and create a metabolic vicious circle. In addition, prestigious research resulting from our collaborators highlighted in the animal that exposure to tetrahydrocannabinol (THC, ligand exogenic of CB1) induced the synthesis of pregnenolone (neurosteroid) which, by an autocrine effect on the CB1, inhibited the effects of the THC. In particular one of the principal behavioural effects: the food intake.

We want to measure pregnenolone and endocannabinoid concentrations in men blood samples, to observe if this association exists in fasting conditions and over a meal in normal-weight and obese subjects. Obese subjects will be recruited during an hospitalization, while normal subject will be recruited by a poster at Bordeaux university and Haut-Leveque hospital. They will be included at Haut-Leveque hospital during morning at hospital.

Inclusion Criteria:

• Obese subjects:

  • men,
  • aged between 18 and 65 years,
  • BMI>30kg/m2.

• Normal-weight subjects:

  • men,
  • aged between 18 and 65 years,
  • BMI<25kg/m2.

Exclusion Criteria:

• For all subjects:

  • cannabis detected by urinary tetrahydrocannabinol presence,
  • treatment which can interfere with endocannabinoid system (antidepressant, antipsychotics, anxiolytics).