Activation of adipose tissue cannabinoid receptors 1 (CB1R) alters antilipolytic action of insulin and increases lipolysis in mice

Acute activation of cannabinoid receptors by anandamide reduces gastrointestinal motility and improves postprandial glycemia in mice.

International audience; The endocannabinoid system (ECS) is associated with an alteration of glucose homeostasis dependent on cannabinoid receptor-1 (CB1R) activation. However, very little information is available concerning the consequences of ECS activation on intestinal glucose absorption. Mice were injected intraperitoneally with anandamide, an endocannabinoid binding both CB1R and CB2R. We measured plasma glucose and xylose appearance after oral loading, gastrointestinal motility, and glucose transepithelial transport using the everted sac method. Anandamide improved hyperglycemia after oral glucose charge whereas glucose clearance and insulin sensitivity were impaired, pointing out so…

Overactivation of the endocannabinoid system alters the antilipolytic action of insulin in mouse adipose tissue.

Evidence has accumulated that obesity-related metabolic dysregulation is associated with overactivation of the endocannabinoid system (ECS), which involves cannabinoid receptor 1 (CB1R), in peripheral tissues, including adipose tissue (AT). The functional consequences of CB1R activation on AT metabolism remain unclear. Since excess fat mobilization is considered an important primary event contributing to the onset of insulin resistance, we combined in vivo and in vitro experiments to investigate whether activation of ECS could alter the lipolytic rate. For this purpose, the appearance of plasma glycerol was measured in wild-type and CB1R−/− mice after acute anandamide administration or inh…

Early Low-Fat Diet Enriched With Linolenic Acid Reduces Liver Endocannabinoid Tone and Improves Late Glycemic Control After a High-Fat Diet Challenge in Mice.

International audience; Evidence suggests that alterations of glucose and lipid homeostasis induced by obesity are associated with the elevation of endocannabinoid tone. The biosynthesis of the two main endocannabinoids, N-arachidonoylethanolamine and 2-arachidonoyl-glycerol, which derive from arachidonic acid, is influenced by dietary fatty acids (FAs). We investigated whether exposure to n-3 FA at a young age may decrease tissue endocannabinoid levels and prevent metabolic disorders induced by a later high-fat diet (HFD) challenge. Three-week-old mice received a 5% lipid diet containing lard, lard plus safflower oil, or lard plus linseed oil for 10 weeks. Then, mice were challenged with a…

O45 L’activation des récepteurs aux endocannabinoïdes CB1R du tissu adipeux inhibe l’action anti-lipolytique de l’insuline

Introduction Il est maintenant bien etabli que l’obesite est associee a une suractivation du systeme endocannabinoide (SEC). Des travaux recents suggerent que le blocage des recepteurs aux endocannabinoides 1 (CB1R) peripheriques conduit a une amelioration du metabolisme glucidique et lipidique independamment des effets centraux modulant la prise alimentaire. Le role du SEC dans le tissu adipeux etant encore mal defini, cette etude vise a preciser les consequences de l’activation des CB1R sur la lipolyse. Materiels et methodes Les effets de l’anandamide (endocannabinoide) sur l’activite lipolytique estimee par la production de glycerol plasmatique ont ete testes chez la souris in vivo apres…

P259 Identification de nouveaux antagonistes des récepteurs aux endocannabinoïdes à action périphérique susceptibles d’améliorer les paramètres glucido-lipidiques chez la souris obèse

Introduction Le systeme endocannabinoide (SEC) est une cible therapeutique potentielle pour lutter contre l’obesite. Ainsi, le Rimonabant®, un antagoniste des recepteurs aux endocannabinoides 1 (CB1R) diminue la masse corporelle et ameliore les parametres glucido-lipidiques de patients obeses. Neanmoins, ce medicament a ete retire du marche suite a des effets centraux induisant des troubles neuropsychiatriques. L’objectif de cette etude est d’identifier des analogues du Rimonabant® a action peripherique susceptibles d’avoir des effets benefiques sur le metabolisme glucido-lipidique de la souris. Materiels et methodes Des analogues du Rimonabant® ne passant pas la barriere hemato-encephaliqu…