2-arachidonoylglycerol signaling in forebrain regulates systemic energy metabolism

摘要: The endocannabinoid system plays a critical role in the control of energy homeostasis, but identity and localization signal involved remain unknown. In present study, we developed transgenic mice that overexpress forebrain neurons presynaptic hydrolase, monoacylglycerol lipase (MGL), which deactivates 2-arachidonoyl-sn-glycerol (2-AG). MGL-overexpressing show 50% decrease 2-AG levels no overt compensation other components. This biochemical abnormality is accompanied by series metabolic changes include leanness, elevated cost activity, hypersensitivity to β(3)-adrenergic-stimulated thermogenesis, corrected reinstating activity at CB(1)-cannabinoid receptors. Additionally, mutant are resistant diet-induced obesity express high thermogenic proteins, such as uncoupling protein 1, their brown adipose tissue. results suggest signaling through CB(1) regulates neural circuits dissipation.