Copyright © 2015 by the American Osteopathic Association. From: The Endocannabinoid System as a Novel Approach for Managing Obesity J Am Osteopath Assoc. 2007;107(4_suppl_2):S12-S20. Figure Legend: Synthesis, action, and degradation of endocannabinoids in neurons. Diet-derived ω6-polyunsaturated fatty acids (ω6-PUFAs) are incorporated into membrane phospholipids, which membrane enzymes then metabolize into the endocannabinoids arachidonoylglycerol (2-AG) and anandamide. Degradative enzymes for endocannabinoids are localized to internal membranes. Leptin signaling influences 2-AG biosynthesis and anandamide hydrolysis. Cannabinoid receptor 1 (CB1) is mostly in presynaptic neurons, allowing for retrograde action of endocannabinoids. Endocannabinoid action leads to a sequence of events that results in increased activity of the postsynaptic neurons. CART indicates cocaine-amphetamine-regulated transcript; CRH, corticotropin-releasing hormone; DAGL, sn-1 selective diacylglycerol lipase; EMT, putative endocannabinoid membrane transporters; FAAH, fatty acid amide hydrolase; MAGL, monoacylglycerol lipase; NAPE-PLD, N-acyl-phosphatidylethanolamine-selective phospholipase D; NArPE, N-arachidonoyl-phosphatidylethanolamine. (Reprinted with permission from Di Marzo V, Matias I. Endocannabinoid control of food intake and energy balance [review]. Nat Neurosci. 2005;8:585-589. Date of download: 11/15/2017 Copyright © 2015 by the American Osteopathic Association. All rights reserved.