Increased hypothalamic eCB ‘tone’ in Magel2-null mice. Hypothalamic AEA (A), 2-AG (B), and AA (C), levels in Magel2-null mice and littermate controls fed either STD (left) or HFD (right). A significant upregulation in the mRNA (D), and protein (E–G) expression levels of CB1R were measured in Magel2-null mice under both diets (STD, D, E, G; HFD, D, F, G), suggesting an increased eCB ‘tone’ in the hypothalamus. Data represent the mean ± SEM from 12 to 21 mice per group. *P < 0.05 relative to wild-type controls of the same diet. #P < 0.05 relative to the same genotype on STD.