The neuronal histamine H1 and pro-opiomelanocortin–melanocortin 4 receptors: Independent regulation of food intake and energy expenditure

Hypothalamic neuronal histamine and its H1 receptor (H1-R) form part of the leptin signaling pathway in the brain, and regulate body weight and adiposity by affecting food intake and energy expenditure. The pro-opiomelanocortin (POMC)–melanocortin 4 receptor (MC4-R) is also important for leptin signaling. We investigated whether and how these two neuronal pathways interact in regulating energy metabolism. From studies of agouti yellow (Ay/a) obese mice, a model of a defect in POMC–MC4-R signaling, we concluded that the histamine H1-R signaling pathway is independent of the POMC–MC4-R complex in regulating food intake, energy metabolism, and adiposity.