Melanin-concentrating hormone and food intake control: Sites of action, peptide interactions, and appetition

•MCH increases food intake, acting in discreet hypothalamic nuclei, the nucleus accumbens, and cerebrospinal fluid.•Melanin-concentrating hormone interacts with a number of neuropeptides resulting in metabolic consequences.•The orexigenic effect of melanin-concentrating hormone is sex-dependent and likely mediated by estrogen receptor-α.•Melanin-concentrating hormone may be involved in early prandial “appetition” that enhances consumption within a meal. Given the increased prevalence of obesity and its associated comorbidities, understanding the mechanisms through which the brain regulates energy balance is of critical importance. The neuropeptide melanin-concentrating hormone (MCH) is produced in the lateral hypothalamic area and the adjacent incerto-hypothalamic area and promotes both food intake and energy conservation, overall contributing to body weight gain. Decades of research into this system has provided insight into the neural pathways and mechanisms (behavioral and neurobiological) through which MCH stimulates food intake. Recent technological advancements that allow for selective manipulation of MCH neuron activity have elucidated novel mechanisms of action for the hyperphagic effects of MCH, implicating neural “volume” transmission in the cerebrospinal fluid and sex-specific effects of MCH on food intake control as understudied areas for future investigation. Highlighted here are historical and recent findings that illuminate the neurobiological mechanisms through which MCH promotes food intake, including the identification of various specific neural signaling pathways and interactions with other peptide systems. We conclude with a framework that the hyperphagic effects of MCH signaling are predominantly mediated through enhancement of an “appetition” process in which early postoral prandial signals promote further caloric consumption.