Divergent effects of central melanocortin signalling on fat and sucrose preference in humans

Melanocortin-4-receptor (MC4R)-expressing neurons modulate food intake and preference in rodents but their role in human food preference is unknown. Here we show that compared with lean and weight-matched controls, MC4R deficient individuals exhibited a markedly increased preference for high fat, but a significantly reduced preference for high sucrose food. These effects mirror those in Mc4r null rodents and provide evidence for a central molecular circuit influencing human macronutrient preference. Hypothalamic melanocortin-4-receptors (MC4R) regulate food preference in rodents, but their role in humans is unclear. Here, the authors perform food preference and liking tests in humans with MC4R mutations and find that they prefer fatty food more, but sweet food less, than people without MC4R mutations.