MC4R is a receptor that is critical to weight control. Activation of MC4R leads to weight loss and blocking it leads to weight gain. The major driving force behind obesity in modern society is overeating, which is largely coded in genes that are responsible for appetite and satiety regulation. Appetite is the desire to eat while satiety refers to the sensation of fullness after eating. MC4R is one of these genes.
MC4R codes for a protein called melanocortin 4 receptor, which is mainly found in the hypothalamus of the brain, an area responsible for controlling appetite and satiety. The human body has many sensors for energy levels. When it senses high energy levels, it sends out “satiety signals” to activate the neurons through the melanocortin 4 receptor to alert the body that it’s full. When the body senses low energy levels, “hunger signals” activate the neurons, also through the melanocortin 4 receptor, to produce the feeling of hunger.
Mutations in MC4R are the most common genetic cause of obesity. Many MC4R mutations have been documented. Some reduce gene function, some eliminate function altogether. While these mutations account for about 6-8% severe inheritable obese symptoms, they are relatively rare in the general population.
One common variant of the MC4R gene, carried by 22% of the general population, causes reduced MC4R protein level in the hypothalamus of the brain. Carriers of this variant have both increased appetite and decreased satiety. They tend to eat larger amounts of food, snack more frequently and like to eat fatty foods (ref: GB Health Watch).
A C-allele genetic variation means a decreased MC4R expression that may lead to impaired energy regulation, obesity, higher BMI, waist circumference, overeating, greater total energy intake, hyperinsulinemia, and reduced satiety. This means that in order to manage your weight, it is recommended that you use diet to control your appetite and satiety. Choose healthy snacks and make sure that they are readily on hand in the car or at your desk at work so that you don't snack on the 'wrong' foods. When considering your overall risk, it is important to consider your POMC, LEPR, PPARG, and PPARGC1 genotypes.