Obesity, classified as a chronic disease by the World Health Organization (WHO) is regarded as having irregular or excessive fat accumulation. It can be measured and quantified by examining ones body mass index (BMI), where on average, anyone over 30kg/m2 would be classified as obese (WHO 2012). Obesity is followed by a large number of health risks (including diabetes, cardiovascular diseases, cancer and more) and generally decreases life expectancy. What has been discovered recently is that genetics plays a large role in obesity, specifically the role of melanocortin 4 receptors (MC4R) and how dysfunction of the receptors can lead to an onset of obesity (Logan MG et al. 2010).
Although obesity is commonly known to be caused by the imbalance in calorie consumption and energy output, recent research has illustrated the genetic factor that can be taken into account for certain individuals, therefore making obesity a multi-factorial disease. MC4R has largely been known to maintain energy homeostasis by regulating the body’s food intake. It does so by providing an anorexigenic signal, which is a result of the binding of an agonist (alpha-melanocyte-stimulating hormone) to the receptor, allowing one to have the sensation of being full (Logan MG et al. 2010). Due to the multiple mutations that MC4R is susceptible to some individuals will be more likely to become obese than others with the pathogenic MC4R. MC4R polymorphisms do not actually impair an individual’s rate of energy expenditure, but rather affects their appetite causing a hyperphagic state. Phenotypes that usually follow this kind of mutation include increase in fat or growth, eating disorders (binge-eating) and hyperinsulinaemia (abnormally high levels of insulin circulation). The reason that MC4R polymorphisms result in such phenotypes is largely due to the hindered functionality of the MC4 receptor (Logan MG et al. 2010). Mutated MC4R is observed to have decreased or absent ligand binding, decreased cell surface receptor expression, incorrect protein formation, and reduced signal transduction. Of these defects, those that interfere with intracellular reception (compromises the functionality and activity of the receptors) are linked to more severe forms of obesity. This allows fairly accurate predictions to be made about the onset and severity of obesity in people with pathogenic MC4R mutations. More importantly, carriers of pathogenic MC4R have an 82% chance of passing it onto their offspring, increasing the odds of being obese by almost 5 times (note that ethnicity is also a variable) (Logan MG et al. 2010). Lastly, the polymorphism or mutation that can be identified in the MC4R gene does not imply that either the mutation is involved in the pathogenesis of the disease and that the subject will have the observed phenotypes.
There are simply too many factors that can come into account when attempting to overcome such an epidemic as obesity; however by understanding how genetics affects obesity treatments can be enhanced and diversified to create more effective treatments for patient. By being able to predict such abnormalities through the mutations of MC4R, obesity can be prevented before onset. Theorized treatments aim to suppress appetite by increasing neural sensitivity to insulin and leptin; however current research has yet to bring forth concrete solutions to this disease (Christian N 2012).