The hypothalamus is a key part of the brain that helps regulate hunger; as part of this, the hormone leptin, produced by adipose (fat) tissue, falls in response to fasting. This fall in leptin leads to the brain triggering actions to restore energy balance. The melanocortin-4 receptor (MC4R) pathway is a key part of this process and a critical regulator of hunger and energy balance which helps maintain stable body weight.1
Rare MC4R pathway diseases, which lead to hyperphagia (pathological, insatiable hunger) and early-onset obesity, are distinct from general obesity.1
One of the cardinal symptoms of rare MC4R pathway diseases is hyperphagia. Hyperphagia is characterised by an overwhelming, heightened, and relentless hunger, a longer time to reach satiety, a shorter duration of satiety, and, potentially, extreme food-seeking behaviours such as waking up at night to find food. Hyperphagia leads to excess energy intake, which contributes to obesity.5,6
Obesity results from factors that disrupt the balance of energy intake (food consumption) and energy expenditure (metabolic rate, thermogenesis, and physical activity). While many environmental factors can influence this balance, our genes also significantly define our body weight. Research has shown that some naturally arising genetic variants are associated with obesity.1,6,7
- Fonseca ACP, et al., J Diabetes Complications. 2017;31(10):1549-1561
- Huvenne H, et al., Obes Facts. 2016; 9(3):158-173
- Haqq AM, et al., Lanc Diab & Endo. 2022 ; 10(12) :859-868
- Kim JH, Choi JH. Annals of Pediatric End. 2013;(18):161-167
- Heymsfield SB, et al. H. Obesity (Silver Spring). 2014
- Littleton H., et al., Mol Diagn Ther. 2020;24(6):653-663
- Yazdi F, et al. Peer J. 2015;3:e856.
- Eneli I, et al. Appl Clin Genet. 2019; 12: 87–93.