Eating behaviour in obese patients with melanocortin-4 receptor mutations: a literature review

Abstract

Melanocortin-4 receptor (MC4R) mutations are the most common known cause of monogenic obesity and an important contributor to polygenic obesity. MC4R mutations with partial or total loss of function, as well as the variant rs17782313 mapped near MC4R, are positively associated with obesity. MC4R is involved in the leptin-melanocortin signalling system, located in hypothalamic nuclei, that controls food intake via both anorexigenic or orexigenic signals. Impairment in this receptor might affect eating behaviours. Thus, in the case of MC4R mutation carriers, obesity could be related, at least partly, to inadequate control over eating behaviours. Many published studies address eating behaviours in MC4R mutation carriers. Most studies focus on binge eating disorder, whereas others examine various aspects of intake and motivation. Up to now, no evaluation of this literature has been performed. In this review, we examine the available literature on eating behaviours in carriers of MC4R mutations and variant rs17782313 near MC4R gene. We address binge eating disorder, bulimia nervosa, mealtime hyperphagia, snacking, psychological factors, satiety responsiveness and intake of energy and macro/micronutrient. In a small number of studies, MC4R mutations seem to impair eating behaviours or motivation, but no clear causal effects can be found in the balance of the evidence presented. Improvements in methodologies will be necessary to clarify the behavioural effects of MC4R mutations.

Melanocortin-4 Receptor Gene Variation Is Associated with Eating Behavior in Chilean Adults

“…The frequencies shown in our research are slightly different than those in European populations. For example, the MC4R rs17782313T>C polymorphism in Chile shows slightly lower frequency than that in the French and Swiss population, slightly higher than that in the Finnish population and similar to that of the Spanish population [38,39] . Differences in allele frequencies by obesity categories in our study are in accordance to other studies [38,39] .…”

Cognitive and autonomic determinants of energy homeostasis in obesity

“…96 In patients with obesity, the prevalence of pathogenic Mc4r mutations ranges from 1% to 6%. 97,98 In mice, the excess of fat storage that occurs in Mc4r-deficient mutants results from an enhanced energy intake 96 and a reduced energy expenditure. 99 The view that MC4R controls both energy intake and expenditure is also supported by pharmacological and physiological studies in which MC4R agonists can reduce food intake and stimulate energy expenditure via SNS-mediated thermogenesis of BAT.…”

Association of melanocortin 4 receptor gene variation with satiation and gastric emptying in overweight and obese adults

“…The average increase in BMI was 0.22 kg/m 2 . The polymorphism rs17782313 is associated with satiety in American, European, and Chilean children (Beckers et al 2011;Czerwensky et al 2013;Qi et al 2008;Stutzmann et al 2009;Valladares et al 2010;Xi et al 2012) as well as with higher intake of total calories, fat, and protein (Beckers et al 2011;Loos 2011;Qi et al 2008;Scherag et al 2010;Valette et al 2013). In a systematic review of 61 studies (involving 80,957 obese and 220,223 controls), rs17782313 polymorphism was significantly associated with obesity risk (OR 1.18, 95 % CI 1.15-1.21, p = 0.001) (Xi et al 2012).…”