Ground-breaking discovery finds gene mutations promote obesity more than previously thought

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By Sophie Holman-Jones, Third Year, Biomedical Sciences

Content warning: discusses eating disorders

Researchers from the University of Bristol made a ground-breaking discovery this month, revealing that mutations in the MC4R gene promote obesity in the UK twice more than previously thought.

With global rates of obesity almost tripling since 1975, the scale of the obesity crisis is growing faster than our waistlines. Since being overweight is associated with a multitude of health problems, including cardiovascular diseases, cancers and diabetes, tackling this crisis has never been more imperative.

Over the last twenty years, genetics have been increasingly implicated in the incidence of obesity. The MC4R gene in particular has been studied, although the extent of its role in obesity has previously been elusive.

The obesity crisis is growing faster than our waistlines | Epigram / Sarah Dalton

The MC4R gene encodes the melanocortin 4 receptor, which is a part of the leptin-melanocortical system. When MC4Rs become activated, feeding is suppressed, thus the leptin-melanocortical system regulates food intake. This prevents excessive overfeeding. Unfortunately, in individuals with MC4R mutations, this process becomes dysregulated, leading to excessive food intake and obesity.

Led by Dr Kaitlin Wade, the University of Bristol researchers worked in collaboration with scientists from the University of Cambridge. Together, they aimed to quantify the number of individuals who may carry these mutations and determine how it affects various lifestyle factors as they age.

The team selected a sample of 5,724 individuals from the Bristol-based Avon Longitudinal Study of Parents and Children (ALSPAC), which follows up on various environmental and genetic characteristics throughout participants’ lives.

The team have laid the groundwork for new potential treatments for obesity

Researchers began by sequencing MC4R in these individuals and identified 29 different mutations among them, of which 27 were missense mutations. This means that the function of MC4R has changed due to a change in a single base pair, and hence a change to an amino acid.

The team estimated that 0.3 per cent of the sample group harboured MC4R mutations, which equates to one in every 337 people in the UK. This has been a landmark finding in the field, since these statistics are twice the size of those which had previously been reported.

Body mass index statistics from the ALSPAC were also used to investigate the significance of the relationship between MC4R and body weight. Evidence found that the gene does indeed contribute to an increased body mass index, with the effects starting to take hold from as early as five years of age. By the age of 18, a carrier could weigh 17.76kg more than a non-carrier of the same age.

A diagnosis does not necessarily condemn an individual to obesity

The statistics presented in the research paper are both staggering and concerning, particularly for those study participants who were diagnosed with mutated MC4R genes. However, all is not lost, as a diagnosis does not necessarily condemn an individual to obesity.

Interestingly, not all carriers sampled from the ALSPAC were obese, indicating that perhaps there are other factors at play which work in conjunction with a faulty MC4R gene in order to cause an individual to gain weight.

Therefore, if future research were able to explain what these other factors may be (such as smoking), the predisposed individuals may be able to make healthier lifestyle choices in order to reduce their risk of excessive weight gain.

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By investigating the extent of MC4R’s impact and highlighting the gene as a potential drug target, the team have laid the groundwork for new potential treatments for obesity, and thus as a means to tackle the obesity crisis. Fad-diets and exercise regimes to lose weight may soon be a thing of the past, superseded by a pharmacological approach or even genetic editing.

Featured Image: Epigram / Sarah Dalton


For information, advice and support on living with an eating disorder, see the following resources:

Beat - The UK's Eating Disorder Charity / Helpline 0808 801 0677 / Studentline 0808 801 0811

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