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To diet, or not to diet, that is the question

No matter where you are in the world – everyone’s diet starts tomorrow. Unfortunately, for many of us, tomorrow never comes. From ‘magical’ diet pills to ‘super’ smoothies – the list of diets that will ‘work for you’ are endless.

But why has the world become obsessed with dieting?

Before we can answer this question, we must first look at our environment.

Since 1975, the worldwide prevalence of obesity has nearly tripled – and is projected to continue to rise. Notably, this prevalence has dramatically risen among children. Unfortunately, obesity has reached epidemic proportions globally, with at least 2.8 million people dying each year due to being overweight or obese. As seen with the recent COVID-19 pandemic, being overweight or obese is linked to a range of comorbidities that can be life threatening. With increased opportunities for companies to communicate with consumers, combined with social constructs of the perfect bodyweight – everyone’s attention has been shifted to why the spectrum of body weight is so varied.

In this blog, we delve into the genetics of obesity – from early mouse work to insights from twin studies– as well as the impact society and the environment around us will have in combatting this public health emergency.

The obesity problem

Obesity is a complex trait influenced by a myriad of factors, including genetics, epigenetics and the environment. Although an imperfect measure, body mass index (BMI) defines obesity as any individual between 30 to 39.9 kg/m2, with severely obese people having a BMI over 40 kg/m2. Obesity is considered one of the most preventable causes of death worldwide. It increases an individual’s risk of developing a range of physical and mental conditions, most commonly diabetes.

The cause of obesity is often regarded as a problem of eating too much and moving too little. But as with everything in this life, the problem is not that simple. Now, this is not to deny the fundamental laws of physics. The first law of thermodynamics argues that energy cannot be created or destroyed. This is true for bodyweight. We cannot magic calories away. If we eat fast food every day and don’t do any exercise, then of course we will gain weight. And if we only eat lettuce leaves and run marathons then we will naturally lose weight. The basic energy intake and expenditure concept is just fact.  But the way people behave around food – what drives people to eat more or less – is driven by our biology, more specifically, our genetics.

Regulation of energy homeostasis

I distinctly remember being at university and learning about all the mouse studies undertaken that have shaped our understanding of obesity. What particularly stood out to me were the parabiosis experiments (which now I think about it are really absurd). In these experiments, mice were surgically joined to prove the hypothesis that a circulating factor in the blood suppressed food intake. This subsequently led to the discovery of leptin in 1994. Leptin is a hormone released from fat cells and signals to the hypothalamus in the brain. It helps regulate the energy balance by inhibiting hunger, which in turn diminishes our fat stores. The leptin-melanocortin pathway (Figure 1) is fundamental in the regulation of energy homeostasis. In a simple form, in the fed state circulating hormones such as leptin bind to POMC neurons and produce α-melanocyte stimulating hormone (α-MSH). This then activates the MC4R receptor, which ultimately suppresses appetite.

Figure 1: The leptin melanocortin pathway. (Wallis and Raffan, 2020)

The genetics of it

Obesity is commonly classified into subgroups depending on the suspected aetiology. These include monogenic obesity (extremely severe obesity without developmental delay), syndrome obesity (clinically obese with distinct mental and developmental abnormalities) and polygenic or common obesity (affects the general population with associated health risks).

Monogenic forms

There are several rare genetic forms of obesity that impact critical components of this pathway. Homozygous mutations in the leptin gene result in a severe form of obesity within the first days of life. There are fewer than 100 patients worldwide with congenital leptin deficiency. Affected individuals experience extreme hunger and hyperphagia and without treatment, individuals experience delayed puberty. Fortunately, this disorder can be treated successful with daily subcutaneous injections of human leptin. The discovery of this led many to think the cure for obesity had been found. However, researchers soon began to realise that when leptin is functional, the body does not respond to excess exogenous leptin. Some individuals can also have mutations in the leptin receptor, which does not respond to leptin.

Another key gene involved in monogenic forms of obesity is within the POMC gene. This form is very rare, with fewer than 10 patients worldwide diagnosed. Like the congenital leptin deficiency, POMC deficiency causes severe obesity that begins at an early age. In addition to obesity, affected children often present with red hair and pale skin due to low levels of the adrenocorticotropic hormone. Interestingly, mutations in the canine equivalent have been found in Labradors. Through studying this gene in Labradors, researchers found that with increased copies of the mutation, dogs were on average heavier and more interested in food. They also found that this mutation was more common in assistance dogs. Although these dogs will empty your food cupboards, the mutation makes them more inclined to work for food and thus means they are easily trained.

The most common form of monogenic obesity is caused by mutations within the melanocortin 4 receptor (MC4R) gene, which have been implicated in 1-6% of early-onset severe obesity. While there are no specific treatments for MC4R deficiency, researchers are currently testing an MC4R agonist – setemalontide – in clinical trials.

Syndromic obesity

Syndromic obesity arises from specific genetic defects or chromosomal abnormalities within several genes – either autosomal or X-linked. Over 25 syndromic forms of obesity have been found. One of the most well-known forms of syndromic obesity is Prader-Willi syndrome (PWS). PWS is caused by a chromosomal abnormality within an imprinted region on chromosome 15. It is characterised by early-onset obesity resulting from hyperphagia caused by CNS dysfunction. Syndromic forms of obesity are helping to provide insights into the pathogenesis of disruptions of energy homeostasis.

Polygenic obesity

Epidemiologic studies of common obesity have shown that concordance for obesity decreases in parallel with the degree of relatedness. This indicates that a genetic component is involved in obesity susceptibility. Estimates from early twin studies have indicated that heritability is between 40-70%. While progress in understanding the aetiology of obesity has been largely restricted to monogenic forms, recent technological and analytical advances have enabled the detection of more susceptibility loci. The first substantial advancement in the discovery of obesity susceptibility loci were made in 2007, when the possibility of genome-wide associations studies arose. One of the most well-known findings from these studies is the FTO gene. Polymorphisms within this gene were found to be significantly associated with human body mass. Since then, researchers have identified hundreds of genes of which subtle variations can impact where you sit in the normal distribution of body weight. These genetic variations can have a range of effects from CNS regulation and feeding behaviour (e.g., appetite, satiety, energy expenditure and behaviour) to more peripheral effects such as distribution of weight.

It’s a lot more complex

Of course, it isn’t just genetics that plays a role in obesity and body weight. Ultimately, our entire environment impacts our feeding behaviour which then in turn impacts our body weight. People may question – well our genetics hasn’t changed, so why has obesity risen? The graphic below originally posted in the Washington Post, highlights the upwards trend of weight in the USA from 1984 to 2014. It is true that the reason people have gained weight over the past three decades is due to a change in environment, because people’s genes have not changed. However, if it was all a response to the environment with no biological input than the histogram would shift entirely and would no longer represent a normal distribution. The reason this graph has changed is because we as a population have changed our response to the environment. But how obese we become is ultimately biologically influenced and our genetics plays a huge role in this.  

Histogram plot showing change in BMI from 1984 to 2014. Source: Washington Post.

Obesity is complex. It is a multifactorial disease with social and environmental factors (as well as the biological and genetic factors previously mentioned). One of the most important environmental characteristics is food availability. In the past few decades, we have become increasingly exposed to high fat/caloric and inexpensive foods. Exposure to these foods is inherently linked with socioeconomic status. For example, in areas of poverty, such as Sudan and Ethiopia, where there is lack of food security, individuals die of malnutrition. Whereas, in the West, those from a lower socioeconomic background are at greater risk of obesity due to high caloric foods being cheaper than the more nutritional foods.

Another important factor is transportation. We are living in an age where we can order fast foods straight to our door at the click of a button. Simultaneously, people have access to public transport, taxi services and other transport means – which has altered our physical requirements and resulted in an imbalance in energy intake and expenditure. This has been exacerbated by the pandemic as we have now realised that we can also work and eat from the comfort of our own homes – without stepping a foot outside the door.

Diet starts tomorrow 

In today’s society, I don’t think you can blink without seeing some sort of diet related advice or product. Celebrity culture and social media has created an unrealistic view of the ‘ideal’ body. In fact, social media influencers are often paid by companies to promote diet shakes and lollipops claiming that they have magically helped them lose weight overnight. This has subsequently created toxic connotations relating to the word ‘diet’ and made people fear food. Nonetheless, people diet for many different reasons – from being diagnosed with a condition like diabetes to simply wanting to lose weight.

The question is, does dieting work? Well, theoretically yes. As with the energy balance equation – ultimately if a person eats less calories than they burn, they will lose weight: fact. However, one diet does not fit all and finding the one that works best for you is key.

I think the most important thing to note is that dieting isn’t supposed to be easy. Your body weight is regulated by the brain and when you begin to lose weight the brain naturally reacts to this and tries to intervene by pushing your weight back to what it thinks your normal weight is. Another thing to note, is that it is important to understand how the diet that you select works. For example, some diets that are high in protein, will naturally result in weight loss because protein takes longer to digest which ultimately makes you feel full. Caloric availability is another important consideration. The amount of calories that we actually obtain from food is often not actually the same as what is displayed on packaging. Therefore, blinding counting calories doesn’t make sense. Selecting a diet that suits your biology but also your lifestyle is critical – because a diet will only work if you stick with it.

A societal issue

Maybe I am naïve, but I cannot understand how in 2021 as we speak – as I am typing my words – 12,038… no, 12,042 people have died from hunger today at 9.30am (a number which as I look at my screen is steadily increasing). Simultaneously, the money spent on obesity related diseases just in the USA alone – today – is increasing as quick as milliseconds on a clock. So quick, in fact, that I can’t even get you a figure (but it’s around $236,000,000).

Unfortunately, as we bring people from areas of poverty and starvation – we will begin to expose them to the environment of the West – which is where we will likely see the true burden of this condition. We can hopefully fix this before it gets to that state. But how?

We can’t change our genetics (well, we can’t yet). But we can change our environment.

Growing up with a single parent mum, I know first-hand how choices can be restricted by your socioeconomic class. From picking the cheaper, more caloric food option, to having limited time to prepare fresh meals. Time and time again we see adverts saying ‘eat well for less’. But for many, it’s not that simple. And when we turn to our governments to help with this – the ignorance is deafening. Last year (2020) in the UK, England footballer – Marcus Rashford – had to campaign for access to healthy free school meals for underprivileged families during lockdown. Rashford empathised with families, having struggled with food poverty when he was younger. But this begs the question – if our own government cannot understand the burden of food poverty – who else are we supposed to turn to?

Obesity and food insecurity are societal issues. People are often quick to blame and judge others – arguing “well just stop eating” and “well don’t have kids if you can’t afford to feed them”. However, it is clear that before we can feed the nation the right food, we must first feed the right information to those who are misinformed.

“In order to really solve obesity, we need to make the healthier choice, the cheaper more convenient choice.” – Giles Yeo

Check out our interview with Giles Yeo, where he delves into the genetics of obesity, the impact of our diet on our gut health and why our food environment plays such a big role in our health.


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  • Lee A, Cardel M, Donahoo WT. Social and environmental factors influencing obesity. Endotext [Internet]. 2019 Oct 12.
  • Yeo G. Is Obesity a Choice? The Royal Institution. 2019. Available:

More on these topics

Epigenetics / Genetics / Microbiome / Obesity

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