There are over 1,000 gene variants associated with obesity.³ Each variant has a small effect, but they add up when a person has several of them, predisposing that individual to obesity (polygenic obesity).³  It is rare that someone has a single genetic defect that affects a key hormone within the homeostatic system, causing obesity—only around 5% of people with obesity have this type of “monogenic obesity”.³      

However, genetics does not fully explain the rise in obesity over the past 40 years, a period that is too short for genetic mutations to have evolved across populations, neither does it explain variation across different socioeconomic groups. What has changed is our sociocultural and food environment.⁴ Research has shown that high-fat diets can disrupt both the hedonic and homeostatic systems, highlighting how the biology of our bodies is affected by the environment that we live in.⁵  

When multiple genetic variants combine to make an individual more susceptible to obesity, they can cause metabolic changes that:⁶

Although we cannot change our genes, we can influence the level of “gene expression”—the way your body reads and uses the gene sequence—termed “epigenetics”. For example, eating a high-fat diet can change the function of the finely tuned pathways in the homeostatic system in as little as a week.⁵ However, we can also positively influence gene expression in fat cells, skeletal muscle and the liver through exercise.⁷ So although genetics affect our predisposition to developing obesity, it is not an unavoidable certainty.

Though it is easy to think of obesity as the outcome of an imbalance between energy consumption and expenditure, it is not so simple. Our individual biology, genetics and our environment interact to influence our weight (see Figure 2).⁸

Our basal metabolic rate—the calories that a person’s body needs for basic functions—is determined by our body weight, gender, age and genetics.⁸ This is largely beyond voluntary control. One famous study saw 16 people fed an excess of 1,000 calories per day—by the end of eight weeks some had gained 4kg whilst others only gained 0.5kg, highlighting how differently their bodies responded to the same conditions.⁹  

Weight management is challenging because the body’s systems change in response to our weight. Weight loss is difficult to sustain because the body perceives famine, and its systems compensate in terms of how it uses energy to “protect” us, making it easy to regain weight.⁴ Whereas when we gain weight our metabolic needs increase, so our homeostatic system sends chemical signals telling us to eat more. We then get used to this increase in consumption and so the cycle continues. There is also some evidence that losing weight causes changes to the chemical signals in our body associated with appetite—for example, increases in feelings of hunger that do not return to pre-weight-loss levels even after a year.¹⁰

Figure 2  shows the different influences on our energy expenditure and highlights how daily activity throughout the day has a greater effect than exercise.⁸ Hence, sedentary jobs have a big impact on weight management because they keep us still for long periods when we might otherwise be moving.

Obesity is not just excess body weight—the World Health Organisation (WHO) defines it as a “chronic complex disease defined by excessive adiposity [body fat] that can impair health”, and the World Obesity Federation characterises it as a “chronic relapsing disease process”.^{4, 12} Storing fat is a normal part of a healthy body’s function; issues arise when there is excess body fat. When we have excess fat, the fat cells become enlarged and accumulate around organs, causing inflammation and hormonal imbalances, which contribute to a host of chronic conditions.^{4, 13}

These physiological changes can lead to the body becoming resistant to insulin and the individual developing type 2 diabetes.^{4, 14} In addition, inflammation and high cholesterol in the blood stream contribute to the development of cardiovascular diseases.⁴ Obesity can also result in mechanical issues in the body, such as back pain, osteoarthritis and sleep apnoea.⁷ Figure 3 maps out how some of the physical impacts of obesity can lead to other conditions.⁴

Obesity can directly cause other health conditions, but it also indirectly affects how straightforward those conditions are to manage. In the case of cancer, obesity is a risk factor for developing breast cancer and is associated with a poorer prognosis—the risk of death is more than doubled for women with a BMI of 40 kg/m² or more.¹⁵

We see the complex ways in which our individual biological systems, genetics and environment interact in ways that can be damaging to our health. It is clear that only advising people with obesity to diet and exercise is setting them up to fail. The global rise in obesity looks set to continue unless we make some radical changes.