Genes and obesity

Finding genes involved in obesity helps us understand the complex biological systems that control weight.

The print issue of 'Big Picture on Obesity' discusses the contribution of genes to obesity. The key points are:

only very rarely will a single gene be responsible for obesity
it is likely that hundreds of genes have some influence on body weight
body weight is dependent on both genes and the environment, and on the interaction between the two.

Genes generally act by producing proteins. These proteins, the enzymes, signalling molecules, structural components and so on, are what actually builds a body and makes it work. If a gene influences obesity, it is because it is having some impact on the way the body operates.

And because the human body is so complex, it is not surprising that so many genes and proteins are involved. When we discover that a gene influences weight, it helps us understand the role of its protein product in the body. But we remain a long way from fully understanding how all the different elements work together.

Some examples

A small number of obese children have been found to have mutations affecting the gene coding for leptin. Leptin is produced by adipose tissue and is part of the hormone signalling systems controlling weight. Without leptin, children have a massive appetite.

Mc4R: About 6 per cent of obese children have disruptions in a melanocortin receptor gene, which disrupts its function. The receptor is present in the brain and appears to have a role in balancing energy use and intake. One possibility is that it may affect how much exercise people take.

Some mutations have the opposite effect, causing extreme leanness. These often affect mitochondrial function, leading to inefficient generation of ATP, the cell's energy currency (heat energy is released instead). Theoretically, obesity could be tackled by increasing energy use, rather than decreasing intake or increasing physical activity.

Neuromedin B: Another widely distributed factor, also found in the brain. There are hints that it influences obesity by affecting eating behaviour.

Genes don't act on their own either. The PPARγ2 gene, for example, codes for a protein important in the cell's response to insulin. It is thought to be a potential influence on obesity. But a person's risk will depend on other genetic effects: for example, obesity risk is much higher if someone has a particular form of a second gene, known as ADRβ3.

It's not just changes to a gene that can be important; changes to the way genes are controlled may also be significant. Obesity linked to the interleukin 6 (IL-6) gene, for example, is due to how highly activated the gene is, not to any change in the IL-6 molecule itself.

The picture that is emerging is one of complexity.

Many genes will influence weight and obesity
They act through many different mechanisms
Many effects will depend on small genetic variations that slightly alter a protein's activity; very few will depend on a mutation completely inactivating a protein
Genes interact with each other and with environmental factors.

Genes and obesity

Some examples

Further reading