Obesity and genes. Which genes cause obesity?

Obesity arises for many reasons, including genetic. Scientists estimate that genes may account for nearly 70% of body weight fluctuations. Does this mean that genes are responsible for the majority of obesity?

Obesity is a complex chronic disease that arises from many environmental, metabolic, psychological, hormonal, and genetic causes. The greatest influence on the development of obesity is exerted by environmental factors, including, above all, the excessive supply of processed high-calorie foods and low physical activity, as well as disturbances in the work of hunger and satiety hormones.

Scientific research shows, however, that genes are also of great importance in the genesis of obesity. We suggest how genes and their inheritance contribute to obesity and what are the types of gene obesity.

Obesity and genes - what are genetic polymorphisms?

Genetic polymorphisms, incl. Single Nucleotide Polymorphisms (SNPs ) are small changes in the genome. The consequence of polymorphisms is the occurrence of various gene variants in the human population. This, in turn, influences the phenotype, which is how each of us looks and responds to environmental factors.

Thus, genetic polymorphisms can affect the risk of developing various diseases, the metabolism of micro- and macronutrients, drugs, and even partially determine the psychological characteristics of a person. Each polymorphism has been given an identification number that begins with the letters "rs" eg rs9939609 for the FTO gene polymorphism .

Obesity and genes - what are genetic mutations?

The mechanism of the formation of polymorphism and genetic mutation is similar, i.e. it results from mistakes made during DNA duplication, but their consequences are different. The biological effect of polymorphism is subtler than that of mutation. Usually it causes a different response to environmental factors, e.g. diet, resistance to toxins. Therefore, it is said that the presence of a specific polymorphism may predispose us to, for example, obesity or breast cancer.

This does not mean, of course, that we have to get sick with these diseases. On the other hand, genetic mutations are usually so harmful to the body that they often lead to serious hereditary diseases. Contrary to polymorphisms, the mutation effect is irreversible and independent of environmental factors. And although this division seems obvious and clear, scientists do not always manage to draw a clear line between a mutation and genetic polymorphism.

Obesity and genes - types of obesity with a genetic basis

• Monogenic (isolated) obesity, i.e. obesity caused by a mutation in a single gene.
• Obesity associated with genetic syndromes , where obesity is only one symptom of an inherited genetic disorder.
• Polygenic obesity (common), i.e. caused by the presence of genetic polymorphisms in several genes - the most common form of obesity with a genetic basis.

Obesity and genes - monogenic obesity

Monogenic obesity occurs in only a few percent of the population and results in grade III obesity, the so-called morbid obesity in early childhood. So far, several genes have been described, the mutations of which can cause monogenic obesity: LEP, LEPR, POMC, MC4R, PCSK1, SIM1, BDNF, NTRK2, GRHB .

These genes code for proteins that may contribute directly or indirectly to obesity. Most of them are related to the so-called the leptin-melanocortin system, which controls the feeling of hunger and satiety.

The LEP ( leptin ) gene coding for leptin and the LEPR (leptin receptor) gene coding for the leptin receptor are the most studied in the context of monogenic obesity . Leptin, or the "satiety hormone", is a molecule secreted by fat cells and regulates the metabolism of food intake. Leptin acts on leptin receptors located in the hypothalamus, through which the hunger reflex is inhibited.

The discovery of the role of mutations in the leptin and its receptor genes in the formation of monogenic obesity was made thanks to observations in laboratory mice in which the LEP and LEPR genes were severely damaged. It was noticed that these mice had an unrestrained appetite, which resulted in extreme obesity. Later studies showed that animals with LEP gene mutations had too low blood leptin levels, and with LEPR gene mutations they were resistant to leptin.

Also in humans, mutations in leptin-related genes result in an almost complete absence of leptin in the blood or resistance of leptin receptors to its effects, and consequently excessive appetite and obesity. Additionally, in humans, the effects of a lack of leptin are behavioral disorders, immunodeficiencies and high blood insulin levels.

Another significant gene whose mutations disrupt the leptin-melanocortin pathway is the MC4R ( melanocortin 4 receptor ) gene encoding the melanocortin 4 receptor. This receptor binds to the proopiomelanocortin hormone, abbreviated POMC .

It is worth mentioning that mutations in the POMC gene encoding proopiomelanocortin also cause monogenic obesity. People with MC4R gene mutations have increased appetite, and the meals they eat are much larger than people without this mutation. In addition, they have high blood insulin levels.

Given that monogenic obesity is caused by genetic mutations that disrupt irreversibly important metabolic pathways, treatment options are limited. The exception is people with a LEP gene mutation , because in this case the leptin deficiency can be supplemented by administering the hormone from the outside.