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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?

Obesityis a complex chronic disease that arises from many environmental, metabolic, psychological, hormonal and genetic causes. Environmental factors have the greatest impact on the development of obesity, 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 (SNPsSingle Nucleotide Polymorphisms ) are small changes in the genome. The consequence of polymorphisms is the occurrence of various gene variants in the human population. This, in turn, affects the phenotype, i.e. how each of us looks and responds to environmental factors.

Thus, genetic polymorphisms may 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", e.g. rs9939609 for theFTOgene polymorphism.

Obesity and genes - what are genetic mutations?

The mechanism of the formation of polymorphism and genetic mutation is similar, ie 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. That is why 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. Unlike polymorphisms, the mutation effect is irreversible andindependent 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.

Check what are the causes of obesity and how it is safely treated!

Obesity and genes - types of obesity with a genetic basis

  • Monogenic obesity(isolated), i.e. one 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 genetic obesity.

"Obesity genes" may predispose not only to obesity itself. Few genes encode proteins responsible for only one biochemical pathway, so the effects of one gene polymorphism may be multidirectional. Therefore, "obesity genes" may also predispose to type 2 diabetes, lipid disorders, cancer and cardiovascular diseases.

Obesity and genes - monogenic obesity

Monogenic obesity occurs in only a few percent of the population and results in the third degree of 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 encode 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 best researched in the context of monogenic obesity are: geneLEP(Englishleptin ) encoding leptin and geneLEPR(leptin receptor) encoding the receptor for leptin. 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 the mutation of leptin genes and its receptor in the formation of monogenic obesity was due to observations on laboratory mice in which theLEPandLEPRgenes they were badly damaged. It was noticed that these mice had an unrestrained appetite, which resulted in extreme obesity. Later studies showed that animals with theLEPgene mutations had too low leptin levels in the blood, and those with the gene mutations LEPRwere leptin resistant.

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

Another significant gene whose mutations disrupt the leptin-melanocortin pathway is theMC4Rgene ( melanocortin 4 receptor ) encoding the melanocortin 4 receptor This receptor binds to the hormone proopiomelanocortin, abbreviatedPOMC .

It is worth mentioning that mutations in thePOMCgene encoding proopiomelanocortin also cause monogenic obesity. People with theMC4Rgene mutations have increased appetite, and the meals they eat are much larger than those 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 are people with theLEPgene mutation, because in this case the leptin deficiency can be supplemented by administering the hormone from the outside.

Obesity and genes - obesity associated with genetic syndromes

Obesity-related genetic syndromes are a group of diseases in which obesity is only one symptom. In total, about 25 such disease entities have been described. In addition to obesity, they are characterized by birth defects, intellectual disabilities and specific behavioral disorders.

The genetic syndromes associated with obesity are extremely rare and are mainly caused by extensive genetic alterations in the loss or duplication of chromosome fragments. Chromosomes are the structures on which all genes in a cell reside, and therefore their damage results in abnormalities in many genes at once.

The most common is Prader-Willi syndrome. The incidence of this syndrome is 1: 10,000-50,000 births. The main cause of PWS is the loss of a fragment of chromosome 15 (region 15q11-q13) that is inherited from the father. Such large genetic losses cause many genes to malfunction. Therefore, in addition to extreme obesity, people with PWS suffer from:

  • decreased muscle tone (hypotonia),
  • weak facial expressions,
  • excessive appetite,
  • intellectual disability, sleep disorders.

LikelyThe mechanism behind obesity in this syndrome is a disruption of the biochemical pathways in the hypothalamus related to the secretion of ghrelin (called the "hunger hormone"). High levels of ghrelin in patients result in uninhibited appetite.

Another example of a genetic syndrome in which obesity is the dominant symptom is Bardet-Biedl syndrome. In patients with this syndrome, obesity develops between the ages of 1 and 2. Other symptoms of the syndrome include:

  • presence of extra fingers and toes (polydactyly),
  • degeneration of the retina of the eye,
  • intellectual disability,
  • developmental disorders of the genital organs and kidneys.

The syndrome is caused by mutations in at least 20 genes (includingBBS1, BBS2, BBS3, BBS4, BBS5, BBS6, BBS7, BBS8, BBS9, BBS10 ).

Other genetic syndromes related to obesity described include:

  • Cohen's band
  • Börjeson-Lehman team
  • Alström's team
  • Simpson-Golabi syndrome
  • Carpenter's team
  • Wilson-Turner syndrome
  • Smith and Magenis team
  • chromosome 14 disomy syndrome

Obesity and genes - polygenic obesity

The discovery of polygenic obesity was groundbreaking as it is believed that it may account for more than 90% of obesity. In very large studies involving identical twins (i.e. with the same genome), it has been proven that genes account for almost 70% of the difference in body mass measured by the body mass index (BMI).

However, it is nevertheless emphasized that in polygenic obesity, the interaction between "obesity genes" and environmental factors, i.e. lifestyle, is very important. Therefore, in this case we are talking about a predisposition to obesity.

In other words, just because we have unfavorable variants of the "obesity genes" does not mean that we have to become obese. For this reason, research into polygenic obesity is very difficult, as it is not easy to prove a cause-and-effect relationship between specific genes and lifestyle.

Important

Very often, changes in genes contributing to monogenic obesity may be involved in the formation of polygenic obesity. An example is genMC4R . The difference is that in the case of polygenic obesity, the degree of gene damage is milder as it is caused by polymorphism.

It is believed that the mechanism by which polymorphisms of theMC4Rgene influence the predisposition to obesity is due to frequent snacking between meals and the tendency to overeat. Risk variants of the rs17782313 polymorphism of the geneMC4R(CT and CC variants) were associated withhigher BMI in both children and adults, more frequent snacking and a tendency to eat high-calorie foods.

Interestingly, it has been shown that the Mediterranean diet can weaken the impact of unfavorable variants of both theFTOandMC4R .

gene polymorphisms

The first discovered and the best-studied gene predisposing to obesity is theFTOgenefat mass- and obesity-associated gene. It encodes the enzyme 2-oxoglutarate demethylase, which is expressed especially in the hypothalamus and pancreatic islets, which indicates its important role in the regulation of energy metabolism in the body.

The presence of an unfavorable variant of the rs9939609 polymorphism of the geneFTO(the so-called AA variant, which occurs in 16% of Europeans) has been associated with a higher risk of obesity and type 2 diabetes compared to typical variants of this gene (the so-called TT and TA variants).

Although the molecular mechanisms leading to such predispositions have not been fully elucidated, it has been proven in studies involving children that the polymorphisms of theFTOgene may influence, among others, on the supply of food, especially the one with high calories. It was proven that children with the unfavorableFTOgene variant who had unlimited access to high-calorie food consumed significantly more of it than children with the typical variants.

However, the most interesting from the point of view of polygenic obesity treatment strategies is the "sensitivity" of theFTOgene polymorphisms to lifestyle changes. Published meta-analyzes showed that obese people with variant AA, in addition to being more susceptible to adverse lifestyle effects and thus predisposed to obesity, can more effectively reduce weight by introducing an appropriate diet and physical activity than people with variants of TT and TA.

In other studies, it has been shown that in people undergoing bariatric surgery, theFTOgene variation can also help maintain a he althy body weight after surgery.

Read also: Obesity and genes. What is Bardet-Biedl syndrome?

Do you know that…

We can change our genes with our lifestyle.As absurd as it sounds, the discoveries made in recent years show that it is! Responsible for this are the so-called epigenetic modifications, which are a kind of link between genetics and the environment. Epigenetic modifications can literally "turn on" and "off" the expression of certain genes via molecular chemical tags.

Most importantly, these types of changes do not change the structure of DNA, so they are not a type of mutationgenetic that is irreversible, but something that changes dynamically, especially under the influence of environmental factors. It is epigenetic modifications that can be triggered by lifestyle, thus changing the risk of obesity and its complications.

Obesity and genes - what is responsible for obesity: genes or the environment?

The answer to this question is difficult. In the case of monogenic obesity and obesity-related genetic syndromes, environmental factors will not influence the obesity phenotype as strongly (if at all) as in the case of polygenic obesity, the phenotype of which closely depends on interaction with the environment.

Particularly important in the development of obesity areeating habits , which are largely shaped by the environment in which we grow up. Scientific research shows that the role of parents and the eating habits passed on by them are very important here. It is emphasized that this especially applies to eating less caloric foods, but more nutritious, such as vegetables, the consumption of which is shaped by positive or negative experiences with these foods. Contrary to high-calorie foods, e.g. sweets, where innate predispositions play a greater role.

Do you know that…

Eating habits can be influenced by genes, for example through the sense of taste. Recently, the so-called a fat flavor which may represent a sixth type of flavor recognizing fatty acids. The taste sensations associated with products rich in fat may lead to its excessive supply in the diet and, consequently, obesity. The "taste of fat" may be influenced by the polymorphisms of the geneCD36(Englishcluster of differentiation 36 ).

There are three most common polymorphisms of the geneCD36 :

  1. rs1761667
  2. rs1527483
  3. rs3840546

It has been shown that people with the GG and GA variants of the rs1761667 polymorphism are more sensitive to the "taste of fat" and have the ability to sense a significantly lower concentration of fatty acids in food than the AA variants, which need to achieve the same level of taste sensation. much higher content of this ingredient in dishes.

"The taste of fat" may indirectly affect eating habits. Hypersensitivity to fatty acids in food is associated with a lower supply of high-fat products in the diet and a lower BMI index.

Research has shown that alsoleisure activities , for example, watching TV can amplify the negative effect of "obesity genes". Of course, this does not suggest that the genes interact with the time spent beforeTV, but the relationship between the way of spending time (in this case not very active) and the increased risk of obesity. Other studies have shown that people who prefer this form of spending their free time also consume more high-calorie, unhe althy food.

Most specialists emphasize that, after all, it is environmental factors that play a key role in the obesity epidemic. Explaining this above all by the fact that our genes do not change as quickly as the lifestyle we currently lead. An example are the previously mentioned polymorphisms of theFTOgene, where many studies have shown that the predisposition to obesity can be overcome with appropriate diet and physical activity.

Obesity and genes - molecular diagnostics of obesity

Molecular research into the genetic basis of obesity can be performed at any age, as our genome is unchanged throughout our lives. Important in deciding to perform the test is a detailed family history, which may suggest hereditary nature of obesity.

If, in addition to obesity, the patient has other serious disorders, such as intellectual disability, this may suggest a genetic syndrome related to obesity. In the diagnosis of obesity-related genetic syndromes, cytogenetic techniques are used to assess the structure and number of chromosomes in a cell.

When testing excludes genetic syndromes, an interview regarding nutrition and habits is also important. If it indicates an excessive caloric intake with low physical activity, then polygenic obesity should be considered. In this case, you can test for genetic polymorphisms, e.g. genesFTOorMC4R , which can confirm the predisposition to obesity.

The tests for the presence of mutations and polymorphisms are performed using molecular biology methods, mainly based on the polymerase chain reaction (PCR). The most common is Sanger sequencing. Tests can be performed in specialized hospitals with genetic laboratories.

In addition, there are several commercial companies on the market that carry out genetic testing for "obesity genes". The obtained result should be consulted with a specialist in medical genetics in order to assess the clinical significance of the detected genetic mutation / polymorphism.

Important

Poradnikzdrowie.pl supports safe treatment and a dignified life of people suffering from obesity. This article does not contain discriminatory and stigmatizing content of people suffering from obesity.

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Obesity