Background
Obesity is one of the main health issues faced by people of all ages. It affects their lives through limitations implemented on the physical activity, associated disorders, and even emotional pressure. According to the National Institutes of Health (NIH), more than 2 in 3 adults and 1 in 6 children are obese, which means that their body mass index (BMI) is more than 30kg/m2 (“Overweight & Obesity Statistics”). Such results make the professionals presuppose that diabetes will be diagnosed in 1 in 3 children born after 2000. Not only healthcare professionals but also governmental representatives understand that this problem became crucial. Thus, a lot of various initiatives are developed to improve the situation, and large amounts of money are spent.
The issue of obesity requires thorough investigation because enough evidence was gathered to claim that it is the main risk factor for numerous diseases, including cardiovascular, metabolic, osteoarticular ones. For example, it is associated with sleep apnea and diabetes. In addition to that, its connections with cancer and psychiatric illnesses are undeniable. Only in children, obesity causes type 2 diabetes and increases chances of fatal outcomes for coronary heart disease (“Obesity and Overweight”).
The prevalence of obesity and its influences on the public health are widely discussed. However, individual causes and consequences require further investigation. The representatives of the general public tend to believe that obesity is caused by the calorie-rich food and beverages. This fact is also supported by scientists and researchers who investigated the issue. However, more recent studies also emphasize the fact that generic reasons define the way people gain weight and how fat is stored. Thus, even though obesity is often caused by people’s lifestyles, it is tightly linked to genetics due to numerous locations across the genome that affect obesity traits.
Genetic Basis of Obesity
Pathophysiologic mechanisms of obesity are discussed by numerous professionals, but a lot of questions remain unanswered. They are seen as complex interactions of various factors that influence people’s health, including behavioral, environmental, and genetic ones. Today, the issue of obesity becomes more and more critical so that the number of obese individuals among children and adults increase enormously.
Such tendency can be explained by the increased popularity of highly calorific food and beverages that are consumed by human beings and by the dominating sedentary lifestyle that captures people in modern times. It is interesting that a long time ago when food was less available, and humans had to search for it wasting enormous amounts of energy due to physical activity, overweight and obesity could have been treated as a benefit because it had a survival advantage. However, today the situation is much different, and the majority of the general public need to spend more energy than they consume.
Those studies that focused on the issue of obesity and its development provided a lot of evidence that can be used to support the significance of a genetic component in the risk of becoming obese. For instance, twin studies have been used as a model for the evaluation of the genetic component. Their advantage is that they provide an opportunity to compare how monozygotic (MZ) twins and non-identical dizygotic (DZ) twins differ. As the first ones are genetically identical and the next ones share only a half of their genetic material, it was possible to identify how their condition was influenced by genetics.
It was revealed that “the concordance for fat mass among MZ twins has been reported to range from 70–90%, while in DZ twins it is 35–45%” (Xia and Grant 179). These findings prove that obesity has a genetic component that plays a vital role in people’s condition. They emphasize the fact that this disorder can be inherited, which is critical for this issue. However, the way the studies are also performed matters because “in one of Stunkard’s seminal studies, the heritability of 77% for BMI was found to increase to 84% at a 25-year follow-up in a sample of 1,974 MZ and 2,097 DZ male twin pairs” (Xia and Grant 179).
The influence of environmental and genetic factors was also investigated on the basis of adoption and family studies. Their findings revealed that the BMI of adopted children correlated with their biological parents but not with adoptive ones. Considering children separated at birth, it was found out that identical twins who were raised in different environmental conditions still reveal an association between their BMI. Even though there is no such evidence for nonidentical twins raised apart, particular conclusions can be made. In addition to that, researchers identified that various racial/ethnic groups have a particular prevalence of obesity. For instance, in Asian populations, it is about 35% while in Indian populations about 50%. Thus, genetic insight for obesity cannot be denied.
This evidence proves that genetics play a vital role in the determination of BMI, which also presupposes that it affects risks for obesity enormously. However, such findings also provide evidence that supports the complicity of identification of the specific causes of obesity. Interactions between genes and other factors are difficult to explore and are not well-discussed yet (Strander).
Monogenic and Polygenic Obesity
According to the PHG Foundation, genetic differences are tightly associated with those observed within people’s BMI (PHG Foundation 1). In the majority of cases when obesity turns out to be a critical issue during the first years of life, monogenic type of this disorder is observed. It presupposes the presence of a defect only in one particular gene, which makes people eat more so that they get much more energy than those individuals who do not have such issues. This mutation is usually observed in 8 genes and 1 deletion. When this information was revealed, researchers’ understanding of biological mechanisms enhanced enormously. The connection between regulation of energy intake and obesity became undoubtful and was discussed further. Even though such type of mutation is rare individually, all its variants are connected with 1 in 10 cases of severe obesity among children.
Common obesity that is not discussed as an outcome of one mutation, but it is also connected with genes. Unfortunately, regardless of the fact that the association between genetics and this type of disorder is proved, its complex interference is less understood. Such problem can be explained by the implication of multiple genes instead of a single one. They interact with each other, contributing to the adverse outcomes. What is more, they are also influenced by environmental factors that can make the issue of obesity more or less critical. Due to such characteristics, professionals often call this type of obesity a polygenic one. It is stated that “in ‘common’ obesity, genome-wide association studies have identified 32 loci robustly associated with BMI.
However, these 32 loci combined explain less than 1.5% of the total variation in BMI within the population” (PHG Foundation 2). Among these genes, there are some that affect the role of central regulation in obesity through their influence on the central nervous system. Some of them may be affected by monogenic forms of obesity. However, the majority of them are for those markers that cannot be found in the known genes. Thus, a lot of peculiarities remain unknown and require further investigation. For now, it is already known that genetics has an enormous influence on people’s desire to eat. This information can be used to approach the representatives of the general population when developing initiatives for obesity prevention.
The issue of obesity is often investigated nowadays, which means that numerous studies are maintained to discover all its peculiarities. In many cases, researchers focus not only on their sample but also on the condition of their relatives when they search for the reasons and outcomes of obesity. In their findings, they come to a conclusion that at it is a highly heritable trait. That is why it is advantageous to resort to the family history before searching for some health problems when treating patients with obesity.
According to the recent studies, heritability is often associated with this health problem. However, professionals who discuss heritability of illnesses tend to omit it, as they prefer to focus on the problems they believe to be more critical, such as schizophrenia and hypertension. Regardless of the fact that polygenic diseases and other complex traits are usually discussed in this framework, quantitative obesity sub-phenotypes can be considered in order to determine heritability of some characteristics. As a rule, the focus is put on skinfold thickness, waist circumference, and fat distribution.
Familial Obesity
As it was discovered that obesity could be explained by heritability, the sphere of obesity genetics developed. For about 10 years, it was focused on the monogenic or syndromic obesity only. In the laboratory environment, professionals cloned the mouse ob gene and human leptin. The use of human homolog provided an opportunity to develop a paradigm for the area. With the course of time, it was identified that the regulation of appetite that depends on the leptin-melanocortin pathway is connected with a range of different genes and is affected by them enormously.
These variants are aligned with about 5% of morbid obesity cases. Of course, they deal with leptin and its receptor because it affects regulation of appetite. The α-melanocortin-stimulating hormone receptor (MC4R) is discussed in this framework for the same reason. In addition to that, pro-opiomelanocortin (POMC) and prohormone convertase-1 are known for having the influence on this process and developing obesity because of some defects (Nohr et al. 114). These are believed to be pure types of obesity because they are not clinical features of other Mendelian disorders. They presuppose that issues with appetite regulation are caused directly by gene defects and are observed initially without any aligned illnesses.
Testing for Obesity
It is important to continue gathering information regarding the genetic basis of obesity. It can be used to enhance the quality of decision-making regarding genetic testing for the identification of risks and causes of this disorder. Being aware of this critical data, professionals will have an opportunity to implement those initiatives that prevent obesity in the majority of cases or at least improve its treatment. Such decisions should be made on the basis of information obtained due to the testing as well as knowledge, ethical, social, and legal peculiarities.
Trying to predict obesity risk in the framework of common polygenic obesity, professionals focus on 32 genetic loci. However, they are able to explain only about 1.5% of the total BMI variation. In this way, they can hardly lead to concrete conclusions regarding BMI peculiarities and obesity risk because of these limitations. Thus, it is believed that genetic testing is not appropriate for common obesity. Even when using it, researchers fail to come to a proper conclusion. What is more critical, such testing may turn out to be harmful to people because it can reveal some small genetically influenced risk that demotivates individuals to implement those lifestyle changes that have a potentially positive influence on their health condition.
However, if professionals believe that a person is affected by monogenic obesity, genetic testing can be rather advantageous. These forms of obesity are extremely severe, and they lead to the adverse health consequences. They are associated with high levels of physiological and psychological morbidity among the affected populations. Genetic testing provides an opportunity to focus on congenital leptin deficiency. If it is revealed, a monogenic disorder can be diagnosed, and an effective treatment provided timely. Unfortunately, other genetic causes tend to have no appropriate medicament treatment. However, it is still possible to resort to tailored and appropriate management.
Current Approaches to the Treatment of Obesity
The issue of obesity is currently discussed all over the world. In the majority of cases, governments cooperate with healthcare systems in order to develop those guidelines and policies that can be used to prevent and manage obesity. However, it is critical to consider that in the majority of cases they are interested the environmental causes. They are not interested in the role of genetics and tend to mention its role only in a perfunctory manner, pointing out other causes as more severe and complicated ones.
Even though the genomics of obesity is poorly discussed, they are also approached by professionals. Those services that are aligned with them tend to differ between areas. Nevertheless, they are generally focused on the increasing intervention intensity. When treating people with obesity that was observed during the first years of life and associated with hyperphagia, professionals should resort to genetic testing. Within it, they are expected to focus on those genes that are discussed in the framework of monogenic obesity. This testing should be maintained by those professionals who focus on the provision of obesity services. What is more, it should be accompanied by genetic counseling provided before and after this assessment.
Obesity is usually treated on 4 levels that depend on its severity. Level 1 interventions for children and adults resort to population prevention initiatives. These can be school-based programs, parental education, self-help, and national policies. Level 2 interventions are usually used in the framework of community-based programs or primary care, including exercise referral or pharmacotherapy. Level 3 is used in the framework of specialist obesity service with the conduction of genetic testing. Level 4 deals with surgical interventions. While bariatric surgery is offered when dealing with adult population, it is not recommended for children.
Gene Studies
In the majority of cases, those gene studies that discuss common obesity focus on those gene mutations that are found in monogenic forms of this disorder. However, they were able to achieve only partial success considering the determination of those genetic peculiarities that can be used to define obesity. Mainly, it is maintained due to the association with a suspected disease-causing gene. It is often selected on the basis of a biological hypothesis on the pathophysiological mechanisms of obesity. Unfortunately, they are often rather vague and generally still unknown. Thus, the identification of a candidate gene with the help of hypothesis-driven association approach seems to be a tool that is appropriate only for a small fraction of the genetic risk factors (Puiu et al. 274).
Changes in leptin gene and the leptin receptor are discussed when obesity caused by genetic issues is presupposed. There is enough evidence to prove its association with BMI and this disorder in several populations. For instance, professionals pay attention to adiponectin. It is a hormone that enormously affects the regulation of glucose and fatty acids. The findings reveal that it reduces levels of obesity and type 2 diabetes. In addition, its association with these health issues was found in various populations all over the world.
What is more, “association studies of various nominated candidate genes have also implicated the genes encoding such factors as the cannabinoid receptor 1 (CNR1), dopamine receptor 2 (DRD2), serotonin receptor 2C (HTR2C), and SLC6A4, but the most replicated of them is the Pro12Ala substitution in the peroxisome proliferator-activated receptor-gamma(PPARγ) gene, which has been extensively associated with both obesity and type 2 diabetes” (Xia and Grant 184). These research studies prove that obesity is a healthcare issue that is caused not only by severe mutations in a single gene but by rather weak influences of multiple genes. Thus, it is advantageous to consider the usage of non-hypothesis approaches that allow professional to omit basic limitations.
Conclusion
Obesity is a healthcare issue that affects the population of different countries all over the world. Evidence proves that it is associated with numerous leading causes of mortality and morbidity. For instance, diabetes, cardiovascular disease, and even cancers. What is more, it affects economy due to high costs of required services and medications.
It is not only misbalance in energy consumption but a complex mix of biological and environmental factors that affect BMI. In addition to that, obesity is highly heritable, but this characteristic is poorly investigated. Taking into consideration the information discussed earlier, such conclusions related to the link between obesity and genetics can be revealed:
Polygenic obesity: Unfortunately, today common obesity genes cannot be sufficiently identified using genetic testing, which means that there is no necessity to misuse and waste resources recommending them in the hospital settings.
Monogenic obesity: Early-onset obesity that is caused by a single gene mutation can be investigated with the help of genetic testing. However, even in this case, professionals should remember that if a single gene cause was not identified, it does not mean that this option should be totally excluded. There is still a possibility that not all causative genes are already known. However, advantages of genetic testing are still observed. What is more, if the identified type of obesity has no pharmacological treatment, professionals need to consider lifetime support initiatives. They should help patients to lose and manage their weight. Hopefully, additional research studies will improve current knowledge regarding risks and causes of obesity, especially those linked to genetics.
Works Cited
Nohr, Anne et al. “The orphan G protein-coupled receptor GPR139 is activated by the peptides: Adrenocorticotropic hormone (ACTH), α-, and β-melanocyte stimulating hormone (α-MSH, and β-MSH), and the conserved core motif HFRW.” Neurochemistry International, vol. 102, no. 1, pp. 105-113.
“Obesity and Overweight.” WHO, 2016.
“Overweight & Obesity Statistics.” NIH, 2012.
PHG Foundation. Obesity – A Growing Concern.
Puiu, Maria et al. Genetics and Obesity. 2013. Web.
Strander, Sumita. “Genetics to Blame for Obesity.” Dartmouth, 2015.
Xia, Qianghua, and Struan Grant. “The Genetics of Human Obesity.” Annals of the New York Academy of Sciences, vol. 1282, no. 1, pp. 178-190.