これまでの研究で、肥満に関連する複数の遺伝子が特定されています。例えば、β3アドレナリン受容体遺伝子（ADRB3）は、基礎代謝やエネルギー消費に関与し、その変異が肥満のリスクを高めることが示されています。 また、UCP1遺伝子（uncoupling protein 1）は、脂肪組織の熱産生に関与し、その変異が脂質代謝の低下と関連しています。
Obesity and metabolism are factors that are deeply related to our health and quality of life. In recent years, advances in genetic testing have made it possible to understand an individual’s obesity risk and metabolic characteristics from a genetic perspective. In this article, we will explain in detail the differences between obesity and metabolism that can be revealed through genetic testing, using the latest research and concrete examples.
1. Obesity and genetic factors
Obesity is a condition caused by the accumulation of excess fat and is largely influenced by genetic factors as well as lifestyle and environmental factors. Research has shown that genetic factors account for about 25% of obesity overall. By understanding these genetic factors, it is hoped that preventive measures and treatments appropriate for each individual can be developed.
1.1 Identification of obesity-related genes
Previous studies have identified several genes related to obesity. For example, the β3 adrenergic receptor gene (ADRB3) is involved in basal metabolism and energy consumption, and its mutations have been shown to increase the risk of obesity. citeturn0search1In addition, the UCP1 gene (uncoupling protein 1) is involved in thermogenesis in adipose tissue, and its mutations are associated with reduced lipid metabolism. citeturn0search15
1.2 Genetic polymorphisms and obesity risk
Genetic polymorphisms, especially single nucleotide polymorphisms (SNPs), are known to affect an individual’s risk of obesity. For example, a specific SNP in the FTO gene is associated with a preference for high-calorie, high-fat foods and a tendency to overeat, which increases the risk of obesity. Detection of these genetic polymorphisms is being used to prevent and treat obesity as part of personalized medicine.
2. Metabolic and genetic factors
Metabolism refers to the set of chemical reactions involved in the production of energy and the utilization of nutrients in the body. Genetic factors influence these metabolic processes and determine an individual’s energy expenditure and efficiency in metabolizing nutrients.
2.1 Basal metabolic rate and genes
Basal metabolic rate (BMR) is the amount of energy consumed at rest and varies from person to person. Genetic testing can help understand an individual’s metabolic characteristics by identifying mutations in genes involved in basal metabolism.
2.2 Energy metabolism-related genes
Analysis of genes involved in energy metabolism can clarify an individual’s metabolic tendencies for carbohydrates, lipids, and proteins, and can help develop appropriate nutritional management and diet strategies.
3. The reality and use of genetic testing
Genetic testing involves taking oral mucosa or blood samples and analyzing specific gene polymorphisms, which can help assess an individual’s obesity risk and metabolic characteristics and enable personalized health management.
3.1 Example of obesity genetic testing
For example, one clinic is analyzing five genes (FTO gene, ADRB3, UCP1, ADRB2) from oral mucosa to assess an individual’s risk of obesity and metabolic characteristics. citeturn0search15 Based on the results of such tests, appropriate diet plans and lifestyle modification measures are proposed.
3.2 Use of genetic testing kits
In recent years, it has become possible to easily analyze obesity-related genes at home using commercially available genetic testing kits. This allows people to receive advice on diet and exercise that is tailored to their individual constitution.
4. Limitations and precautions of genetic testing
Genetic testing is a useful tool for assessing an individual’s obesity risk and metabolic characteristics, but it also has some limitations and precautions.
4.1 Accuracy of genetic tests and challenges in interpretation
Genetic testing can identify gene polymorphisms involved in obesity and metabolism, but how to interpret the results and apply them to real life is important. For example, even if a particular SNP is said to be associated with obesity, the magnitude of its effect varies from person to person. Not everyone who has a certain gene polymorphism will become obese, and conversely, even people who do not have that gene can become obese. This is because genes and environmental factors interact with each other to control weight and metabolism.
In addition, the same genetic polymorphism may have different effects in different populations. For example, it has been reported that genetic polymorphisms that are strongly associated with obesity in Westerners have a smaller effect in Japanese people. Therefore, rather than simply applying the results of genetic testing, it is necessary to use them after taking into account the individual’s lifestyle and cultural background.
Furthermore, although the accuracy of genetic testing has improved with technological advances, it does not cover all genetic factors. The currently identified obesity-related genes are only a partial list, and new genes may be discovered in future research. Therefore, rather than determining future obesity risk based solely on current test results, interpretation based on ongoing research progress is required.
5. Epigenetic effects related to obesity and metabolism
In recent years, the influence of epigenetics has been attracting attention in research on obesity and metabolism. Epigenetics refers to the mechanism that controls gene expression without changing the base sequence of DNA.
5.1 DNA methylation and obesity
DNA methylation is one of the important epigenetic modifications that suppress gene expression. Studies comparing obese and non-obese individuals have reported significant differences in DNA methylation patterns in specific gene regions. For example, a high DNA methylation level of the FTO gene is associated with increased fat accumulation.
It has also been shown that DNA methylation patterns change depending on lifestyle. For example, it has been shown that continuing a healthy diet and exercise can change the methylation of obesity-related genes and promote fat burning. This suggests that environmental factors, rather than just genetic influences, affect gene expression.
5.2 Histone modifications and metabolic regulation
Histone modification is a mechanism that regulates gene expression by chemically modifying the histone proteins around which DNA is wrapped. It has been reported that histone modification patterns differ in individuals with obesity or metabolic disorders, and it is known that this affects the expression of energy metabolism-related genes, particularly in adipose tissue and liver.
For example, it has been suggested that children born to mothers exposed to starvation have altered histone modifications in metabolic genes, leading to increased energy efficiency throughout their lives. This is important evidence that genetically determined obesity and metabolic traits can actually be altered by acquired environmental factors.
In this way, epigenetics plays a role in adjusting gene expression levels and varying the risk of obesity and metabolic disorders. The combination of genetic testing and epigenetics is expected to make more detailed personalized medicine possible.
6. Microbiome and obesity/metabolism
Recent research has revealed that the intestinal bacteria (microbiome) have a significant impact on our weight and metabolism. The types and balance of intestinal bacteria, interacting with an individual’s genetic background, affect energy absorption and fat accumulation.
6.1 Gut bacterial composition and obesity
Intestinal bacteria are broadly divided into two groups: Bacteroidetes and Firmicutes . Studies comparing obese and non-obese people have shown that obese people tend to have a higher proportion of bacteria in the Firmicutes phylum and a lower proportion of Bacteroidetes. It is believed that a high ratio of this bacteria increases energy absorption from food and makes it easier for body fat to accumulate.
It is also known that certain intestinal bacteria improve fat burning and insulin sensitivity. For example, the bacterium Akkermansia muciniphila is believed to strengthen the intestinal barrier function and may contribute to the prevention of obesity and diabetes. For this reason, improving the intestinal environment may be an effective measure for people who are genetically at high risk of obesity.
6.2 Interaction between gut bacteria and epigenetics
Gut bacteria are known to produce short-chain fatty acids (SCFAs) and regulate gene expression through epigenetics. For example, butyrate produced by gut bacteria can inhibit histone deacetylases (HDACs) and alter the expression of metabolism-related genes.
In this way, the interaction between genes and gut bacteria is an important factor in determining individual metabolic characteristics. In the future, it is expected that more precise personalized medicine will be possible by combining genetic testing with gut bacteria testing.
We are entering an era where genetic testing can help us gain a deeper understanding of our physical constitution and metabolic characteristics and enable us to manage our health based on that understanding.
7. The relationship between genes and hormones that affect obesity and metabolism
Genes not only have a direct effect on obesity and metabolism but also play a major role in the hormone balance in the body. Hormones control energy consumption, appetite, fat accumulation, and other factors, and it is known that their functions differ depending on genetic factors.
7.1 Leptin and genetic factors
Leptin is a hormone secreted from fat cells that acts on the hypothalamus in the brain to suppress appetite. It is known that when there is a mutation in the leptin receptor (LEPR) gene, leptin signaling does not function properly, making it difficult to suppress appetite. People with this gene mutation are less likely to feel full, making them more likely to overeat and increasing their risk of obesity.
There is also a phenomenon called leptin resistance, in which the hypothalamus does not respond appropriately in obese people, even when leptin levels are high. This is related to genetic as well as dietary and environmental factors, and can be improved with an appropriate diet and exercise.
7.2 Ghrelin and genetic factors
Ghrelin is a hormone secreted from the stomach that stimulates appetite. It has been suggested that certain polymorphisms in the GHRL gene affect the amount of ghrelin secreted and the sensitivity of the receptor and thus play a role in regulating appetite.
High levels of ghrelin secretion increase appetite and food intake. In particular, if there is a mutation in the GHRL gene, ghrelin secretion may be higher than normal, which may increase the tendency to overeat. On the other hand, low levels of ghrelin secretion suppress appetite and reduce food intake, so it is known that people naturally tend to choose low-calorie meals.
7.3 Insulin sensitivity and genetic factors
Insulin is a hormone that regulates blood sugar levels and plays an important role in metabolism. When the function of insulin is reduced due to genetic mutations, sugar metabolism is not carried out properly, and fat accumulation is likely to progress.
For example, the TCF7L2 gene is involved in insulin secretion and glucose metabolism, and it is known that people with certain gene polymorphisms have reduced insulin sensitivity and an increased risk of type 2 diabetes. People with this gene should be careful about their carbohydrate intake and maintain a diet that is conscious of controlling blood sugar levels.
8. Personalized diet strategies using genetic testing
By understanding your tendency towards obesity and metabolism through genetic testing, you can find the best diet method for you. By knowing which nutrients you can metabolize efficiently and what kind of exercise is effective for you, you can manage your weight efficiently.
8.1 Low-Carb vs. Low-Fat Diets
Genetic testing can distinguish between people with high and low carbohydrate metabolism. For example, people with many copies of the AMY1 gene (amylase gene) tend to be less likely to gain weight even on a high-carbohydrate diet because they digest and absorb carbohydrates more efficiently. On the other hand, people with fewer copies of AMY1 tend to store excess carbohydrates as body fat, so a low-carbohydrate diet may be more suitable for them.
In addition, people with PPARG gene polymorphisms are more likely to have a reduced metabolism of fat, so a low-fat diet is considered effective. As such, the optimal diet method differs depending on genetic differences, so it is important to provide dietary advice tailored to each individual’s constitution.
8.2 Cardio vs. Strength Training
The effect of exercise also depends on genetic factors. The ACTN3 gene is involved in the development of fast-twitch muscle fibers (muscles that generate explosive power), and mutations in this gene result in different muscle types.
People with the “RR” type of ACTN3 gene are more likely to develop fast-twitch muscle fibers, so high-intensity exercise such as sprinting and weight training are suitable for them.
“RX type” people have a balance of fast-twitch and slow-twitch muscles, and both endurance and explosive exercises are effective for them.
People with “XX type” tend to have fewer fast-twitch muscle fibers and are suited to endurance exercise (such as jogging and swimming).
In this way, by utilizing genetic testing, you can choose the exercise method that suits you best and train efficiently.
8.3 Appetite control and genetic factors
It is important for people who are susceptible to obesity-related genes to know how to properly control their appetite. People who are genetically predisposed to have a strong appetite will need to devise ways to time their meals and increase satiety.
Eat a high protein diet (to improve leptin resistance)
Chew your food thoroughly (suppresses the secretion of ghrelin)
Eat meals at regular intervals (to prevent blood sugar spikes)
By utilizing genetic testing, it is possible to manage your diet based on more scientific evidence, allowing you to maintain a healthy body shape without any strain.
In this way, by utilizing genetic information, we can understand differences in obesity and metabolism and effectively manage our health in ways that are tailored to us.
9. The relationship between genes and stress: Effects on obesity and metabolism
Stress is one of the factors that greatly affect obesity and metabolism, and it is known that responses to stress differ depending on genetic factors. The secretion of the stress hormone cortisol and the body’s response to it vary from person to person, and these differences are determined by genes.
9.1 Genetic associations between cortisol and obesity
Cortisol is a hormone secreted by the adrenal gland and plays a role in responding to stress. However, it is known that exposure to chronic stress leads to excessive secretion of cortisol, which promotes the accumulation of body fat. In particular, the NR3C1 gene (glucocorticoid receptor gene) is one of the important genes that determine sensitivity to cortisol.
Mutations in the NR3C1 gene make people more susceptible to the effects of cortisol and more likely to increase appetite during times of stress. People with this type of gene are more likely to consume sweet and high-calorie foods when they feel stressed, which increases their risk of obesity. Conversely, people with certain variants of this gene are known to have a lower risk of overeating because they are more resistant to stress and less susceptible to the effects of cortisol.
9.2 The relationship between stress and appetite hormones
When we feel stressed, the balance of hormones that control our appetite also changes. In particular, neurotransmitters such as serotonin (5-HT) and dopamine play an important role in stabilizing our appetite and mood.
HTR2A gene (serotonin receptor gene): Serotonin is a hormone that gives you a feeling of fullness, and it has been found that mutations in the HTR2A gene reduce the function of serotonin and increase appetite. This increases your tendency to prefer high-carbohydrate meals and increases your risk of weight gain.
DRD2 gene (dopamine receptor gene): Dopamine is also known as the “pleasure hormone” and is responsible for the food reward system. People with a mutation in this gene are known to feel a stronger sense of satisfaction when they consume a high-fat, high-sugar meal, and are prone to overeating.
These genetic differences affect eating behavior during stress, so it is important to understand your own genetic risk and live a life that focuses on stress management.
10. Latest trends in obesity and metabolic management using genetic testing
Genetic testing technology is evolving every day, and in addition to conventional genetic testing, new methods that allow for more precise analysis are emerging. Here we will introduce the latest trends.
10.1 Detailed analysis by next generation sequencing (NGS)
Conventional genetic testing typically involves analyzing specific SNPs (single nucleotide polymorphisms), but the use of next-generation sequencing (NGS) technology has made it possible to analyze genetic information in more detail.
By utilizing NGS, it is possible to analyze the overall genetic variation related to obesity and metabolism, enabling more accurate risk assessment. For example, by taking into account the interactions of multiple genes, it is now possible to more accurately predict the risk of obesity and metabolic disorders that could not be explained by a single gene mutation alone.
10.2 Personalized diet plan using AI
Advances in genetic analysis using artificial intelligence (AI) have made it possible to create personalized diet plans. Systems are being developed that can propose the most effective diet and exercise plans by integrating the analysis of not only genetic data, but also intestinal bacteria data, lifestyle data, hormone levels, and more.
For example, some companies are developing services that provide customized meal menus by analyzing each individual’s metabolic characteristics and nutrient absorption capacity based on the results of genetic testing. This makes it possible to create a “diet that is optimized for the individual” rather than a “one-size-fits-all diet.”
10.3 Gene editing technology and future obesity treatment
With the development of gene editing technologies such as CRISPR-Cas9, it may be possible to modify obesity-related genes in the future. At present, due to ethical and safety issues, application to humans is limited, but in animal models, fat accumulation has been successfully suppressed by modifying obesity-related genes.
In the future, if gene editing technology can be applied more safely, preventive gene therapy may be possible for people who are genetically at high risk of obesity. However, ethical issues must be overcome, and careful discussion is required.
11. Future outlook for genetic testing
Genetic testing is expected to continue to evolve as an important tool in personalized medicine for obesity and metabolism. Current testing is primarily focused on prediction and diagnosis, but in the future, it is expected to be used as a guide for treatment and intervention.
Furthermore, combining genetic information with real-time health data will enable more precise health management. For example, by integrating wearable devices with genetic data , technology is being developed that can analyze real-time blood sugar fluctuations and metabolic data to suggest optimal meal and exercise timings.
In this way, genetic testing is no longer simply a diagnostic tool; it has the potential to play a central role in future health management.
Summary
We are entering an era where genetic testing can scientifically analyze individual differences in obesity and metabolism and identify optimal diet and exercise methods. It has been found that the FTO gene and PPARG gene are involved in obesity risk, and genetic mutations in leptin and ghrelin affect appetite. In addition, epigenetics and interactions with intestinal bacteria are also factors in obesity. With the evolution of AI and next-generation sequencing technology, more precise personalized medicine is possible, and in the future, obesity treatment by gene editing is expected.
