Unraveling the Genetics of Obesity: Insights and Implications

Obesity is a complicated health problem that affects millions of people around the world. According to the World Health Organization (WHO), obesity means having too much body fat that could harm your health.

You’re considered obese if your body mass index (BMI), a ratio of your weight to your height, is 30 or more.

Obesity can raise the chances of serious health issues, like type 2 diabetes, heart disease, certain cancers, and osteoarthritis. Therefore, figuring out what causes obesity and its effects is crucial to develop ways to prevent and treat it.

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A major factor that contributes to obesity is genetics. In this article, we’ll dive into how genetics plays a role in obesity, how genetic testing can predict obesity risk, and how using genetics-based therapies and interventions could offer new ways to control obesity.

Quick Overview:

Genetics play a crucial role in obesity, affecting how our bodies process and store energy. Variations in specific genes, like LEP, LEPR, MC4R, FTO, TMEM18, SH2B1, and KCTD15, can predispose individuals to obesity by impacting appetite, metabolism, and fat storage.

These genetic factors, combined with environmental influences like diet and physical activity, contribute to the complexity of obesity.

Twin and family studies indicate that genetics accounts for 40% to 70% of BMI variation, demonstrating the significant role of heredity in obesity.

However, the rapid rise in obesity rates suggests that environmental and lifestyle changes also play critical roles. Genetic testing can identify risk factors and guide personalized interventions, although it’s not definitive in predicting obesity.

Read the full article to understand the multifaceted approach required to deal with obesity, considering both genetic and non-genetic factors.

Making Sense of Genetics and Obesity

Genetics is the study of genes, which are parts of our DNA that carry instructions for making proteins. Proteins are important for how our cells, tissues, and organs work. Genes can interact with each other and with environmental factors to influence physical traits, like height, eye color, and body weight.

Several factors, like variations, epigenetics, and gene-environment interaction, can influence how genes express themselves.

Variations are changes in the DNA sequence that can modify how genes work or control. Some changes can be beneficial, while others can be harmful or neutral.

Epigenetics means changing gene activity without changing the DNA sequence. For instance, chemical tags called methyl groups can attach to DNA and influence how genes are turned on or off.

Gene-environment interaction describes how genes and environmental factors can work together to influence traits. For instance, a person might have a gene variant that makes them hungry all the time, but if they live in a place where food is rare or expensive, they may not become obese.

The role of genetics in obesity can be estimated by a measure called heritability. Heritability is how much of the variation in a trait can be attributed to genetic factors in a given population.

Heritability ranges from 0 to 1, where 0 means that genetics has no effect on the trait and 1 means that genetics fully determines the trait. Heritability can vary based on the population, environment, and method of measurement.

One method to estimate heritability is twin and family studies. Twin studies compare traits between identical twins (who share all their genes) and fraternal twins (who share half their genes).

If identical twins are more alike than fraternal twins for a trait, it suggests that genetics is involved in that trait. Family studies compare traits between relatives who share varying degrees of genetic connection.

For instance, siblings share half of their genes, while cousins share about 12.5% of their genes. If relatives who are closely related are more alike for a trait than those who are less related, it suggests that genetics influences that trait.

Twin and family studies have found that the heritability of BMI is between 40% to 70%, showing that genetics plays a big role in body weight. However, genetics alone can’t explain the rapid increase in obesity rates in recent years. There must be other factors at play in causing obesity.

Key Genes Linked to Obesity

Scientists have found hundreds of genes associated with obesity using various methods, like genome-wide association studies (GWAS), candidate gene studies, and animal models.

These genes can be categorized into two groups: monogenic and polygenic. Monogenic obesity happens when mutations in a single gene have a big effect on body weight. Polygenic obesity is influenced by multiple genes, each having a small effect on body weight.

Monogenic obesity is rare and usually appears in early childhood. It often comes with severe obesity and other symptoms, such as intellectual disability, hormone imbalances, and developmental delays.

Some of the genes involved in monogenic obesity are:

• LEP: This gene carries the instructions for leptin, a hormone that controls appetite and energy usage. Mutations in LEP result in no leptin production, leading to extreme hunger and obesity.
• LEPR: This gene carries the instructions for leptin receptor, a protein that binds to leptin and carries out its signals. Mutations in LEPR result in no leptin response, leading to uncontrollable hunger and obesity.
• MC4R: This gene carries the instructions for melanocortin 4 receptor, a protein that carries out the effects of several hormones on appetite and energy balance. Mutations in MC4R result in the receptor not working, leading to increased food intake and reduced energy usage.

Polygenic obesity is more common and usually appears later in life. It is affected by the combined effects of many genes that interact with environmental and lifestyle factors.

Some of the genes involved in polygenic obesity are:

• FTO: This gene carries the instructions for fat mass and obesity-associated protein, a protein involved in controlling gene expression and energy metabolism. Variants in FTO are associated with increased BMI, body fat, and appetite.
• TMEM18: This gene carries the instructions for transmembrane protein 18, a protein involved in controlling neuronal development and function. Variants in TMEM18 are associated with increased BMI, body fat, and waist circumference.
• SH2B1: This gene carries the instructions for SH2B adaptor protein 1, a protein involved in controlling insulin and leptin signaling. Variants in SH2B1 are associated with increased BMI, body fat, and insulin resistance.
• KCTD15: This gene carries the instructions for potassium channel tetramerization domain containing 15, a protein involved in controlling neuronal differentiation and migration. Variants in KCTD15 are associated with increased BMI, body fat, and waist circumference.

These genes contribute to obesity by affecting various aspects of energy balance, such as appetite, feeling full, energy intake, energy usage, generating heat, fat storage, and fat distribution.

However, these genes do not act alone. They interact with each other and with environmental and lifestyle factors to affect the risk of obesity.

The Interaction between Genetics, Environment, and Lifestyle

Genetics isn’t the only thing that determines obesity. Environmental and lifestyle factors also play a significant role in body weight. These factors can influence how genes express and how genes interact with the environment.

Gene expression is the process where genes are turned on or off to make proteins. Various environmental factors, like diet, stress, toxins, infections, and medications, can affect gene expression.

For instance, a high-fat diet can increase the expression of genes that encourage fat storage and inflammation, while a low-fat diet can increase the expression of genes that encourage fat burning and generating heat.

These changes in gene expression can modify the metabolic pathways and hormonal signals that regulate energy balance.

Gene-environment interaction is when genes and environmental factors interact to influence traits. This interaction can be additive or multiplicative.

For example, if a person has a gene variant that increases their hunger and lives in an environment where food is plentiful and cheap, they may have an added risk of obesity.

There are many examples of gene-environment interaction in obesity.

One example is the interaction between FTO variants and physical activity. FTO variants are linked with increased BMI and body fat, but this link is weakened by physical activity.

In other words, people who have FTO variants but are physically active have a lower risk of obesity than people who have FTO variants but are physically inactive.

Another example is the interaction between MC4R variants and dietary fat intake. MC4R variants are linked with increased BMI and body fat, but this link is changed by dietary fat intake.

In other words, people who have MC4R variants and eat a high-fat diet have a higher risk of obesity than people who have MC4R variants and eat a low-fat diet.

Genetic Testing for Obesity

DNA testing, or genetic testing, is like reading a person’s instruction manual. It can show whether a person has certain genetic markers linked to obesity.

For example, genetic testing can spot if you have variations in genes, like LEP, LEPR, or MC4R, that may cause you to put on weight more easily.

These genes can be a bit like broken switches—they don’t work as they should, and that can make a person very hungry all the time. People who have these “broken switch” genes might need special treatments that help their body manage their weight.

But not all obesity is caused by these “broken switch” genes. Some people have genes, like FTO, TMEM18, SH2B1, or KCTD15, that nudge them toward gaining weight.

These genes are a lot more common, but they don’t have as big an effect on body weight. If you have these genes, it doesn’t mean you’ll definitely become overweight. Things like diet and exercise can still make a big difference.

Having a DNA test to find out about obesity can be a good thing.

• It can help people understand why they struggle with their weight.
• This understanding might inspire them to make healthier lifestyle choices.
• It can also help doctors to suggest the best treatment options.

However, it’s not all positive. Knowing you have a high genetic risk for obesity might make you worried or stressed. Also, there might be a risk of people treating you unfairly if they know about your genetic results.

Therefore, getting a DNA test for obesity should be thought through carefully. It’s important to have a good chat with a healthcare professional before and after the test. They can explain what the test can and can’t tell you about your health.

Future Directions: Genetic-based Interventions and Therapies

Research in genetics is providing new ways to tackle obesity. This includes gene therapy, gene editing, and pharmacogenetics.

Gene therapy is a bit like giving your body’s cells a new set of instructions. Scientists can put a normal or tweaked gene into a person’s cells.

This can help correct a gene that isn’t working properly. For example, in experiments with mice, scientists have used gene therapy to get the body making the hormone leptin again, which helped the mice lose weight.

But it’s not simple. There are many hurdles to overcome before gene therapy can be a common treatment.

Gene editing is another tool where we use a molecular pair of scissors to cut out and change parts of the DNA in a person’s cells.

For instance, scientists have used gene editing to cut down the action of the FTO gene in mice, which helped the mice lose weight. But like gene therapy, gene editing also has many challenges to overcome.

Pharmacogenetics is about tailoring treatments to a person’s unique genetic makeup. It’s a bit like creating a personalized medication plan based on a person’s DNA.

For example, scientists have found that some drugs work better for people with certain genes.

While these treatments based on genetics sound exciting, they are still in the early stages. More research is needed before they can be widely used.

And they bring up ethical questions, like how to make sure they are safe, who can access them, and how to get consent.

So, these treatments will be used along with existing approaches that focus on diet, lifestyle changes and therapies.

Other Causes of Obesity Apart From Genetics

While genetics has a big part in determining if someone will be obese, it’s not the only reason. There are many other factors, apart from genes for obesity, that can make someone overweight.

Here are some of the usual non-genetic reasons that can cause obesity:

Environmental influences

This refers to outside factors that can change a person’s food choices and how active they are. Some examples of environmental factors that can lead to obesity are:

Food surroundings: This includes how easy it is to get food, how much it costs, and how it’s advertised. If high-calorie, fatty, sugary, and salty foods (like fast food, processed food, sweets, and sugary drinks) are everywhere, cheap, and convenient, it can encourage overeating and weight gain.

If healthy foods that are low in calories, fat, sugar, and salt (like fruits, vegetables, whole grains, lean proteins, low-fat dairy, nuts, and seeds) are hard to find, expensive, and inconvenient, it can discourage healthy eating and weight loss.

Physical activity surroundings: This involves how easy it is to find places and chances to exercise.

If there are few or no places to exercise (like parks, trails, gyms, sports facilities, or public transportation), it can discourage people from exercising and losing weight. If there are lots of places and opportunities to exercise, it can encourage people to exercise and lose weight.

Social surroundings: This includes how your family, friends, peers, and the media influence what you eat and how active you are.

If your social environment supports healthy eating and being active (like family meals, cooking classes, fitness clubs, or health campaigns), it can help with weight loss.

If your social environment discourages healthy eating and being active (like peer pressure, teasing, bullying, or unrealistic body images), it can make weight loss harder.

Lifestyle habits

This refers to personal behaviors and habits that can change what you eat and how active you are. Some examples of lifestyle habits that can lead to obesity are:

Diet: This includes what type of food you eat, how much you eat, the quality of your food, how often you eat, and when you eat.

Eating a diet that’s high in calories, fat, sugar, and salt (like fast food, processed food, sweets, and sugary drinks) can cause weight gain.

Eating a diet that’s low in calories, fat, sugar, and salt (like fruits, vegetables, whole grains, lean proteins, low-fat dairy, nuts, and seeds) can help with weight loss.

Exercise: This involves what type of exercise you do, how intense it is, how long you do it, how often you do it, and when you do it.

If you don’t exercise much (like just sitting around or watching TV), you can gain weight. If you do moderate to intense exercise (like walking, jogging, cycling, or swimming), you can lose weight.

Sleep: This includes how much sleep you get and how good that sleep is. If you don’t get much sleep or if your sleep is disturbed (like if you snore, have insomnia, or sleep apnea), you can gain weight.

If you get enough good quality sleep (between seven to nine hours each night), you can lose weight.

Stress: This involves how stressed you are and what’s causing your stress. If you’re really stressed or always stressed (from things like work, family, money, or health problems), you can gain weight.

If you’re only a little stressed or stressed temporarily (from things like temporary or positive events), you can lose weight.

These are some of the common non-genetic factors that can cause obesity, but others may affect a person’s individual situation.

Therefore, it is important to identify and address the non-genetic factors that contribute to obesity as well as the genetic factors.

The Troubles Obesity Can Bring

Obesity can trigger a lot of serious health problems that affect different parts of the body. Some of the major health risks linked to obesity include:

• Heart issues: Obesity can lead to high blood pressure, high cholesterol, and plaque buildup in your arteries. These problems can cause heart diseases, heart attacks, strokes, and heart failure.
• Type 2 diabetes: When you’re obese, your body might not be able to make or use insulin properly. Insulin is a hormone that keeps your blood sugar levels in check. If your blood sugar levels are too high, it can damage your eyes, kidneys, nerves, and blood vessels.
• Cancer: Obesity increases the chances of certain types of cancers, such as breast, colon, uterus, esophagus, pancreas, kidney, and prostate cancer. Obesity can mess with your hormones, cause inflammation, and weaken your immune system, which might be why it can lead to cancer.
• Sleep apnea: When you’re obese, you may have extra fat around your neck and throat. This can block your airways when you’re asleep, leading to snoring, interrupted breathing, low oxygen levels, and poor sleep. Sleep apnea can also raise your risk of heart disease, diabetes, and memory problems.
• Joint pain or osteoarthritis: Obesity puts extra pressure on your joints, especially your knees, hips, and lower back. This extra weight can wear away the cushioning between your bones, causing them to rub against each other. This can cause pain, stiffness, swelling, and difficulties moving around.
• Gallstones: Obesity can make your liver produce more cholesterol. This can lead to the formation of hard deposits, known as gallstones, in your gallbladder. Gallstones can cause belly pain, nausea, vomiting, and infection. Sometimes, gallstones need to be removed through surgery.
• Fatty liver disease: Obesity can lead to too much fat being stored in your liver cells. This can disrupt your liver’s normal functioning and cause inflammation. If not treated, fatty liver disease can lead to severe liver damage or liver failure.

These are just a few examples of the many problems caused by obesity, which can impact both physical and mental health.

That’s why it’s important to prevent or manage obesity as soon as possible.

Ways to Handle Obesity

How we manage or treat obesity depends on many things like how severe the obesity is, whether there are other health issues, and what the person’s goals are.

Here are some of the main strategies for managing or treating obesity:

• Changing your lifestyle: This includes eating healthier and exercising more to burn more calories than you take in. A healthy diet should include a mix of different food groups, like fruits, vegetables, whole grains, lean proteins, low-fat dairy, nuts, and seeds. Try to limit foods that are high in calories, fat, sugar, and salt. Aim for at least 150 minutes of aerobic exercise like walking, jogging, cycling, or swimming each week. You should also do strength training exercises like lifting weights twice a week. These changes can help you lose weight, improve your health, and keep the weight off.
• Medication: Some people might need prescription drugs to help control their appetite, speed up their metabolism, or stop their body from absorbing fat. These are usually for people with a BMI (body mass index) of 30 or more or a BMI of 27 or more, along with other health problems. Medications should be taken alongside lifestyle changes and with the supervision of a doctor. Common obesity medications include orlistat, phentermine, liraglutide, and bupropion-naltrexone. These can help with moderate weight loss but might also have side effects or interact with other medications.
• Surgery: Some people might need surgery to change their digestive system to limit how much food they can eat or how much nutrients they can absorb. Surgery is usually recommended for people with a BMI of 40 or more, or a BMI of 35 or more, along with other health problems. Surgery should be considered a last resort when other weight loss methods fail. Common surgical procedures include gastric bypass, sleeve gastrectomy, gastric banding, and biliopancreatic diversion. Surgery can help with substantial weight loss but can also have risks like infection, bleeding, leakage, malnutrition, or dumping syndrome.

These are some of the ways we can manage or treat obesity, but other methods might be more suitable for different people. The best way to handle obesity is to talk to a doctor or dietitian who can give personalized advice.

Final Thoughts

Obesity is a complicated health problem with many layers to it. It involves both genes for obesity and non-genetic factors, making it a classic case of obesity nature vs nurture.

Obesity genetics or the genetics of obesity play a big part in controlling body weight and how hungry you feel, but they’re not the only things that matter.

Things in our environment and the way we live our lives can also change how our genes work and interact with our surroundings, which can alter the risk of obesity.

While the genetic treatment of obesity can provide a new direction for tackling this health issue, it’s equally crucial to focus on lifestyle changes and environmental factors.

That’s why understanding obesity heredity shouldn’t overshadow the need to address these other important factors contributing to obesity.

References:

• https://www.britannica.com/science/obesity
• https://www.who.int/health-topics/obesity/
• https://obesitymedicine.org/genetic-testing-uncovering-the-underlying-cause-of-severe-obesity/
• https://www.ibdna.com/tests/genetic-predisposition-obesity/
• https://www.nature.com/articles/s41576-021-00414-z
• https://www.mayoclinic.org/diseases-conditions/obesity/symptoms-causes/syc-20375742
• https://www.cdc.gov/vitalsigns/adultobesity/infographic.html
• https://www.verywellhealth.com/obesity-symptoms-4689168