Is Obesity Genetic? Understanding the Impact of Genetics on Weight

In weight gain, we often think about food and exercise. But there's more to the story. Genetics, our unique DNA, plays a role too.

While what we eat and how active we are matter, recent studies suggest that our genes also contribute. Like genes influence our height, they can affect up to 80% of our body weight differences.

In this article, you’ll learn how genes can contribute to obesity. We'll also look into testing and treatment options.

Understanding Obesity

Obesity is a complex and multifactorial medical condition characterized by an excessive accumulation of body fat.

It is typically assessed using the body mass index (BMI), calculated by dividing a person's weight in kilograms by the square of their height in meters.
A BMI of 30 kg/m² or higher indicates obesity in adults. Obesity significantly increases the risk of various health issues, including diabetes, heart disease, stroke, and certain cancers.

But how is obesity impacting people worldwide?

Global Obesity Problem

Obesity is a global health concern affecting people of all ages, from children to adults. The prevalence of obesity has been steadily rising, leading to an epidemic that poses significant challenges to public health systems worldwide.

The World Health Organization (WHO) reports that nearly 39 million children under five are overweight or obese. In the US, obesity affects approximately one in three adults, with childhood obesity prevalence at 19.3% based on data from 2017-2018.

Projections indicate that if the current trend continues, by 2030, obesity rates could increase to about 20% of the world's population falling into the obese category. This alarming trend underscores the urgency of understanding the underlying factors contributing to obesity, including genetic and environmental influences.

Genes and Health

Genes are segments of DNA (deoxyribonucleic acid) that carry instructions for building and maintaining the structures and functions of the cells in our bodies. They serve as the basic units of heredity and are passed from parents to their offspring.

Genes determine traits and characteristics like eye color, height, and susceptibility to certain diseases.

But how do these genes actually lead to diseases that seem to run in families?

It’s called mutations in genes that can cause diseases ranging from minor impacts to severe conditions. Many common diseases result from mutations, lifestyle choices, and environmental factors. Even genetically similar individuals can experience diverse health outcomes due to their decisions and surroundings.

Genetic Basis of Obesity

In the context of genetic obesity, it becomes apparent that some diseases have a familial tendency due to particular gene variants that elevate the risk of developing these conditions.

Recent studies have revealed that genetics can account for 40-70% of obesity. Over 50 genes, including the fat mass and obesity-associated gene (FTO), have been singled out as strongly linked to obesity.

These genes exert influence over various factors, such as:

• Levels of hunger
• Consumption of calories and the sensation of fullness (satiety)
• Regulation of eating behaviors
• Engagement in physical activity
• Storage of body fat

While external elements like dietary patterns and lifestyle choices undoubtedly contribute to obesity, a genetic predisposition can render certain individuals more vulnerable to excessive weight gain. This vulnerability is particularly evident when multiple family members share these genetic susceptibility factors, elevating the likelihood of obesity in families.

Given these findings, how exactly do genes contribute to the development of obesity?

Genetic Factors in Obesity

Genetic factors play a substantial role in the development of obesity. Research has revealed that obesity can have both monogenic and polygenic causes.

Monogenic obesity

This type of genetic obesity refers to cases where a single gene mutation leads to obesity. These mutations can be inherited in an autosomal dominant or autosomal recessive manner.

Examples of monogenic obesity include:

• Mutations in the leptin gene (LEP)
• Leptin receptor gene (LEPR)
• Proopiomelanocortin gene (POMC)
• Prohormone convertase 1 gene (PCSK1)
• Melanocortin 4 receptor gene (MC4R).

Polygenic obesity

This involves the interaction of multiple genes, each with relatively small effects. Genome-wide association studies (GWAS) have identified over 250 genes associated with obesity.

Notably, the FTO gene on chromosome 16 has been identified as a key contributor to the obesity phenotype and carries the highest risk.

Genetic Testing for Obesity

Currently, no commercially available genetic tests specifically target "obesity genes" to predict an individual's susceptibility to obesity.

Such tests' ethical and practical implications have sparked debates among healthcare professionals, public health researchers, and advocates within the fat-activist community.

Concerns include the potential for increased stigmatization of individuals with larger body sizes, not all individuals with "obesity genes" will develop obesity, and the absence of a definitive cure for obesity.

It is argued that regardless of genetic predisposition, the recommended treatment for obesity remains largely consistent.

New Treatments for Genetic Obesity

Precision Medicine and Personalized Treatments

Advancements in precision medicine have led to the development of novel and more effective treatments for genetic obesity. This approach focuses on personalized treatment plans tailored to an individual's genetic makeup and specific condition.

Unlike the traditional one-size-fits-all approach, precision medicine offers targeted interventions based on a deeper understanding of different types of obesity.

Targeting Misbehaving Genes

Researchers have made notable progress in developing medications that target specific genes contributing to obesity.

One such example is using GLP-1 agonists like Ozempic (semaglutide). These medications mimic appetite and food intake-regulating hormones to induce weight loss and manage diabetes.

The US Food and Drug Administration (FDA) approved Ozempic for chronic weight management in adults with obesity or overweight with weight-related conditions such as high blood pressure, type 2 diabetes, or high cholesterol.

Clinical trials have shown significant weight loss results, with participants losing an average of 12.4% of their initial body weight over one year.

Lifestyle Modification Therapies

Lifestyle modification remains a cornerstone of clinical management. Nutritional, behavioral, and exercise interventions led by trained health professionals are recommended.

Dietary control measures, such as establishing eating routines and limiting food access, can help manage hyperphagia – a condition characterized by excessive eating or an extreme appetite – and improve quality of life. Adapted physical activity is crucial, particularly in conditions like Prader-Willi syndrome (PWS) and pathogenic MC4R variants.

While studies have shown the positive effects of multicomponent lifestyle interventions on health outcomes, these interventions require ongoing vigilance and may be more effective when initiated early in childhood.

Bariatric Surgery for Genetic Obesity

Role of Bariatric Surgery

Bariatric surgery has emerged as a significant intervention for severe obesity, including cases with genetic and syndromic causes.

Common surgical techniques, such as sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), have shown sustainable weight reduction and remission of comorbidities in patients with common obesity.

Syndromic and Monogenic Obesity

In syndromic obesity, bariatric surgery has been considered for conditions like PWS. However, long-term outcomes are variable, with some studies indicating weight regain and limited success in maintaining weight loss.

Syndromic obesity patients may be more prone to surgical complications, given their complex behavioral and developmental challenges.

Genetic Factors and Bariatric Surgery

Genetic variants, particularly those affecting the melanocortin pathway, have been studied about bariatric surgery outcomes.

Heterozygous carriers of specific variants in the leptin-melanocortin pathway have shown mixed results regarding weight loss and long-term efficacy after surgical interventions. Some genetic variants may impact weight loss success and the weight potential regain.

Considering Surgical Interventions

While bariatric surgery remains an option for some individuals with genetic obesity, it is crucial to approach such decisions carefully. A multidisciplinary evaluation, including a thorough assessment of genetic factors and potential behavioral challenges, is essential before surgery.

Wrap-Up

Genetics do play a role in obesity, with numerous genes affecting things like metabolism and hunger regulation. However, lifestyle and diet choices have a bigger impact on the obesity epidemic.

While genetic predisposition can increase a person's risk of developing obesity, research shows that this genetic influence is not insurmountable. Regular physical activity has been found to be particularly effective in counteracting the effects of obesity-related genes. A study published in PLOS Genetics identified several types of exercise that can help offset genetic risk factors for obesity, with jogging showing the most significant benefits. For individuals with a higher genetic predisposition to obesity, maintaining an active lifestyle may be even more crucial. Engaging in at least 3-4 hours of moderate activity per day has been shown to significantly reduce the impact of obesity-related genes. This research underscores the importance of exercise in managing weight, especially for those with a family history of obesity. By adopting healthy lifestyle habits, individuals can take control of their weight management, regardless of their genetic makeup.

While certain genes might make weight gain easier, staying active and eating well can prevent obesity. It's important to remember that having certain genes doesn't guarantee obesity; healthy habits matter too.

FAQs on Genetic Obesity

What is an example of a genetic cause of obesity?

An example of a genetic cause of obesity is Prader-Willi syndrome (PWS), a genetic syndrome caused by chromosomal abnormalities. Individuals with PWS have central nervous system dysfunction, leading to abnormally increased appetite and early-onset obesity.

What is the genetic form of obesity?

The most common genetic form of obesity is Melanocortin 4 Receptor Deficiency (MC4R deficiency). Assessing the MC4R gene's sequence is increasingly important in evaluating severely obese children.

How is genetic obesity treated?

Genetic obesity is primarily managed through environmental control, starting early to prevent obesity progression and promote healthy eating and exercise habits.

Can you overcome genetic obesity?

Yes, you can. While genetics play a role, changing habits, lifestyle, and mindset can help you overcome genetic predispositions. Healthy eating, regular exercise, and long-term commitment are key.

What is the main cause of obesity?

Factors like diet and lifestyle choices primarily cause obesity. Consuming excessive processed or fast food high in fat and sugar, along with excessive alcohol consumption, contributes to obesity.