One of the most pressing health concerns of the 21st century is obesity. According to the WHO, 1 billion people worldwide are currently obese.
Some of the common reasons for obesity are poor lifestyle choices, like overeating, lack of exercise, sedentary lifestyle and junk food. These factors have a substantial role in obesity.
But do genes have any significant role in obesity? Research suggests that obesity is a complex interplay between genes, environment and lifestyle factors.
Is it true? Let’s find out. In this article, let’s understand whether obesity is genetic or not.
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Key Topics:
What is obesity?
In simple words, obesity is defined as “excessive fat accumulation in the body that presents a health risk. Clinically, obesity can be measured using the body mass index (BMI). BMI is a common screening tool to define and measure obesity, a simple calculation based on a person’s weight and height.
According to the WHO, a person with a BMI of 30 or above is considered to be obese. Obesity can result in serious health problems like type 2 diabetes, cardiovascular disease, certain cancers and joint disorders.
It occurs through the complex interplay between lifestyle, environment, and genetics. So, obesity is genetic and genes play a significant role here.
How does obesity occur?
We are not going to discuss the whole mechanism, but rather to understand the foundation. Let’s see how obesity occurs.
The imbalance between the energy intake and energy expenditure is the reason why obesity develops. Basically, it is a result of consuming calories more than required and not burning them.
So, when the body takes in more calories than it uses, the excess is stored as fat, leading to weight gain. Interestingly, a brain part known as the hypothalamus regulates all these activities, the signals for hunger, satiety and energy status.
Here, two key hormones provide signals to the command centre (hypothalamus) – leptin and ghrelin.
Fat cells secrete leptin, while the stomach secretes ghrelin and gives a signal to the brain to reduce appetite and increase energy expenditure, and hunger and food intake, respectively.
This entire system is controlled by hormones and catalysed by enzymes, hence regulated by genes.
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Genetics of obesity:
Obesity is genetic and controlled by genes. Recent studies showed that more than 1100 genomic loci are associated with either obesity directly or body mass index. Among these 127 gene loci are candidates and widespread.
Both the polygenic and monogenic types of obesity have been reported. However, polygenic obesity is more common. Meaning, multiple genes and associated pathways are disturbed simultaneously and make you fat.
Genes associated with obesity:
| Genes | Gene name | Role in Obesity |
| ADIPOQ | Adiponectin | Produced by fat cells, promotes energy expenditure and regulates glucose levels. |
| FTO | Fat mass and obesity associated genes. | Influences appetite and energy intake; variants increase the risk of higher BMI and obesity. |
| LEP | Leptin | A hormone produced by fat cells signals satiety to the brain and inhibits appetite. |
| LEPRe | Leptin receptor | A mutation in this gene can impair satiety signaling, causing severe obesity. |
| INSIG2 | Insulin-induced gene 2 | Regulates cholesterol and fatty acid synthesis. Variation in this gene is linked with a higher obesity risk. |
| MC4R | Melanocortin 4 receptor | Regulates appetite and energy homeostasis. And mutation here can cause early onset of obesity. |
| PCSK1 | Proprotein convertase subtilisin/kexin type 1 | Regulates insulin biosynthesis and hormone processing. Mutations lead to obesity and endocrine disorders. |
| PPARG | Peroxisome proliferator-activated receptor gamma | Stimulates fat cells development and lipid storage, variants linked to obesity and type 2 diabetes. |
| POMC | Pro-opiomelanocortin | A precursor for hormones regulating appetite, deficiency causes insatiable hunger and obesity. |
| SIM1 | Single-minded homolog | Mutations cause hyperphagia and obesity. |
| ADRB3 | Beta 3 adrenergic receptor | Controls fat breakdown in adipose tissues. Variation in ADRB3 can reduce fat burning and promote weight gain. |
Variations or mutations in certain genes can directly affect appetite control, metabolism, and fat storage.
For example, mutations in genes like LEP (Leptin) or LEPR (Leptin receptor) can disturb hunger and satiety regulation, while the MC4R variants destabilize appetite and energy homeostasis. Studies showed that the MC4R is the most common gene involved in causing obesity.
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Recent research studies:
Let us now understand the genetics behind obesity with the help of some well-studied research papers.
A review by Daley et. al. examines how genetics plays a significant role in several forms of obesity. Obesity is a result of polygenic factors and environment, but single gene mutations or syndromes can also be a major reason for some types of obesity.
The disruption in the leptin melanocortin pathway involving genes such as LEP, LEPR, MC4R, POMC, and PCSK1 can lead to early onset of obesity. Variations in these genes can produce hyperphagia and rapid weight gain.
Another study published in the International Journal of Molecular Sciences focuses on the genetic architecture of obesity. The study claims that while lifestyle and environmental factors contribute significantly, genetic variation also plays a crucial role in determining an individual’s susceptibility to weight gain.
Researchers highlight genes like FTO, MC4R, and LEPR, which regulate appetite, fat storage, and energy, are strongly associated with body mass index (BMI) and weight gain.
These genes are responsible for how the brain responds to hunger and satiety signals and how efficiently fat is metabolized in the body. The team concludes that obesity is a polygenic and multifactorial condition, which is shaped by complex gene-environment interactions.
For instance, people with certain genetic variants are predisposed to weight gain more easily when they expose themselves to a high-calorie diet and a sedentary lifestyle.
Interestingly, the FTO gene has been included in almost all the neutrigenomic testing modules as a candidate gene for obesity and type 2 diabetes assessment.
Can obesity be inherited?
Now the big question is, can obesity be inherited?
According to the research on twin and family studies, 40 to 70% of the variation in our genome is heritable. Meaning that the children of parents who are obese are significantly more likely to become obese.
And this is not just because of sharing the same environment or eating habits, but it is also because the child may have inherited mutant gene variants from the parent.
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Wrapping up:
In conclusion, genes have a pivotal role in obesity and associated lifestyle disorders. However, obesity is mainly polygenic and hence, any standard genetic test can not be used to determine the risk of predisposition.
Although it is not like other genetically inherited diseases. Obesity can be reversed by controlling and maintaining a healthy lifestyle. This also decreases the risk for other lifestyle diseases like type 2 diabetes or hypertension.
Understanding the role of genetics in obesity can help us explore a personalized approach for prevention and treatment.
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