Learn effective strategies to overcome obesity for good. Explore the role of genetics, lifestyle changes, and sustainable habits on Meri Sehat.

From Genes to Jeans: How To Beat Obesity For Good

Obesity is defined as an excessive accumulation of body fat, typically measured using the Body Mass Index or BMI.

Introduction

Are you fat or are you obese? Is it due to your lifestyle or something more serious like an underlying cause &ndash; an illness or, perhaps, your genes? Can you ever overcome it or is it useless to even hope? Let&rsquo;s find out! 
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Understanding Link Between Genes And Weight

According to the World Health Organization (WHO), a BMI of 30 or higher classifies an individual as obese.

The global rise in obesity has turned it into a major public health issue. The WHO reports that the global prevalence of <a href="https://merisehat.pk/disease/obesity">obesity</a> has nearly tripled since 1975. As of 2021, over 650 million adults were classified as obese.<a href="#accordion">[1]</a>

It is associated with numerous health risks, including heart disease, diabetes, and certain cancers. What makes it complex is the fact that the condition is influenced by a variety of factors, the most important of which is genetics. 
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In layman&rsquo;s terms, a genetic predisposition means there is an increased likelihood of developing a particular disease or condition based on your genetic makeup. So, take obesity for instance, if certain genes are present in your DNA, then there is a higher chance you would be obese compared to someone without those genes.

Research indicates that genetics increases your risk for obesity by 40-70%; hence, its importance.<a href="#accordion">[2]</a> Your genes influence your metabolic rate, fat storage, appetite, and food preferences.

To date, around 250 genetic variants are associated with obesity.<a href="#accordion">[3]</a> These variants affect pathways related to energy balance, lipid metabolism, and the formation of fat cells. 
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<ul>
	<li>
	<h5>FTO Gene</h5>
	</li>
</ul>

The FTO gene is one of the most well-studied genetic contributors to obesity. Certain variants of the FTO gene increase the risk of obesity due to increased appetite and caloric intake.

A study found that individuals with two copies of the risk allele (variant) of the FTO gene weighed about 3 kg more than those without the risk allele.<a href="#accordion">[4]</a> 
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<ul>
	<li>
	<h5>LEPR Gene</h5>
	</li>
</ul>

Mutations in the LEPR gene can lead to leptin resistance, a condition where the brain does not respond to leptin signals, resulting in overeating and weight gain. 
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<ul>
	<li>
	<h5>MC4R Gene</h5>
	</li>
</ul>

The Melanocortin 4 Receptor (MC4R) gene plays a key role in regulating hunger and energy expenditure. Mutations in the MC4R gene are linked to severe obesity, starting in early childhood.

One study reported that individuals with MC4R mutations had significantly higher BMI and body fat percentages compared to those without the mutations.<a href="#accordion">[5]</a>

Generally, having a genetic predisposition doesn&#39;t guarantee that you will develop the condition; it simply means you are more susceptible to it. Environmental factors, lifestyle choices, and other variables also play a significant role in whether the condition actually manifests. It&rsquo;s like there&rsquo;s no escaping it if you&rsquo;re genetically inclined to obesity, but you can manage it by keeping other factors under control. 
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Changes in gene expression, without altering the DNA sequence, can be influenced by various environmental and lifestyle factors such as diet, physical activity, stress, and exposure to toxins. This is known as epigenetics.

Epigenetic modifications can turn genes on or off, affecting how cells function and how traits are expressed. 
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<ul>
	<li>
	<h5>Diet And Nutrition</h5>
	</li>
</ul>

Diet can significantly impact epigenetic markers. Diets high in fat and sugar can lead to increased fat storage and obesity.

Data suggests dietary patterns could influence DNA methylation, a key epigenetic mechanism that affects genes involved in metabolism and appetite regulation.<a href="#accordion">[6]</a> 
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<ul>
	<li>
	<h5>Physical Activity</h5>
	</li>
</ul>

Regular physical activity can induce beneficial epigenetic changes that improve metabolic health and reduce the risk of obesity.

Moreover, it could modify the expression of genes related to inflammation and energy expenditure, promoting healthy weight loss. 
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<ul>
	<li>
	<h5>Stress And Mental Health</h5>
	</li>
</ul>

Chronic stress can lead to epigenetic modifications that increase the risk of obesity by influencing hormones like cortisol, which regulates appetite and fat storage.

Stress management techniques, such as mindfulness and meditation, have shown promising results in reversing some of these epigenetic changes and supporting healthy weight loss efforts. 
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Understanding the genetic basis of obesity can lead to more personalized and effective weight loss strategies. Here are some approaches: 
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<ul>
	<li>
	<h5>Genetic Testing</h5>
	</li>
</ul>

Genetic testing can identify specific genetic variants associated with obesity. Once you understand your predisposition, you can tailor your weight loss plans accordingly. 
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<ul>
	<li>
	<h5>Dietary Adjustments</h5>
	</li>
</ul>

Personalized nutrition plans tailored to an individual&rsquo;s genetic makeup can enhance weight loss. For example, if you have the FTO gene variant, you may benefit from a higher protein diet to reduce appetite and increase satiety.

Or, if your epigenetic markers indicate a high sensitivity to dietary fats, a low-fat diet can help you in managing obesity.

A study found that personalized diets based on genetic profiles led to greater weight loss compared to standard diets.<a href="#accordion">[7]</a> 
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<ul>
	<li>
	<h5>Exercise Regimens</h5>
	</li>
</ul>

Similar to diet, genetics can also influence how your body responds to different types of exercise. Personalized exercise programs can maximize fat burning, muscle development, and overall fitness.

Integrating these insights into exercise prescriptions can enhance motivation and adherence to physical activity regimens. For example, the presence of epigenetic markers related to inflammation might allow your trainer to focus on low-impact exercises combined with anti-inflammatory diets. 
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<ul>
	<li>
	<h5>Behavioral Interventions</h5>
	</li>
</ul>

Behavioral strategies, such as cognitive-behavioral therapy and motivational interviewing, can be customized based on genetic predispositions to address overeating and improve adherence to weight loss plans. 
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<ul>
	<li>
	<h5>Medical And Pharmacological Treatments</h5>
	</li>
</ul>

Based on a specific genetic profile, your doctor may recommend certain medications and surgeries that would prove more effective for your weight loss. For instance, if you have leptin resistance, you may be prescribed leptin-mimetic drugs. 
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Conclusion

Innovations in genomic and epigenomic technologies are making it easier to analyze and interpret epigenetic data, paving the way for a more precise and personalized weight loss plan.

As the cost of testing decreases, these personalized approaches will become more accessible to a broader population and can be used to combat the obesity epidemic.

By considering individual genetic profiles, healthcare providers can develop more effective and sustainable weight management plans. Incorporating genetic testing, personalized nutrition, tailored exercise regimens, and customized behavioral interventions can significantly improve outcomes for individuals struggling with obesity. 
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Key Takeaways

<ul>
	<li>Genetics play a significant role in predisposing individuals to obesity, with heritability estimates ranging from 40-70%.</li>
	<li>Specific genes, such as FTO, MC4R, and LEPR, have been identified as influencing appetite regulation, metabolism, and fat storage.</li>
	<li>Epigenetic modifications, such as DNA methylation and histone acetylation, can alter gene expression related to obesity without changing the underlying DNA sequence.</li>
	<li>Lifestyle factors like diet, exercise, stress, and environmental exposures can influence epigenetic marks and impact susceptibility to obesity.</li>
	<li>Tailored interventions may include customized diet plans, exercise regimens, and behavioral modifications based on genetic profiles and epigenetic markers.</li>
	<li>Integrating genetic information into public health initiatives can improve obesity prevention and management strategies.&nbsp;</li>
</ul>

[1] Boutari C, Mantzoros CS. A 2022 update on the epidemiology of obesity and a call to action: as its twin COVID-19 pandemic appears to be receding, the obesity and dysmetabolism pandemic continues to rage on. Metabolism. 2022;133:155217.

[2] McPherson R. Genetic contributors to obesity. Can J Cardiol. 2007;23 Suppl A(Suppl A):23A-27A.

[3] Tirthani E, Said MS, Rehman A. Genetics and Obesity. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

[4] Frayling TM, Timpson NJ, Weedon MN, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007;316(5826):889-894.

[5] Adamska-Patruno E, Bauer W, Bielska D, et al. An Association between Diet and MC4R Genetic Polymorphism, in Relation to Obesity and Metabolic Parameters-A Cross Sectional Population-Based Study. Int J Mol Sci. 2021;22(21):12044. Published 2021 Nov 7.

[6] Smith ENL, Chandanathil M, Millis RM. Epigenetic Mechanisms in Obesity: Broadening Our Understanding of the Disease. Cureus. 2023;15(10):e47875. Published 2023 Oct 28

[7] Jinnette R, Narita A, Manning B, McNaughton SA, Mathers JC, Livingstone KM. Does Personalized Nutrition Advice Improve Dietary Intake in Healthy Adults? A Systematic Review of Randomized Controlled Trials. Adv Nutr. 2021;12(3):657-669.

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