Understanding Obesity: It’s More Than Just Food

Obesity is a complex, long-term disease that involves much more than just food choices; it is driven by a mix of genetics, hormones, and environmental factors [1, 2]. While often viewed as a "personal failure," science shows that biological systems in the brain and body strongly control how much we eat and how we store fat [3, 4].

The Role of Genetics

Most cases of obesity are polygenic, meaning hundreds of small genetic variations combine to increase a person's risk by making them feel hungry sooner or burn fewer calories at rest [4, 5]. However, there are rarer, more severe forms:

Monogenic Obesity: Caused by a mutation in a single gene (like MC4R or LEP), this often leads to extreme hunger and severe weight gain before the age of five [6-8].
Syndromic Obesity: This occurs alongside other clinical features, such as developmental delays or physical differences [6, 9]. Examples include Prader-Willi Syndrome and Bardet-Biedl Syndrome [6, 9, 10].

How Hormones Control Weight

The brain's hypothalamus acts as a control center, using hormones to balance hunger and energy [11, 12].

Leptin: Produced by fat cells, it signals the brain when the body has enough energy [13, 14]. Many people with obesity have leptin resistance, where the brain ignores this "full" signal, leading to constant hunger [13, 15, 16].
Ghrelin: Known as the "hunger hormone," it is produced in the stomach and tells the brain it is time to eat [12, 17].
Insulin: This hormone regulates blood sugar and fat metabolism [18]. Genetic variants can lead to insulin resistance, where the body stores fat more easily and is at a higher risk for type 2 diabetes [16, 18, 19].

Environmental and Lifestyle Factors

Genes "load the gun," but the environment "pulls the trigger" [20].

Stress and Cortisol: Chronic stress increases cortisol, a hormone that encourages the body to store fat in the abdominal (belly) area [21-23].
Sleep and Diet: Lack of sleep and diets high in processed sugars can disrupt hormonal balance, making weight loss much harder [23-25].
Physical Activity: Regular exercise can actually weaken the effect of certain weight-gain genes, such as the FTO gene [26-28].

When to See a Doctor

Clinicians look for "red flags" to determine if obesity has a genetic cause, including [29, 30]:

Severe weight gain before age 5.
Extreme, constant hunger (hyperphagia).
A strong family history of severe obesity.
Other issues like developmental delays or vision problems.

Precision Medicine: A New Approach

Because genetic obesity is biological, standard dieting often fails [31]. New targeted therapies, such as the drug setmelanotide, are now used to treat specific genetic defects in the appetite-control pathway [7, 32, 33]. This "precision medicine" approach focuses on fixing the underlying biological cause rather than just counting calories [1, 33].

 

References

Barber, T. M. (2022). Why are women with polycystic ovary syndrome obese? British Medical Bulletin, 143(1), 4–15. https://doi.org/10.1093/bmb/ldac007

Better Health Channel. (2016, June 4). Obesity and hormones. Department of Health, State Government of Victoria. https://www.betterhealth.vic.gov.au/health/healthyliving/obesity-and-hormones

Chamarthi, V. S., & Daley, S. F. (2025, September 15). Genetic and syndromic causes of obesity: Diagnosis and management. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK573068/

Farzand, A., Rohin, M. A. K., Awan, S. J., Ahmad, A. M. R., Akram, H., Saleem, T., & Imran, M. M. (2025). Nutrigenomics of obesity: Integrating genomics, epigenetics, and diet–microbiome interactions for precision nutrition. Life, 15(11), 1658. https://doi.org/10.3390/life15111658

Kim, J. H., & Choi, J. H. (2013). Pathophysiology and clinical characteristics of hypothalamic obesity in children and adolescents. Annals of Pediatric Endocrinology & Metabolism, 18(4), 161–167. https://doi.org/10.6065/apem.2013.18.4.161

Qi, L. (2014). Personalized nutrition and obesity. Annals of Medicine, 46(5), 247–252. https://doi.org/10.3109/07853890.2014.891802

van der Valk, E. S., Savas, M., & van Rossum, E. F. C. (2018). Stress and obesity: Are there more susceptible individuals? Current Obesity Reports, 7(2), 193–203. https://doi.org/10.1007/s13679-018-0306-y

Yeung, A. Y., & Tadi, P. (2023, January 3). Physiology, obesity neurohormonal appetite and satiety control. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK555906/